Citation: Baldwin, H.;
Loebel-Davidsohn, L.; Oliver, D.;
Salazar de Pablo, G.; Stahl, D.; Riper,
H.; Fusar-Poli, P. Real-World
Implementation of Precision
Psychiatry: A Systematic Review of
Barriers and Facilitators. Brain Sci.
2022, 12, 934. https://doi.org/
10.3390/brainsci12070934
Academic Editor: David E. Fleck
Received: 28 June 2022
Accepted: 12 July 2022
Published: 16 July 2022
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brain
sciences
Review
Real-World Implementation of Precision Psychiatry: A
Systematic Review of Barriers and Facilitators
Helen Baldwin 1,2,*, Lion Loebel-Davidsohn 3, Dominic Oliver 1 , Gonzalo Salazar de Pablo 1,4,5,6 ,
Daniel Stahl 7 , Heleen Riper 8,9,10 and Paolo Fusar-Poli 1,2,11,12
1 Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies,
Institute of Psychiatry, Psychology & Neuroscience, King’s College London, 16 De Crespigny Park,
London SE5 8AF, UK; dominic.a.oliver@kcl.ac.uk (D.O.); gonzalo.salazar_de_pablo@kcl.ac.uk (G.S.d.P.);
paolo.fusar-poli@kcl.ac.uk (P.F.-P.)
2 National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley
National Health Service Foundation Trust, London SE5 8AF, UK
3 Department of Molecular Medicine, Faculty of Medicine and Surgery, University of Pavia, 27100 Pavia, Italy;
lion.loebeldavidsoh01@universitadipavia.it
4 Institute of Psychiatry and Mental Health, Department of Child and Adolescent Psychiatry, Hospital General
Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación
Sanitaria Gregorio Marañón, CIBERSAM, 28009 Madrid, Spain
5 Departent of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience,
King’s College London, London SE5 8AF, UK
6 Child and Adolescent Mental Health Services, South London and Maudsley National Health Service
Foundation Trust, London SE5 8AZ, UK
7 Biostatistics Department, Institute of Psychiatry, Psychology and Neuroscience, King’s College London,
London SE5 8AF, UK; daniel.r.stahl@kcl.ac.uk
8 Department of Clinical, Neuro and Developmental Psychology, VU University,
1081 HV Amsterdam, The Netherlands; h.riper@vu.nl
9 Department of Psychiatry, Amsterdam University Medical Centre (VUmc),
1081 HV Amsterdam, The Netherlands
10 Department of Psychiatry, Faculty of Medicine, University of Turku, 20700 Turku, Finland
11 OASIS Service, South London and Maudsley National Health Service Foundation Trust,
London SE11 5DL, UK
12 Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy
* Correspondence: helen.baldwin@kcl.ac.uk
Abstract: Background: Despite significant research progress surrounding precision medicine in
psychiatry, there has been little tangible impact upon real-world clinical care. Objective: To identify
barriers and facilitators affecting the real-world implementation of precision psychiatry. Method:
A PRISMA-compliant systematic literature search of primary research studies, conducted in the
Web of Science, Cochrane Central Register of Controlled Trials, PsycINFO and OpenGrey databases.
We included a qualitative data synthesis structured according to the ‘Consolidated Framework for
Implementation Research’ (CFIR) key constructs. Results: Of 93,886 records screened, 28 studies
were suitable for inclusion. The included studies reported 38 barriers and facilitators attributed to the
CFIR constructs. Commonly reported barriers included: potential psychological harm to the service
user (n = 11), cost and time investments (n = 9), potential economic and occupational harm to the
service user (n = 8), poor accuracy and utility of the model (n = 8), and poor perceived competence in
precision medicine amongst staff (n = 7). The most highly reported facilitator was the availability of
adequate competence and skills training for staff (n = 7). Conclusions: Psychiatry faces widespread
challenges in the implementation of precision medicine methods. Innovative solutions are required at
the level of the individual and the wider system to fulfil the translational gap and impact real-world
care.
Keywords: precision medicine; psychiatry; real-world implementation; systematic review;
barriers; facilitators
Brain Sci. 2022, 12, 934. https://doi.org/10.3390/brainsci12070934 https://www.mdpi.com/journal/brainsci
Brain Sci. 2022, 12, 934 2 of 25
1. Introduction
Precision medicine describes the tailoring of health care to an individual and their
unique biological, social, and/or environmental profile, or such tailoring across stratified
subgroups [1]. Precision medicine replaces the more outdated term ‘personalized medicine’
due to fears that the term could be misinterpreted to suggest that specific interventions
could be developed for each unique individual, which is not the case. Whilst these con-
cepts have existed in somatic medicine for decades, such as the practice of matching the
blood type of transfusion patients to the donor, it has been introduced in psychiatry only
recently [2]. Furthermore, recent advances in data-driven mental health care have offered
further promise of embedding precision medicine more firmly across mental health care
services [3–5], in the form of diagnostic (the probability that a particular condition is
present), prognostic (probability of particular outcomes), and prediction (forecasting the
response to specific interventions) models [6]. Indeed, demonstrable progress has already
been observed in the delivery of oncology [7] and cardiology [8] services, amongst other
fields of medicine. However, psychiatry is yet to observe similar translational success and
numerous criticisms have emerged [9–11].
Despite significant progress in the development and validation of clinical prediction
models across psychiatric research, few of these advances have been successfully imple-
mented into clinical practice. In fact, a recent systematic review reported that less than 1%
of individualized prediction models existing in psychiatric literature are considered for
actual implementation in real-world care [6]. This clear translational gap necessitates a
closer examination of implementation barriers. Whilst there are a range of informational,
regulatory and logistical barriers which impede the progress of precision medicine in gen-
eral [12–17], psychiatry may also pose distinct challenges in light of the phenomenological
complexity and heterogeneous nature of psychiatric conditions [3,18], the lack of estab-
lished pathophysiological pathways in psychiatry [3,19], and unique ethical considerations
associated with the historically complex socio-political perceptions and attitudes towards
mental illness and psychiatry [20,21]. These additional challenges necessitate the system-
atic identification of key factors that obstruct or promote the implementation of precision
psychiatry, to create an empirical framework in order to devise appropriate solutions at the
level of the individual, the organization and the wider system.
Aims
This current review aims to systematically examine the existing literature concerning
the key barriers to, and facilitators of, the implementation of precision psychiatry into
real-world clinical practice. As such, we aim to develop a framework of barriers and
facilitators, structured in accordance with the Consolidated Framework for Implementation
Research (CFIR), in order to inform the development of future precision medicine models
in psychiatry.
2. METHODS
2.1. Search Strategy and Selection Criteria
We conducted a PRISMA-compliant (Table S1: PRISMA 2020 Statement and Checklist)
systematic literature review, including a systematic search strategy (Methods S1) conducted
in Web of Science (including Web of Science Core Collection, KCI-Korean Journal Database,
MEDLINE, Russian Science Citation Index, and SciELO Citation Index), the Cochrane
Central Register of Controlled Trials, PsycINFO via Ovid, and the OpenGrey database up
to and including publication on 25 October 2020.
The review protocol (PROSPERO: CRD42020182595) aimed to identify relevant litera-
ture which reported an assessment of the factors affecting the real-world implementation
of precision psychiatry methods, defined as the application of any method encompassing
diagnostic, prognostic, or predictive models to estimate risk or outcomes at an individual-
(precision) or subgroup-level (stratified) [2]. There were no restrictions in place regarding
the types of predictors in use, and the final literature was clustered against predictors
Brain Sci. 2022, 12, 934 3 of 25
previously validated. The full inclusion and exclusion criteria are listed in Table 1. We also
considered literature which reported on the perspectives of a variety of key stakeholders;
this allowed us to gain a comprehensive and multidisciplinary assessment of barriers
and facilitators throughout all stages of implementation. Any implementation studies or
other primary research which featured a qualitative, quantitative or mixed-methods ex-
amination of barriers and/or facilitators were considered for inclusion. Given the extreme
paucity of actual implementation studies,6 we also considered studies for inclusion which
adopted a more hypothetical consideration of implementation (i.e., primary research which
involved stakeholder consultation on the proposed application of aspects of precision
psychiatry methods).
Table 1. Inclusion and exclusion criteria.
Inclusion Criteria Exclusion Criteria
(I) Consultation with key stakeholders
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protocol (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which reported an assessment of the factors affecting the real‐world implementation 
of precision psychiatry methods, defined as the application of any method encompassing 
diagnostic, prognostic, or predictive models to estimate risk or outcomes at an individual‐ 
(precision) or subgroup‐level (stratified) [2]. There were no restrictions in place regarding 
the  types of predictors  in use, and  the  final  literature was clustered against predictors 
previously validated. The  full  inclusion and exclusion criteria are  listed  in Table 1. We 
also considered  literature which reported on the perspectives of a variety of key stake‐
holders; this allowed us to gain a comprehensive and multidisciplinary assessment of bar‐
riers and facilitators throughout all stages of implementation. Any implementation stud‐
ies or other primary research which featured a qualitative, quantitative or mixed‐methods 
examination of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social care professionals 
 Service users and family members and/or caregivers 
 Policymakers 
 Research scientists 
 Local community members 
NA 
(II) Precision 
psychiatry 
approach 
 Diagnostic, predictive or prognostic models employ‐
ing a precision (or stratified) appr ach   
 Specific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
 Sociodemographic 
 Service use 
 Behavioural 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
 Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Health and social care professionals
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protocol (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which reported an assessment of the factors affecting the real‐world implementation 
of precision psychiatry methods, defined as the application of any method encompassing 
diagnostic, prognostic, or predictive models to estimate risk or outcomes at an individual‐ 
(precision) or subgroup‐level (stratified) [2]. There were no restrictions in place regarding 
the  types of predictors  in use, and  the  final  literature was clustered against predictors 
previously validated. The  full  inclusion and exclusion criteria are  listed  in Table 1. We 
also considered  literature which reported on the perspectives of a variety of key stake‐
holders; this allowed us to gain a comprehensive and multidisciplinary assessment of bar‐
riers and facilitators throughout all stages of implementation. Any implementation stud‐
ies or other primary research which featured a qualitative, quantitative or mixed‐methods 
examination of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social care professionals 
 Service users and family members and/or caregivers 
 Policymakers 
 Research scientists 
 Local comm nity members 
NA 
(II) Precision 
psychiatry 
approach 
 Diagnostic, predictive or prognostic models employ‐
ing a precision (or stratified) approach   
 Specific to  he field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
 Sociodemographic 
 Service use 
 Behavioural 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
 Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Service users and family members and/or
caregivers
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protocol (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which reported an assessment of the factors affecting the real‐world implementation 
of precision psychiatry methods, defined as the application of any method encompassi  
diagnostic, prognostic, or predictive models to estimate risk or outcomes at an individual‐ 
(precision) or subgroup‐level (stratified) [2]. There were no restrictions in place regarding 
the  types of predictors  in use, and  the  final  literature was clustered against predictors 
previously validate . The  full  inclusion and exclusion criteria are  listed  in Table 1. We 
also considered  literature which reported on the perspectives of a variety of key stake‐
holders; this allowed us to gain a comprehensive and multidisciplinary assessment of bar‐
riers a d facilitators through ut all stages of implementation. Any implementation stud‐
ies or other primary research which feature  a qualitative, quantitative or mixed‐methods 
examinati n of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies f r inclusion 
which adopted a more  ypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social care professionals 
 Service users and family members and/or caregivers 
 P licymakers 
 Research scientists 
 Local community members 
NA 
(II) Precision 
psychiatry 
approach 
 Diagnostic, predictive or prognostic m dels  mploy‐
ing a  recision (or stratified)  pproach   
 Specific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
Clinical 
ociodemographic 
S rvice  se 
ehaviou al 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
Conference  bstracts b 
 Full journal articles 
Pro cols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Policym kers
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protocol (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which reported an assessment of the factors affecting the real‐world implementation 
of precision psychiatry methods, defined as the application of any method encompassi  
diagnostic, prognostic, or predictive models to estimate risk or outcomes at an individual‐ 
(precision) or subgroup‐level (stratified) [2]. There were no restrictions in place regarding 
the  types of predictors  in use, and  the  final  literature was clustered against predictors 
previously validate . The  full  inclusion and exclusion criteria are  listed  in Table 1. We 
also considered  literature which reported on the perspectives of a variety of key stake‐
holders; this allowed us to gain a comprehensive and multidisciplinary assessment of bar‐
riers a d facilitators through ut all stages of implementation. Any implementation stud‐
ies or other primary research which feature  a qualitative, quantitative or mixed‐methods 
examinati n of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies f r inclusion 
which adopted a more  ypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 He lth and social care professional  
 Service users and family members and/or caregivers 
 P licymakers 
Research scientists 
 Loc l commu ity members 
NA 
(II) Precision 
psychiatry 
approach 
 Diagnostic, predictive or prognostic models employ‐
ing a precision (or stratified) approach   
 Specific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
Clin al 
Sociodemographic 
S rvice use 
 Behavioural 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
 Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  n n‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
typ  
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Research scientists
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protoc l (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which reported an ass ssment of the factors affecting the real‐world impl mentation 
of precision psychiatry methods, defin d as the application of any method encompassing 
diagnostic, prognostic, or predictive models to estimate risk or outcomes at an individual‐ 
(precision) or subgroup‐l vel (stratified) [2]. There were no restrictions in place r garding 
the  types of predictor   in use, and  the  final  literature was clustered  gain t predictors 
previously validated. The  full  inclusion and exclusio  criteria are  listed  in T ble 1. We 
al o c nsidered  literature which reported on the persp ctives of a  ariety of key stake‐
holders; this allowed u  to gain a comprehensiv  and multi isciplinary assessm t of bar‐
ri rs and facilitators throughout all stages of implementatio . Any implementation stud‐
ies or other prim ry research which feature  a qualitative, quantitative or mixed‐ ethods 
ex mination of barriers  nd/ r  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social care professionals 
 Service users and family members and/or caregivers 
 Policymakers 
Research scientists 
 Loc l commu ity members 
NA 
(II) Precision 
psychiatry 
approach 
 Di stic, predictive or prognostic models employ‐
ing a precision (or stratified)  pproach   
 Specific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predicto s 
Clin al 
ociodemographic 
rvice  se 
ehaviou al 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  consider  actual  or 
proposed impl mentati n 
 Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  n n‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
typ  
Conference  bstracts b 
 Full journal articles 
Pro cols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
) evel  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Local community members
NA
(II) Precision psychiatry approach
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The revi w protocol (PROSPERO: CRD42020182595) aimed to identify releva  liter‐
ature which reported an assessment of the factors affe ting the real‐world imple entat on
of precis on psychiatry methods, d fine  a he application  f any method e compassing
diagn stic, prognostic, or predictive models to estimate risk or outc mes at an individual‐
(precision) or subgro p‐level (stratified) [2]. There were no restrictions in place regarding
th   types of predictors  in use, and  the  final literature was clustered aga st pr dictors
previously valida d. Th   full  inclusion and exclusion criteria are  listed  in Table 1. We 
also considered  lit rature which report d on the perspectives of a variety of key stake
holders; this allowed us to  ain a comprehens ve and mul disciplinary assessment of bar
riers and facil tators throug out all st ges of implementation. A y  mple entation stu ‐
ies or other primary r search which fe ed a qualitativ , quantitative or mixed‐methods 
examin tion of b rriers an /or  facil tators w re considered  for  inclusion. Given  the ex‐
treme paucity of actual implem ntation stu ies,6 we also considered studi s fo  inclusion 
whi  adopted a more hypothetical  consideration of implementation  ( .e., primary  re‐
search which involved s akeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion  riteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and  ocial c re prof ssionals 
Service users and family members and/or caregivers 
Policymakers 
Research sc e tists 
 Local community members 
NA 
(II) Pre is on 
psychiatry 
approach 
Diagnos ic, predictive or prognost c models employ‐
ing a precision (or stratified) approach   
pecific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
 ociod mogr phic 
 Service use 
Behavio ral 
Bio rkers  ( uroim ging,  genomic,  phar‐
macogeno ic, metabol mic, cognitive) 
Any combinatio  of  he above 
NA 
(IV) Study design 
 P imary  r search  stud s which  co sider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Se ondary  research  (system
atic  nd  n n‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  b r iers/ 
facilitators 
 Systematic asse sment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers a d/or
fac litators only  raised  in  the 
discussion section 
( I) Publication 
typ  
 Conference abstracts b 
 Full journal articles 
Protocols 
d torials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level and 
quality of  v‐
idence 
  level or quality of evidence   
(VIII) Language   Any language  NA 
Diagn stic, predictive or prognostic m dels
employing a precision (or stra ifi d) approach
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30 
The review protoc l (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which reported an ass ssment of the factors affecting the real‐world impl mentation 
of precision psychiatry methods, defin d as the application of any method encompassing 
diagnostic, prognostic, or predictive models to estimate risk or outcomes at an individual‐ 
(precision) or subgroup‐l vel (stratified) [2]. There were no restrictions in place r garding 
the  types of predictor   in use, and  the  final  literature was clustered  gain t predictors 
previously validated. The  full  inclusion and exclusio  criteria are  listed  in T ble 1. We 
al o c nsidered  literature which reported on the persp ctives of a  ariety of key stake‐
holders; this allowed u  to gain a comprehensiv  and multi isciplinary assessm t of bar‐
ri rs and facilitators throughout all stages of implementatio . Any implementation stud‐
ies or other prim ry research which feature  a qualitative, quantitative or mixed‐ ethods 
ex mination of barrier   nd/ r  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of  ctual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search whi h involved stakehold  consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consult tio  
with  key 
stakeh lders 
 Health and social car  professionals 
 Service users and family memb rs  nd/or caregivers 
Policymakers 
R sear h sc e t sts 
 Loca  community members 
NA 
(II) Precision 
psychiatry 
approach 
Diagnos ic, predictive or prognost c models employ‐
ing a precision (or stratified)  pproach   
pec fic to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
Clinical 
o i d mographic 
S rvi e use 
ehaviou al 
Bio rkers  ( euroim ging,  genomic,  phar‐
macogeno ic, metabol mic, cognitive) 
Any combinatio of  he above 
NA 
(IV) Study design 
Primary  r search  studi s which  consider  actual  or 
proposed impl mentati n 
 Qualitative, quantitative or mixed methods   
 Secondary research  (system‐
atic  nd  n n‐systematic  re‐
views, and meta‐analyses) a 
(V) Ass ssment 
of  b rriers/ 
facilitators 
 Systematic assessment of barriers and/or facilitators 
to pr cision (or stratified) psychiatry 
 Ass ssment of barriers and/or 
fac litators  only  raised  in  the 
discussion section 
( I) Publication 
typ  
Conference  bstracts b 
Full journal articles 
Pro cols 
ditorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of  v‐
idence 
  level or quality of evidence   
(VIII) Language   Any language  NA 
Specific t th field of psychia ry (i.e., any
DSM/ICD diagnosis)
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protocol (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
atur  which reported  n as ssme t of the factors affecting the real‐world implementation 
f precision psychiatry methods, d fine  as the application of any method encompassing 
diagnostic, prognostic, or pre ictive mo els to estimate risk or outcomes at an individual‐ 
(pr cision) or subgroup‐leve  (stratified) [2]. There were no restrictions in place regarding 
the types  f predictors  in us , and  the  fin l  literature was clustered against predictors 
pr iously validated. The  full  inclusi  and exclusion criteria are  listed  in Table 1. We 
also co sidered  literature which reported  n the perspectives of a variety of key stake‐
holders; this allowed us to gai  a compr hensive and multidisciplinary assessment of bar‐
riers a d facilitat rs through ut all stag s of implementation. Any implementation stud‐
ies or  ther primary r s arch which featured a qualitative, quantitative or mixed‐methods 
examinati n of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity  f actual impleme tation studies,6 we also considered studies for inclusion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakehold r consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social care professionals 
 Service users and family me bers and/or caregivers 
 Policymakers 
 R search scientists 
 Local community me bers 
NA 
(II) Precisio  
psychiatry 
a proach 
 Diagnostic, predictive or pr gnostic models employ‐
ing a precision (or strat fied) approach   
 Specific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Pr d tors 
 Clinical 
 Sociodemographic 
 Service use 
 Behavioural 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
 Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  consi er  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  ba riers/ 
facilitators 
 Systematic assessment of barriers and/or facilitators 
to precision (or str tified) psychiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Precision models relating to trau atic brain
injury, neurological disord rs r dementias
(III) Predictors
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The revi w protoc  (PROSPERO: CRD42020182595) aimed to identif  relevant liter
ature which report  an ass sment of the f ctors affecting the real‐wo ld  mpl nta ion
of precision psychiatry m t ds, defin d  s the applica ion of ny method  compa sing 
diagn stic, ognostic, or predictive models to estim e risk or outcome  at   individual
(precision) or su g o p‐l vel (str t f ed) [2]. Th re were no rest iction   n place r garding 
he  ty es of predictor   in use, and  the final  literatur  was clus d  gain  predictors
previously validated. The  full  in lusion and exclusi  criteria are  listed  in T ble 1. We 
al o c nsidered  literature w ich repor ed on the pers ctive of a  ariety of key stake
hold rs; thi  allowed u   o gain a comprehen iv and multi i ciplin y ass sm  of bar‐
ri rs and facilitators throughout all stages of i pleme tatio . A y implementation stud
i s or other pr m ry research which feat re  a quali at ve, quantit tive or mixed‐ ethods 
ex mination of ba rier   n / r  facilitators were consid red for  inclusi n. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for i clusion 
w ich ad pted a more hypothetic l  consideration of  implementati n  (i.e., primary  re‐
search which  volved stakeho d  c nsultat on on the proposed application of aspects of 
precision psychia ry met ods). 
Table 1. Inclusion and exclusion criteri . 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeh lders 
 Health and social ca e professionals 
Service users and family memb  and/or caregivers 
 Policymakers 
Research scientists 
 Local co munity member  
NA 
(II) Precision 
psychiat y 
approach 
Diagnostic, predictive or prognostic models employ‐
ing a precision (or stratified) approach   
 Specific t  the field of p ychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
 Sociodemographic 
 Service use 
Behavioural 
 Bi markers  (neuroimaging,  genomic,  phar‐
macogenomic, metabol mic, cognitive) 
 Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  co sider  actu l  or 
proposed impl mentati n 
 Qualitative, quantitative or mix d methods   
 Secondary  research  (system‐
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
) Assessme t 
of  barriers/ 
facilitat rs 
Systematic assessment of barriers and/or facilitators 
to pr cision (or stratified) psychiatry 
Assessment of barriers and/or 
f c litators  only  raised  in  the 
discussion section 
( I) P blication 
type 
Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Clinical
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The revi w protocol (PROSPERO: CRD42020182595) aimed to identif  relevant liter
ature which report  an assessment of the factors affecting the real‐world implementation 
of precision psychiatry met ds, defined as the applica ion of any method  compa sing 
diagn stic, ognostic, or predictive models to estim e risk or outco es at an individual‐
(precision) or su g oup‐level (str t f ed) [2]. Th re were no rest iction   n place regarding 
he  ty es of predictors  in use, and  the final  literature was clust red against predictors
previously validated. The  full  inclusion and exclusi n criteria are  listed  in Table 1. We 
also considered  literature w ich reported on the pers ectives of a variety of key stake‐
holders; thi  allowed us  o gain a comprehensive and multidisciplinary assessment of bar‐
riers and facilitators throughout all stages of implementation. Any implementation stud‐
ies or other primary research which featured a qualitative, quantitative or mixed‐methods 
examination of barri rs and/o   facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social care  rofessionals 
Service users and family members and/or caregivers 
Poli ymakers 
Research sc e tists 
 Local co munity members 
NA 
(II) Precision 
psychiatry 
approach 
Diagnos ic, predictive or prognost c models employ‐
ing a precision (or stratified) approach   
pe ific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
 Sociode ographic 
 ervice use 
Behavioural 
Bi rkers  ( euroim ging,  genomic,  phar‐
macogeno ic, metabol mic, cognitive) 
Any combinatio  of  he above 
NA 
(IV) Study design 
Primary  r search  studi s which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  nd  n n‐systematic  re‐
views,  nd meta‐a alyses) a 
) Assessme t 
of  b rriers/ 
facilitat rs 
Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
Assessment of barriers and/or 
f c litat rs  only  raised in  the 
discussion section 
( I) P blication 
typ  
Conference abstracts b 
 Full journal articles 
Protocols 
ditorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of  v‐
idence 
  level or quality of evidence   
(VIII) Language   Any language  NA 
ociode ographic
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protoc l (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which reported an ass ssment of the factors affecting the real‐world impl mentation 
of precision psychiatry methods, defin d as the application of any method encompassing 
diagn stic, prognostic, or predictive models to estimate risk or outco es at an individual‐ 
(precision) or subgro p‐l vel (stratified) [2]. There were no restrictions in place r garding 
the  types of predictors  in use, and  the  final  literature was clustered  gain t predictors 
previously validated. The  full  inclusion and exclusio  criteria are  listed  in T ble 1. We 
al o c nsidered  literature which reported on the persp ctives of a  ariety of key stake‐
holders; this allowed us to gain a comprehensiv  and multi isciplinary assessm t of bar‐
ri rs and facilitators throughout all stages of implementatio . A y implementation stud‐
ies or other prim ry research which feat re  a qualitative, quantitative or mixed‐ ethods 
ex mination of barri r   n /   facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual i plementation studies,6 we also considered studies for inclusion 
w ich ad pted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakehold  c nsultat on on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeh lders 
 Health and social ca e  rofessionals 
 Service users and family members and/or caregivers 
Poli ymakers 
Research scientists
 Loc l community members 
NA 
(II) Precision 
psychiat y 
approach 
Diagnostic, predictive or prognostic models employ‐
ing a precision (or stratified)  pproach   
 Specific t  the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
III) Predictors 
Clinical 
ociod ographic 
S rvice  s  
eh viou al 
 Biomarkers  ( euroimaging,  genomic,  phar‐
macogenomic, metabol mic, cognitive) 
Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  co sider  actual  or 
proposed impl mentati n 
 Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  non‐systematic  re‐
views,  nd meta‐a alyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
Systematic assessment of barri rs and/or facilitators 
to pr cision (or stratified) psychiatry 
 Assessment of barriers and/or 
facilitat rs  only  raised in  the 
discussion section 
( I) Publication 
type 
Conference  bstracts b 
 Full journal articles 
Pro cols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
ervic use
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The revi w protocol (PROSPERO: CRD42020182595) aimed to identif  releva t liter
ature w ich report  an  ssessment of the factors  ffecting the real‐world i plementation 
of precision psychiatry met ods, defined as the applica ion of any meth d  compa si  
diagn stic, ognostic, or pr dictive models to estim  risk or outco es at an indivi ual‐
(pre ision) or su g oup‐level (str t f ed) [2]. Th re were no r st iction   n place reg ding 
he  ty es of predictors  in use, and  the final  literature w s clust red agai st predictors
viously valid te . The  full  inclusion and exclusi n crite ia are  listed  in Table 1. We 
also considered  literature w ich reported on the pers ectives of a variety of key stake‐
hold rs; thi  allowe  us  o gain a comprehensiv  and multidisciplinary ass ssment of bar‐
riers a d facilitators throughout all stages of implementation. Any im lement tion stud‐
ies or other primary research which feature    qualitative, quantitative or mixed‐methods 
examination of barri rs and/o   facilitators w re considered  for  inclusion. Given  the ex‐
treme paucity of  ctual i plementation studies,6 we also considered studies f r inclusion 
w ich ad pt d a more hypothetical  consider tion of  implementation  (i.e., primary  re‐
search whi h involved stakeholder c n ultat on on th  proposed application of aspects of 
p ecision psychi try methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social ca e professionals 
 Servi e users and family members and/or caregivers 
P li ymakers 
Resear h sc e t sts
 Local co munity membe s 
NA 
(II) Precision 
psychiat y 
approach 
Diagnostic, predictive or prognostic models employ‐
ing a precision (or stratified)  pproach   
pec fic t  the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
III) Predictors 
Cli ical 
o i d ographi  
S rvi e  s  
ehavi u al 
Bio rkers  ( euroimaging,  genomic,  phar‐
macogeno ic, metabol mic, cognitive) 
Any combinatio of  he above 
NA 
(IV) Study design 
 Primary  research  studies which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary  esearch  (system‐
atic  nd  non‐systematic  re‐
views,  nd meta‐a alyses) a 
(V) Assessment 
of  b rriers/ 
facilitat rs 
 Systematic assessment of barri rs and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers and/or 
fac litat rs  only  raised in  the 
discussion section 
( I) Publication 
type 
Conference  bstracts b 
 Full journal articles 
Pro cols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
ehavioural
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The revi w protocol (PROSPERO: CRD42020182595) aimed to identif  releva t liter
ature w ich report  an  ssessment of the factors  ffecting the real‐world i plementation 
of precision psychiatry met ods, defined as the applica ion of any meth d  compa si  
diagn stic, ognostic, or pr dictive models to estim e risk or outcomes at an individual‐
(pre ision) or su g o p‐level (str t f ed) [2]. Th re were no r st iction   n place reg ding 
he  ty es of predictors  in use, and  the final  literature was clust red agai st predictors
viously valid te . The  full  inclusion and exclusi n criteria are  listed  in Table 1. We 
also considered  literature w ich reported on the pers ectives of a variety of key stake‐
hold rs; thi  allowe  us  o gain a comprehensive and multidisciplinary assessment of bar‐
riers a d facilitators through ut all stages of implementation. A y implem nt tion stud‐
ies or other primary research which feat re  a qualitative, quantitative or mixed‐methods 
examinati  of barriers an /or  facilitato s were considered  for  inclusion. Given  the ex‐
tre e paucity of actual implementation studies,6 we also considered studies f r inclusion 
w ic  ad pted a more  ypothetical  consideration of  implementation  (i.e., primary  re‐
search whi h involved  takeholder c nsultat on on the proposed applic tion of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social ca   rofessionals 
 Servi e users and family members  nd/or care ivers 
 P licymakers 
R search scientists 
 Loc l co mu ity members 
NA 
(II) Precision 
psychiatry 
approach 
 Diagnostic, predictive or pro nostic models em loy
ing a precision (or stratified)  pproach   
 Sp cific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
Clin al 
 ociodemographic 
S rvice  se 
ehaviou al 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabol mic, cognitive) 
Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  co sider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary research  (system‐
atic  and  n n‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitat rs 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Ass ssment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
( I) Publication 
typ  
Conference  bstracts b 
Full journal articles 
Pro cols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
iomarkers (neuroimaging, geno ic,
pharmacogenomic, metabolomic, cognitive)
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30 
The review protoc l (PROSPERO: CRD42020182595) aimed to identify releva t liter‐
ature w ich reported an  ss ssment of the factors  ffecting the real‐world i pl mentation 
of precision psychiatry methods, defin d as the application of any meth d encompassi  
diagnostic, prognostic, or pr dictive models to estimate risk or outcomes at an individual‐ 
(pre ision) or subgroup‐l vel (stratified) [2]. There were no r strictions in place r g ding 
the  types of predictor   in use, and  the  final  literature was clustered  gai t predictors 
viously valid ted. The  full  inclusion and exclusio  criteria are  listed  in T ble 1. We 
al o c nsidered  literature which reported on the persp ctives of a  ariety of key stake‐
hold rs; this allowe  u  to gain a comprehensiv  and multi isciplinary assessm t of bar‐
ri rs a d facilitators through ut all stages of implementatio . Any implementation stud‐
ies or other prim ry research which feature  a qualitative, quantitative or mixed‐ ethods 
ex mination of barriers  nd/ r  facilitators wer  co sidered  for  inclusion. Given  the ex‐
treme paucity of actual i plementation studies,6 we also considered studies f r inclusion 
which adopted a more  ypothetical  consideration of  implementation  (i.e., primary  re‐
search whi h involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  In lusion C iteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social car   rofessionals 
 ervi e users and family members  nd/or caregivers 
 P licymakers 
R search scientists
Loc l commu ity members 
NA 
(II) Precision 
psychiatry 
approach 
Di stic, predictive or prognostic models employ‐
ing a precision (or stratified)  pproach   
Specific t  the field of psychiatry (i.e., any DSM/ICD
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
III) Predictors 
Clin al 
ociod mographic 
S rvice  s  
eh viou al 
 Bio arkers  (neuroimaging,  genomic,  phar‐
macogeno ic, metabol mic, cognitive) 
Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  consider  actual  or 
proposed impl mentati n 
Qualitative, quantitativ  or mixed methods   
Secondary research  (system‐
atic  and  n n‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
 Systematic assessment of barri rs and/or facilitators 
to precision (or stratified) psychiatry 
 Ass ssment  f b rriers and/or 
facilitators  only  raised  in  the 
discussion section 
) Publication 
typ  
Conference  bstracts b 
Full journal articles 
Pro cols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
) evel  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Any co bination of the above
NA
(IV) Study design
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30 
The revi w protoc l (PROSPERO: CRD42020182595) aimed  o  d ntify releva  liter
ature which eported an ss ssment of the factors affe ting the real‐world impl entat on
of pr cis on psychiatry methods, d f n  a he application  f any me hod e compas ng
diagnostic, prognostic, or predictive models to estimate risk or outc mes at an individual
(pre ision) o  subgroup‐l v l (stratified) [2]. There were n  re trictions in place r garding
th   types of predictor   in use, and  the  final literature was clustered  ga t pr dicto s
previously valida d. Th   full  inclusion and exclusio  criteria are  listed  in Table 1. We 
al o c nsidered  lit rature which  eport d on the persp ctives of a  ariety of key stake
holders;  his allowe  u  to  ain a comprehens v  and mul isciplinary assessm t of bar
ri rs and facil tators throug out all st ges of implementatio . Any  mple nt tion stu ‐
ies or other prim ry r search which fe u e  a qualitativ , quantitative or mixed‐ ethods 
ex min tio  of b rrier   nd/ r  facil tators w re considered  for  inclusion. Given  the ex‐
tre e paucity of  ctual i ple ntation stu ies,6 we also considered studi s fo inclusion 
w i  ad pted a more hypothetical  consideration of imple entation  ( .e., primary  re‐
search which involved s akehold  c nsultat on on the proposed application of aspects of 
precis on psych atry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeh lders 
Health and  ocial c e  rof ssionals 
Service users and family members and/or car givers 
 P licymakers 
Rese r h sc e t sts 
 Local com unity members 
 
(II) Pre is on 
psychiat y 
a proach 
Diagn s ic, predictive or pro nost c models em loy‐
ing a precision (or stratified) approach   
pec fic to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or de entias 
(III) Predicto s 
 linical 
oci d mographic 
ervi  use 
Behaviou al 
Bio rkers  ( uroim ging,  genomic,  phar‐
macogeno ic, metabol mic, cognitive) 
Any combinatio  of  he above 
NA 
(IV) Study design 
P imary  r search  stud s which  consider  actual  or 
proposed impl mentati n 
 Qualitative, quantitative or mixed methods   
 Se ondary  research  (system
tic and  n n‐systematic  re‐
views, and meta‐analyses) a 
( ) Assessment 
of  b r iers/ 
facilitators 
 Systematic asse sment of barriers and/or facilitators 
to pr cision (or stratified) psychiatry 
 Assessment of barriers a d/or
fac litators only  raised  in  the 
discussion section 
( I) Publication 
typ  
 Conference abstracts b 
 Full journal articles 
 Protocols 
d torials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level and 
quality of ev‐
idence 
  level or quality of evidence   
(VIII) Language   Any language  NA 
rimary search studies which con ider a tual or
proposed impl m ntation
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The rev w protocol (PROSPERO: CRD42020182595) aimed  o  d tify releva t liter
tu e w ich  por d an ss ssment  f the f ctors  ff cting th  real‐world  plemen ation
of pr cision psychiatry methods, def ned as the application o  any me d encompas ng
diagnostic, prognostic, or pr dictive models to estimate risk o outco es at a   ndivid al  
(pre ision) or subgroup‐lev l (stratified) [2]. There were n  r r c ons in place reg ding
th   types  f predictors  in use, and  the  final  liter ture was clust red agai st predictors 
viously valid ted. The  full  inclusion an  exclusion criteria a   liste   in T ble 1. We
lso con idere   literature which eported on the perspectives of   variety of key stak
hol rs; this allowe  us  o gain   comp eh nsiv  a d multidisciplinary  ssessment of bar‐
rie s  nd facilitato s throughout all stages of implementation. Any implementation stud‐
i s or oth r primary re earch which featur d a qualitative, quantitative or mixed‐methods 
exa ination of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
tr me paucity of  ctual implementation studies,6 we also considere   tudies for inclusion 
which adopted a  re hy othetical  consideration of  implem ntation  (i.e., primary  re‐
search w i h involved stakeholder consultation on the proposed application of aspects of 
precis on psych atry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Cr te ia  Exclusion Criteria 
) Consultation 
with  key 
stakeholders 
Health and social car   ofessionals 
 Servi e users a d family members  nd/or caregivers 
Policymakers 
Resea h sc e t sts 
Local community members 
 
(II) Precision 
syc iatry 
approach 
 Diagnos ic, predictive or prognost c models empl y‐
ing a precision (  str tified)  pproach   
pec f c to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
Precision  mod ls  relating  to 
traumatic brain  injury, neu o
logical disorders or dementias 
II Pre ictor  
Clinical 
ci d ographic 
rvi e  s  
ehaviou al 
Bio rkers  ( euroim ging,  genomic,  phar‐
macogeno ic, metabol mic, cognitive) 
Any combinatio of  he above 
NA 
(IV) Study design 
Primary  r search  studies which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary research  (system‐
atic  and  non‐systematic  re‐
views, and meta‐a alyses) a 
( ) Assessment 
of  b rriers/ 
facilitators 
Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Ass sment of barriers and/or 
fac litators  only  raised  in  the 
discussion section 
( I) Publication 
typ  
Conference  bstracts b 
Full journal articles 
 Pro cols 
ditorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
  level or quality of evidence   
(VIII) Language   Any language  NA 
Qualitative, qua tit tive or mixed methods
Br in Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review prot col (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ture which rep rted a   ssess ent of the f ctors affecting the real‐world implementation 
of precision psych try methods, defin d as the application of any method encompassing 
diagnostic,  rogno tic, or predictive  odels to estimate risk or outcomes at an individual‐ 
(precisi ) or subgroup‐level (stratified) [2]. There were no restrictions in place regarding 
th   types of predictors  n  se, a d  the  final  literature was clustered against predictors 
previ usly  alidate . The  full  i clusion an  exclusion criteria are  listed  in Table 1. We 
also considered  lit ature which repor d on the perspectives of a variety of key stake‐
holders; thi  all we  us t  gain a c mprehensive and multidisciplinary assessment of bar‐
ri s and facilitators throughout all stages of implementation. Any implementation stud‐
ies o  other  rimary research which featured a qualitative, quantitative or mixed‐methods 
examination of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusio  criteri . 
  Inclusion Criteria  Exclusion Crite ia 
(I) Consultation 
with  key
st ke olde s 
 Health and socia  care professionals 
 S rvice users and family me bers and/or caregivers 
 Policymakers 
 Research scientists 
 Local community members 
NA 
(II) Precision 
psychiatry 
appr ach 
 Diagnostic, predictive or pr gnostic models employ‐
ing   precision (or stratified) approach   
 Specific to the field of psychiatry (i. ., any DSM/ICD 
di gnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Pred ctors 
 Clini al 
 Sociodemogr p ic 
 Service use 
 Behavioural 
 Biomarkers  (neuroimaging,  genomi ,  phar‐
macogenomic, metab l mic, cognitive) 
 Any combination of  he  bov  
NA 
(IV) Study des gn 
 Pr m ry  research  studies which  consi er  actual  or 
proposed implem ntation 
 Qualitative, quantita ive  r mixed m thods   
 Secondary  research  (system‐
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
 Systematic assessmen   f barri an / r facilitators 
to precision (or stratified) psych atry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idenc  
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
S condary research (systematic and
non-systematic reviews, and meta-analyses) a
(V) Assessment of barriers/ facilitators
Brain Sci. 2022, 12, x FOR PEER REVIEW  3 of  30  
The revi w protocol (PROSPERO: CRD42020182595)  ime   o  d ntif  relev t lit r
ature which report   n ssessment of the fact rs aff ting the real‐world  mple entat
of pr cis on psychiatry met ds, d f ne  a he applica ion  f any me h d compa ng
di gn stic,  ognostic, or predictive models t  estim e risk  r outc es at an individual
(pre ision) or su group‐lev l (str tified) [2]. Th re were n  re t iction  in place regarding
h   ty es of pred ctors  in use, and  the  final literature was clust red aga st  r dictors 
previously valida d. Th   full  inclusion and exclusi n criteria ar   listed  in Table 1. We 
lso considered  it rature w ich report d on the p rs ectives of a variety of key stake
hold rs; thi  all w  us  o  ain a comprehens ve and mul disciplinary assessment of bar
rie s a d facil tators throug out all st ges of implem ntation. Any  mple entation stu ‐
ies or other pri ary r se rch which fe u ed a qualitativ , quantitative  r mixed‐metho s 
examin tion of barri rs and/o   facil tators  re considere   for  inclusion. Given  the ex‐
treme pa city of actual implem ntation stu ies,6 we also considered studi s fo i clusi n 
w i  ad pt d a more hypothetic l  consideration of imple entation  ( .e., primary  re‐
search which involved s akeholder c nsultat on on the pr posed applicati n of  spects of 
pre is on psych atry methods). 
Table 1. Inclusion and exclusion criteria. 
  In lusion C iteria Exclusion Crite ia 
(I) Consultation 
with  key 
stakeholders 
Health and  ocial c e prof ssionals 
 Service  sers and family members and/or caregivers 
 Poli ymakers 
Research scie tists 
ocal co munity members 
NA 
I) Pre is on 
psychiat y 
approach 
Di s ic, predictive or prognost c models employ‐
ing   precision (or stratified) approach   
Specific to the field of psychiatry (i.e., any DSM/ICD 
di gnosis) 
 Precision m dels  relating  to 
traumatic brain  injury, neuro‐
l gical disorders or dementias 
(III) Pre ictors 
 Clini al 
 Soci d ogr phic 
ervi e use 
Behaviour l 
 Bi arkers  ( uroim ging,  genomic,  phar‐
macogeno ic, m tabol mic, cognitive) 
ny combination of the above 
NA 
IV) Study design 
P imary  r search  stud s which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Se ondary  research  (system
atic  nd  n n‐systemat c  re‐
v ews,  nd me a‐a alyses) a 
) Assessme t
of  bar iers/ 
facilitators 
 Systematic asse sment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers a d/or
f cilitat rs only  raised  in  the 
discussion section 
( I) Publication 
typ  
 Conference abstracts b 
 Full journal articles 
 Protocols 
d torials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level and 
quality of ev‐
idence 
  level or quality of evidence   
(VIII) Language   Any language  NA 
Systema ic asse sment of barriers and/or
facilitators o precision (or stratified) psych atry
Brai  Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The revi w pr t col (PROSPERO: CRD42020182595) aimed to identify releva t liter‐
ure  ich r p rte   sses ent of the factors  ffecting the real‐world i plementation 
 precisi n psychiatr   t o s, def ned as the application of any meth d encompassi g 
i gn stic, p ognostic, or pred ctiv model to estimate risk or outcomes at an individual‐ 
(precisi ) or subgroup‐l vel (str ti i d) [2]. There were no r strictions in place reg rding 
the  type   f p edictors  in use, and  th final  literature was clustered agai st predictors 
r vio sly valid ted. The  full clusion and exclusion criteria are  listed  in Table 1. We 
ls  c si er d  l t ratur  which report d on the perspectives of a variety of key stake‐
hold rs; this allowed us to g in a comprehensive and multidisciplinary assessment of bar‐
riers and facili ators throughout all stage   f implementation. Any implementation stud‐
ies or other primary  esearch wh ch featured a qualitative, quantitative or mixed‐methods 
examination of barri s and/or  facilitators were considered  for  inclusion. Given  the ex‐
tr me paucity of actual i plem ntatio  studies,6 we also considered studies for inclusion 
which ad pted a  ore hypo h tical  consid ration of  implementation  (i.e., primary  re‐
search w ich inv lve   takeholde  consul ation on the proposed application of aspects of 
precision psychiatry methods). 
Tabl  1. Inclusion and exclusi n crite ia. 
  Inclusion Cr teria  Exclu ion Criteria 
(I) Consultation 
with  key 
stake olde s 
 Health and social c re professio als 
 Servi e users and family me bers an /or caregivers 
 P licymakers 
 Research scientists 
 Local community me bers 
NA 
(II) Precision 
psychiatry 
approach 
 iagnostic, predic ve or prognostic models employ‐
i g a precision ( r stratifie ) approach   
 Specific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
 Sociodemographic 
 Service u e 
 B havi ural 
 Biomarkers  (neuroim ging,  genomic, phar‐
macogenomic, metabolo ic, cognitive) 
Any combination of the bove 
NA 
(IV) Study design 
Prim ry  esearch  tudies which  con i er  actual  or 
proposed implementati n 
 Qualitative, quantita ve  r mixed meth ds   
 Secondary  research  (system‐
atic  and  n ‐syst matic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
acilitators 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified)  sychiatry 
 Assessme t of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Lev l  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Assessment of barriers and/or fac litators
only raised in the discussion ction
(VI) Publication type
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30 
The review protocol (PROSPERO: CRD42020182595) aime  to identify relevant lit
ature which reported  n assessment of the factors affecting the real‐world  mple e tat
of precision psychiatry met ds, de ined as the application of any m thod encompassing
di gnostic, pr gnostic, or predic ive models t  estimate  isk  r ou comes at an indivi ual
(precision) or subgroup‐level (stratif ed) [2]. There were no restrictions in place regard g
the  type  of predict s  in use, and  the  final  literature was clustered against predict rs 
previously valid ted. The  full  inclusion and exclusion crite ia ar   listed  i Table 1. We
also considered  literature which reported on the perspectives of a variety of key stake‐
holder ; this allowed us to gain a comprehensive and multidis iplinary assessment of bar‐
riers and facilitators throughout all stages of i pleme ation. Any im lem nt tion stud‐
ies or other prim ry research which featured a qualitative, quantitative or mix d‐methods 
examination of barriers and/or  facilitators w re considered  for  inclusion. Given  the ex‐
tre e paucity of actual i plementation studies,6 we also considered studies for incl sion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search w i h inv lved stakeholder consultation on the proposed application of aspects of 
pre isi n psychiatry methods). 
T ble 1. Inclu on and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
s akeholders 
 Health and social car p ofessionals
rv ce user  and family memb r   nd/or  aregivers 
l cymakers 
 Research scientists 
Lo al community memb rs 
NA 
( ) cision 
psychi try 
appro ch 
Di s ic, predictive or pro nost c models em loy‐
ing a precision (or stratified) approach   
Specific t  the field o  psychiatry (i.e., any DSM/ICD 
diagn sis) 
 Pr ci io   dels  relating  to 
tra matic brain injury, neuro‐
logical disorders or deme tias 
II ) Predicto s 
li ical 
Sociodemographic 
Service us  
Behavioural 
 Bi markers  ( euroim ging,  genomic,  pha ‐
macogen mic, metabolomic, cognitive) 
  combination of the above 
NA 
IV  Study design 
Primary  r search  studi s which  consider  actual  or 
prop s d implementation 
 Qualitativ , quantitative or mix d methods   
 Secondary  research  (system‐
atic  nd  on‐ ystematic  re
views, and meta‐ nalyses) a 
) Assessme t 
of  barriers/ 
facili at rs 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psy hiatry 
Ass sment  f b rriers and/or 
f c litators  only  raised  in  the 
discussion section 
( I) P blication 
type 
Conference abstracts b 
Full journal artic es 
 Protocols 
ditorials, letters and commen‐
taries 
 Expert opinion papers c 
( II) evel  and 
quality of  v‐
idence 
evel or quality of evidence 
(VIII) Language   Any language  NA 
C fer nc a stracts b
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30 
The review p otocol (PROSPERO: CRD42020182595) aime   o id ntify relevant lite
ature which reporte  an asse sment of the f ctors affecting the real‐world implem tation 
of pr cision psychiatry m t ods, de ined   the ap lication  f  ny me hod encompas ing
di gn stic, pr gnostic, or predic ive models to e timate risk o  outco es at an individual  
(pre isio ) or subgro p‐lev l (stratif ed) [2]. Th re were n  re trictions in place regard ng
th   type  of predict s  in us , and  th   final  literature was clustere  against predictors 
previously valid ted. Th   full  in lusion and exclu ion criteria are  listed  i Table 1. We
als  considered  lit rature which  ep rted on the persp ctives of a variety of key stake‐
hold r ; t is  llowed us to gain   comprehensive a d  ulti i ciplinary ass sment of bar‐
i    f cilit rs throughout all stages of i plementatio . A y impl m nt tion stud‐
i s  r other primary research which feat red a q alitative, quantit tive or mixed‐ ethods 
xamination  f barriers an /or  facilita ors were considered  fo   inclusion. Given  the ex‐
tre e pa city of actual i plementation studies,6 we  lso  onside d  tudies for incl sion 
which adopted a more hypothetic l  consideration of  implementatio   (i.e., primary  re‐
search which involved stakehold  consultation on the proposed applicati n of  spects of 
pre is on psych atry methods). 
Table 1. Inclus on and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
s ake lders 
 Health and social care professionals 
 ic   rs and family  embers and/or  aregivers 
l cymakers 
 Research scientists 
Local co munity members 
A 
) cision 
psychiatry 
approach 
Diagn s , predictive or pro nostic models em l y‐
ing a precision (o  s ratified) approach   
 Specific to the field of psychiatry (i.e., any DSM/ICD 
d agnosis) 
 Pr ci io   odels  relating  to 
traumatic brain  injury, neuro‐
logical disorders or deme tias 
II red to s 
li ical 
Sociod mographic 
ervice us  
Behavioural 
 Biomarkers  (neuroimaging,  genomic,  pha ‐
macogen mic, m tabolomic, cognitive) 
 ny combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  co sider  actu l  or 
prop sed implementation 
 Qualitative, quantitat ve or mixed methods   
 Secondary  research  (system‐
atic  and  non‐ ystematic  re‐
views, and met ‐ nalyses) a 
( ) Assessment 
of  barriers/ 
facilitators 
Systematic assessment of barriers and/or facilitators 
to pr cision (or stratified) psy hiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Full journal articles
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protocol (PROSPERO: CRD42020182595) aimed to identify rel vant liter‐
tur   hi h rep rte   n ass s  of the factors affecting the real‐world implementati n 
of precision  sychiatr   t s, d fined   th  appl cation of  ny method encompassi  
diagn stic, p ognostic, o  predictiv  mo ls to estimat  risk or outcomes a  an individual‐ 
(pr cision) or subgroup‐l vel (str tifi d) [2]. Th re were no restrictions in place regarding 
the  types of predictors  in us , and th   final literature was clustered against predic ors 
pre i sly v li t . The  full  i lusion and exclusion criteria are  listed  in Table 1. We 
also consider d  lite ature which repor d on the persp ctives of a vari ty of key stake‐
hold rs; this allowed us to g in a compr h nsive  nd multidisciplinary ass sment of bar‐
riers a d facilitators through ut  ll st ge  of implementation. A y implementation stud‐
ies or other pr mary r s arch which feature  a quali ative, quantit tive or mixed‐methods 
examin ti n of ba riers and/or facilitators were considered  for  inclusion. Given  the ex‐
treme paucity  f a tual i plem tation studies,6 we also considered studies f r inclusion 
which ad pted    ore  ypoth tic l  consid ration of  implementation  (i.e., primary  re‐
search w ich inv lve  stakehold r consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stake olders 
H alth and soc al care professionals 
 S rvice users and family members and/or caregivers 
 P licymakers 
 Research scientists 
 Local community me bers 
 
(II) Precision 
psychiatry 
appr ch 
 iagnostic, predictive or prognostic model   ploy‐
ing a precision (or stratified) approach   
 Specific to the field of p y hiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
ociodemographic 
 Service use 
 Behavioural 
 Biomarkers  ( euroimag g,  genomic,  phar‐
macogenomic, metab lomic, cognitive) 
 Any combination of  he  bov  
NA 
(IV) Study design 
 Prim ry  search  studi s whi h  co i r  ctu l  or 
proposed implementation 
 Qualitative, quan itative  r mixed m thods  
 Second ry  r search  (system‐
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
 Systemati  assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 ditorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Lev l  and 
quality of  v‐
idence 
evel or quality of evidence 
(VIII) Language   Any language  NA 
Protocols
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30 
The review p otocol (PROSPERO: CRD42020182595) aime  to identify relevant liter‐
ature which rep rted  n as ess  of the factors affecting the real‐w rld implementation 
f precision psychiatr t s, d fi ed as the application  f any method encom assing 
diagnostic, p ognostic, or predictive mod ls to estimate risk or outcomes at an individual‐ 
(precision) or subgroup‐leve  (str tifi d) [2]. There were no restrictions in place regarding 
the types of pre ictors  in use, and  th   final  literature was clustered against predictors 
pr vi sly validate . The  f ll  i clusion and exclusion criteria are  listed  in Table 1. We 
also c sidered  literat re which  eported on the perspectives of a variety of key stake‐
hold rs; t is allowed us to g in a c mprehensive and multidisciplinary assessment of bar‐
iers a d facilitat rs throughout all stag  of implementation. Any implementation stud‐
ies  r other p imary research which featured a qualitative, quantitative or mixed‐methods 
examinat on of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual i plem ntation studies,6 we also considered studies for inclusion 
which ad pted a  re hyp th tical  consid ration of  implementation  (i.e., primary  re‐
search w ich inv lve  stakehold r consultation on the proposed application of aspects of 
precision psychi try methods). 
Table 1. Inclusion and ex lusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
w th  key 
stakeholders 
 Healt   nd social care professionals 
 Service users and f mily me bers and/or caregivers 
 Policymakers 
 R search scien sts 
 Local com unity members 
NA 
(II) Precision 
psychiatry 
appr ch 
 Diagnostic, predictive or pr gnostic models employ‐
ing a precision (or  ratified) approach   
 Specific to the field of p ychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
 Soci d mographic 
 Servi e use 
 Behavioural 
 Biomarkers  (neuroim g g,  genomic,  phar‐
macogenomic, metab lo ic, cognitiv ) 
 Any combination of  he bove 
NA 
(IV) Study design 
 Primary  esearch  studies which  consider  actual  or 
proposed implementation 
 Qualitative, quantitat ve or mixed m thods  
 Secondary  research  (system‐
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
( ) Assessment 
of  barriers/ 
facilitators 
 Systematic assessmen f barriers and/or facilitators 
to precision (or stratified) psych atry 
 Assessment of barriers and/or 
f cilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence NA 
(VIII) Language   Any language  NA 
Edit rials, letters and commentar es
Brain Sci. 2022, 12, x FOR PEER REVIEW 3 of  30 
The review protocol (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which rep rted an assess  of the factors affecting the real‐world implementation 
of precision  sychiatry methods, d fined a  the application of any method encompassing 
d agnostic, prognostic, or predictive mod ls to estimate risk or outcomes at an individual‐ 
(precision) or subgroup‐level (stratified) [2]. There were no restrictions in place regarding 
the  types of predictors  in use, and  the  final  literature was clustered against predictors 
previ usly validated. The  full  i clusion and exclusion criteria are  listed  in T ble 1. We 
lso co idered  literature which reported on the perspectives of a variety of key stake‐
holders; this allowed us to gain   compreh nsive and multidisciplinary assessment of bar‐
riers  nd facilitators throughout all stag s of implementation. Any implementation stud‐
i s   oth r primary research which featured a qualitative, quantitative or mixed‐methods 
examination of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity  f a tual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakehold r consultation on the proposed application of asp cts of 
precision psychiatry methods). 
Table 1. Inclusion and ex lusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakehold s 
Healt   nd social care professionals 
 Service users and family members and/or caregivers 
 Policymakers 
 Research scie tists 
 Local community members 
NA 
(II) Precision 
psychiatry 
appr ch 
 Di stic, predictive or prog ostic mo els employ‐
ing a precision (or stratif ed)  pproach   
 Specific to the field  f psychiatry (i.e., any DSM/ICD 
diagnosis) 
Precision  mod ls  relating  to 
traumatic brain  injury, neu o
logical disorders or dementias 
(III) Predictors 
Clinical 
ociodemographic 
S rvice  se 
ehaviou al 
 Bio arkers  (neuroim ging,  genomic, phar‐
macogeno ic, metab lomic, cognitive) 
Any combinatio of  he bov  
NA 
(IV) Study design 
 Primary  research  studies which  con i er  actual  or 
proposed implementati n 
 Qualitative, quan itative  r mixed m th ds   
Secondary  research  (system‐
atic  nd  non‐systemat c  re‐
v ews, and me a‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
 Systematic assessmen  of barriers and/or facilitators 
to precision (or stratified) psych atry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
) Publication 
type 
Conference  bstracts b 
 Full journal articles 
Pro cols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Lev l  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Expert opinion papers c
(VII) Level and quality of evidence
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The rev ew pr tocol (PROSPERO: CRD42020182595) aim  to de tify releva t liter
ture w ich repo ted an  sessment  f the f cto s  ffecting the real‐world i plemen tio
of precision psychiatry methods, def ned as th  applicati n o  any meth d enco passing
diagnostic, prognostic, or p dictive models to est mate  isk or  tcom s at an  ndividual‐
(pre ision) or subgroup‐level (stratified) [2]. There were no r s ric ions in place reg ding 
the  types of predictors  in use,    the  final  literature was cluste ed agai st predictors
viously valid ted. The  full  inclusion and exclu n criteria are  listed  in Table 1. We 
als  considered  literatu e which reported on the perspective   f a vari ty of key stake‐
hold r ; this  llowe  us to gain a  omprehensive and mul idisciplinary assessment of bar‐
riers and f cilit tors throughout all stages of implementation. Any i pl mentatio  stud‐
es or other primary research whi featured   quali ative, q antitative or mixed‐m th ds 
xaminatio  of barriers and/or  facilitators wer  considered  for  inclusion. Given  the ex‐
tre e pa city of actual implementation studies,6 we also considered studies for inclusion 
whic  adopted a more hy othetical  consideration of  implem ntation  (i.e., primary  re‐
search w i h inv lved st keholder consultation on the proposed applic tion of  spects of 
precision psychiatry methods).
Table 1. In lusion and exclusi n criteria. 
  I cl sion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
Health and social c r   ofess nals
rs a d family members  nd/or care ivers 
 Policymakers 
Rese ch sci ntists 
Loc l c m unity  embers 
 
(II) Prec sion 
psychiatry 
approach 
 Diagno ic, predictive or prognos c models employ‐
ing a pr cis on (or stratified) appro ch   
 Specific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Pr ci io   odels relating  to 
raumatic brain  injury, neuro
logical disorder  or dementias 
(III) Predict rs 
 Clinical 
 Sociodemographic 
 Service use 
 Behavioural 
Bi markers  ( eur im ging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
 ny combination of the  bove 
NA 
IV) Study design 
Primary  research  studi s which  consider  actual  or 
proposed implementation 
Qualitative, quantitativ  or mix d methods   
Secondary resea ch  (system‐
atic  and  no ‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessme t 
of  barriers/ 
facilitators 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
As sment  f b rriers and/or 
f cilitators  only  raised  in  the 
discussion section 
( I) P blication 
type 
Conference abstracts b 
Full journal articles 
 Protocols 
ditorials, lett rs and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of  v‐
idence 
evel or quality of evidence 
(VIII) Language   Any language  NA 
ny lev l or quality of evidence
NA
(VIII) Language
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The revi w protocol (PROSPERO: CRD42020182595) aime   o  d ntify releva t liter‐
ature which r ported an ssessment  f the factors affe ting the r al‐w ld  pl entat on
of pr cis on psych atry methods, d f e  a he application  f any me hod e com as ng
diagnostic, prognostic, or p edictive models to estimate risk or outc me  at   individual
(pr i ion) or subgroup‐lev l ( tratified) [2]. There were n  re trictions in place regarding
th   typ s of predictors  in use,   the  final literatur  was clus e d aga st pr dict rs
previously valida d. Th   full  nclusion and  xclusio  crit r a are  list d  in T ble 1. We 
lso con idered  lit rature which report d on the perspective of a v riety of key stake
hold rs; this allowe  us t   ain   compreh n ve and mul d sciplin y assessmen  of bar
riers  nd facil ta ors throug out all st ges of i pleme ation. Any  ple entation stu ‐
i s or oth r primary r se rch which fe u ed a qualitat v , quantitative o  mixed‐ e hods 
exa in tion of b rri rs and/or  facil tators w re consid red for  inclusi n. Given  the ex‐
treme paucity of actual implem ntation stu ies,6 we also considered studi s fo i clusion 
w i  ad t d a  ore hyp thetic l  consideration of implementati n  ( .e., primary  re‐
search whi h involved s akeholder c nsult t on on the proposed appl cation of asp cts of 
precis on psych atry methods).
Table 1. Inclusion and exclusion crit ria. 
  In lusion C ite ia Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
Health  nd ocial c   of ssionals 
Service users and family me ber nd/or caregivers 
olicymakers 
R e ch sc ti ts 
 Loc l  om u ity member  
 
(II) Pre is on 
psychiat y 
approach 
 Di sti , predictive or prognostic models empl y‐
ing a precision (o   rat fied) approach   
 Specific to the f eld of psychiatry (i.e., any DSM/ICD 
diagnosis) 
Prec sion  od ls  relating  to 
traumatic brain  injury, neu o
logical disorders or dementias 
(III) Predictors 
li ical 
 ociodemographic 
ervice use 
Behavi ur l 
 Biomarkers  (n uroimaging,  genomic,  phar‐
macogenomic, metabol mic, cognitive) 
 Any combination of the above 
 
(IV) Study design 
 P imary  research  stud es which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mix d methods   
 Se ondary research  (system
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
( ) Assessment 
of  bar iers/ 
facilitators 
 Systematic asse sment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
Ass sment of barriers a d/or
facilitators only  raised  in  the 
discussion section 
) Publication 
type 
 Conference abstracts b 
Full journal artic es 
 Protocols 
 Ed torials, letters and commen‐
taries 
 Expert opinion papers c 
) evel and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Any lan uage
NA
(IX) Publication date
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The revi w pro ocol (PROSPERO: CRD42020182595) aimed to ide tify releva  lit r
atu e wh h reported  n ass ssment  f the f ctor  affe ting the real‐w rld  mple entat
of prec s  p ych at y meth ds, d fine  a   he a plication  f any method e compass
d gnostic, prognos ic, or pr dictive models t  estimat risk  r outc mes at an individual‐
(pr ci io ) or subgroup‐l vel ( tratified) [2]. There were no restriction  i  plac  regarding
th   typ  of predict rs  in use, and  the  final iterature was clustered  ga st pr dictors
previously va ida d. Th full  in lusion and exclusion cr teria are  listed  in Table 1. We 
als considered  lit rature which  eport d on t e p s ective   f a vari ty of key st ke
hold rs; this allowe  us to  ain a  ompreh ns ve  nd mul disciplin ry assessment  f bar
rie s a d facil tat s throug ut  ll s ges of i plementation. Any  ple entatio  stu
ies or other pri ary r se rch which fe u e  a qualitativ , quantitativ  or mixed‐methods
examin ti n of b rriers and/or  fa il tator  w re considered  for  inclusion. Give   the ex
treme paucity of actual implem ntation stu s,6 we also consider d stud s f inclusi n
w i  ad pted   more  y othetical  consideration  f imple entation  ( .e., primary  re‐
search which involved s akeholder c nsultat on on the pr posed applic ti n of  spects of 
pre ision psychiatry  ethods). 
Table 1. Inclusion and exclusion crit ria. 
  I lusion Criteria Exclusio  Criteria 
( ) Consultation 
with  key 
stakeholders 
He lth and  ocial c e pr f ssionals 
S rvice us rs  nd family members a d/or caregivers 
licymaker  
Research scie ti ts 
 Local c mmunity members 
NA 
) is on 
psychiat y 
approach 
Diagn stic, predictive or prognostic models  mp y‐
ing a precision (or str tified) approach   
pecific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  m dels  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
II red tors 
 li ical 
 Sociod mographic 
Service use 
Beh vioural 
Bio rkers  (n uroimaging,  genomic,  pha ‐
macogen ic, m tabol mic, cognitive) 
  combinatio  of the above 
(IV) Study design 
 P imary  research  stud es which  consider  actual  or 
proposed implementation 
Qualitative, quantitative or mixed methods   
 Se ond ry  r search  (system
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
) Assessment
of  b r iers/ 
facilitators 
 Systematic asse sment of barriers and/or facilitators 
to precision (or stratified) psy hiatry 
 A essment of barriers a d/or
facilitators only  raised  in  the 
discussion section 
( I) P blication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Ed torials, lett rs and commen‐
taries 
 Expert opinion papers c 
(VII) Lev l and 
quality of  v‐
idence 
  level or quality of evidence   
(VIII) Language   Any language  NA 
ublished from dat base inc ption to
25 October 2020 NA
a R views were screen d for relevant research via the hand-searching of bibliographies. b Conference ab t acts
were only included if they fit all other criteria, including the reporting of primary research data. c Expert opinion
papers were flagged for inclusion should the fina literature base be too narrow to facilitate sufficient discussion
(<5 studies). DSM = Diagnostic Statistical Manual (any version); ICD = Int rnational Cla ifi a i n of Diseases
(any version).
Database results were exported into EndNote X9 and screened within the application.
The lead reviewer (HB) conduct d title and abstract scree ing on all exported records in
line with the inclusion crite ia outlined below. A second reviewer independently screened
a random 50% sampl of the records ( LD) du to the exte siv number of initial database
results. All abstracts which appeared to meet the inclusion criteria were carried forward to
full-text screeni g; the ntire full-text screening process was conducted by two in epen-
dent researchers (HB, LLD). Any uncertainties over screening or full-tex decisions were
consulted with the wider review team and eventually with a senior researcher (PFP).
2.2. Level of Evidence
Given the expected narrow final literature base and in the interest of inclusivity, we
made the decision not to exclude based upon level or quality of evidence. Instead, we
adhered to a simple numerical ranking system to indicate the level of evidence: 1 denotes
Brain Sci. 2022, 12, 934 4 of 25
stakeholder consultation, 2 denotes pilot and feasibility studies, and randomized controlled
trials (RCT) will be assigned a score of 3 to denote higher grade evidence.
2.3. Data Extraction and Analysis
A fit-for-purpose data extraction form was designed for this review and was first
trialed on five studies and subsequently adjusted as necessary before proceeding with the
remaining studies. Data extraction was independently conducted by two reviewers (HB,
LLD) to ensure all relevant information was captured. Supplementary Materials outline
the categories of data which were extracted for each record (Methods S2).
The identified barriers and facilitators were systematically synthesized, modelled
upon a systematic approach adopted in a recent review addressing the implementation
of digital health interventions for psychosis, and bipolar specifically [22]. As such, the
data synthesis was guided by the ‘Consolidated Framework for Implementation Research’
(CFIR) [23], which provides an outline of factors commonly associated with the implemen-
tation of innovation into clinical practice, corresponding to five key constructs: intervention
characteristics, outer setting, inner setting, characteristics of the individuals and the im-
plementation process (described below). Here, we made two minor revisions to these
constructs. First, as many precision psychiatry models are not necessarily intervention-
based, the ‘Intervention characteristics’ construct is hereafter referred to as ‘Characteristics
of the model’. Second, the ‘Characteristics of the individuals’ construct will be divided into
separate ‘Staff’ and ‘Service user’ constructs in recognition of their distinct roles in the im-
plementation process. Sub-factors were then grouped and discussed within each construct
post-hoc based upon thematic or conceptual similarities raised within the literature.
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protocol (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which reported an assessment of the factors affecting the real‐world implementation 
of precision psychiatry methods, defined as the application of any method encompassing 
diagnostic, prognostic, or predictive models to estimate risk or outcomes at an individual‐ 
(precision) or subgroup‐level (stratified) [2]. There were no restrictions in place regarding 
the  types of predictors  in use, and  the  final  literature was clustered against predictors 
previously validated. The  full  inclusion and exclusion criteria are  listed  in Table 1. We 
also considered  literature which reported on the perspectives of a variety of key stake‐
holders; this allowed us to gain a comprehensive and multidisciplinary assessment of bar‐
riers and facilitators throughout all stages of implementation. Any implementation stud‐
ies or other primary research which featured a qualitative, quantitative or mixed‐methods 
examination of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusio  Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social care professionals 
 Service users and family members and/or caregivers 
 Policymakers 
 Research scientists 
 Local community members 
NA 
(II) Precision 
psychiatry 
approach 
 Diagnostic, predictive or prognostic models employ‐
ing a precision (or stratified) approach   
 Specific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
 Sociodemographic 
 Service use 
 Behavioural 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
 Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Char cteri tics of the model: This construct addresses logistical and practical features
of the m del which may impact upon implementation, as well as more conceptual
components of the model and the corresponding strength, accuracy and transparency
of the evidence upon which the model is based.
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protocol (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which reported an asse sment of the f ctors affecting the real‐world implem nta ion 
of precision psychiatry m thods, defined  s the application of  ny method encompassing 
diagn stic, prognostic, or predictive models to estimate risk or outcomes at an individual  
(precision) or subgro p‐level (stratified) [2]. Th re were no restrictions in place regarding 
the  types of predictors  in use, and  the  final  literature was clustered agains  predictors 
previously valid ted. The  full  in lusion and exclusion criteria are  listed  in Table 1. We 
also considered  literature which repor ed on the persp ctives of a variety of key stake
hold rs; this allowed us to gain a comprehensive and multidi ciplinary ass sment of bar‐
riers and facilitators throughout all stages of implementation. A y implementation stud
i s or other primary research which feat red a quali ative, quantit tive or mixed‐methods 
examination of ba riers an /or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetic l  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusi  Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social care professionals 
 Service users and family members and/or caregivers 
 Policymakers 
 Research scientists 
 Local community members 
NA 
(II) Precision 
psychiatry 
approach 
 Diagnostic, predictive or prognostic models employ‐
ing a precisi  (or stratified) approach   
 Sp cific to the field of psychiatry (i.e., any DSM/ICD 
diagn sis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
 Sociodemographic 
 Service use 
 Behavioural 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
 Any combination of the above 
NA 
(IV) Study design 
 Primary  research  studies which  co sider  actu l  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/ 
facilitators 
Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Inner setting: Whilst the inner and outer setting constructs are closely linked and are
consid red inter-dependent in many respects, this construct refers largely to features
of local nfrastructure within which the model will be implemented.
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protoc l (PROSPERO: CRD42020182595) aimed to identif  relevant liter‐
ature which  eporte  an ass ssment of the factors affecting the real‐world impl mentat on
of precision psychiatry met ods, defin d as the application of any method e compassing
diagnostic, rognostic, or predictive models to estimate risk or outcomes at an individual‐
(precision) o  subgroup‐l vel (stratified) [2]. There were no restrictions in place r garding 
the  ty es of predictor   in use, and  the  final  literature was clustered  gain t predicto s 
previously validated. The  full  inclusion and exc usio  cr teria are  listed  in T ble 1. We 
al o c nsidered  literature w ich reported on the pers ctives of a  ariety of key stake‐
holders;  his allowed u  to gain a comprehensiv and multi isciplinary assessm t of bar
ri rs and facilitators throughout all stages of implementatio . Any implementat on stud‐
ies or other prim ry research which feature  a qualitative, quantitative or mixed‐ ethods 
ex mination of barrier   nd/ r  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakehold  consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  I clusion Criteria  Exclusio  Criteria 
(I) Consultation 
with  key 
stakeh lders 
Health and social care professionals 
ervice users and family members and/or caregivers 
 Policymakers 
 Research scientists 
 Local community members 
NA 
(II) Precision 
psychiatry 
approach 
 Diagnostic, predictive or prognostic models employ‐
ing a precision (or stratified) approach   
 Specific to the field of psychiatry (i.e., any DSM/ICD 
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or dementias 
(III) Predictors 
 Clinical 
 Sociodemographic 
 Service use 
 Behavioural 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
 Any combination of the above 
NA 
IV Study design 
 Primary  research  studies which  consider  actual  or 
propos d impl menta i n 
Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  non‐ ystematic  re
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/
faci at rs 
 Systematic assessment of barriers and/or facilitators 
to pr cision (or stratified) psychiatry 
 Ass ssment  f b rriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Outer setting: Closely intertwined with the inner setting, the outer setting largely takes
into consideration the wider system and the external organizations who exist outside
of the inner setting, and as such this construct typically addresses the economic, social,
cultur l and politic l contexts within which the model is being implemented.
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protocol (PROSPERO: CRD42020182595) aimed to identif  relevant liter‐
ature which reporte  an asse sment of the f ctors affecting the real‐world implem nta ion 
of precision psychiatry m t ods, defined  s the application of  ny method e compassing 
diagnostic,  rognostic, or predictive models to estimate risk or outcomes at an individual  
(precision) or subgro p‐level (stratified) [2]. There were no restrictions in place regarding 
the  ty es of predictors  in use, and  the  final  literature was clustered agains  predictors 
previously valid ted. The  full  in lusion and exclusion criteria are  listed  in Table 1. We 
also considered  literature w ich repor ed on the pers ctives of a variety of key stake
hold rs; this allowed us to gain a comprehensive and multidi ciplinary ass sment of bar‐
riers and facilitators throughout all stages of implementation. A y implementation stud
i s or other prim ry research which feat red a quali ative, quantit tive or mixed‐methods 
examination of ba riers an /or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for inclusion 
which adopted a more hypothetic l  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. Inclusion and exclusion criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social care professionals 
 ervice users and family members and/or caregivers 
 Policymakers 
R search scientists 
 Local  ommunity m bers 
NA 
(II) Precision 
psychiatry 
approach 
 Diagnostic, predictive or prognostic models employ‐
ing a precision (or stratified) approach   
Specific to the field of psychiatry (i.e., any DSM/ICD
diagnosis) 
 Precisio   models  relating  to 
traumatic brain  injury, neuro‐
logical disord rs or dementias 
(III) Predictors 
 Clini  
 Sociodemographic 
 Service use 
 Behavioural 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, metabolomic, cognitive) 
 Any combination of the above 
NA 
IV Study design 
 Primary  research  studies which  co sider  actu l  or 
propos d implementation 
Qualitative, quantitative or mixed methods   
 Secondary  research  (system‐
atic  and  non‐ ystematic  re
views, and meta‐analyses) a 
(V) Assessment 
of  barriers/
faci at rs 
Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Ass ssment  f b rriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Char cteri tics of the individuals: This construct considers the individuals involved in
the imple entation process at the ground-level, including both those involved in the
de ivery of clin al care and those in receipt of this care. As such, in this current study,
we divided this construct into two independent groups of stakeholders due to their
unique needs and perspectives: (i) health and social care staff involved in the delivery
of care and (ii) service users and their families/caregivers. These constructs address
the at itudes, opin ons, previous exp riences, skills/knowledge, concerns, needs and
potential impact of precision psychiatry models on these key stakeholder grou s.
Brain Sci. 2022, 12, x FOR PEER REVIEW  3  of  30  
The review protocol (PROSPERO: CRD42020182595) aimed to identify relevant liter‐
ature which reported an assessment of the factors affecting the real‐world implementation 
of precision psychiatry methods, defined as the application of any method encompassing 
diagnostic, prognostic, or predictive models to estimate risk or outcomes at an individual‐ 
(precision) or subgroup‐level (stratified) [2]. There were no restrictions in place regarding 
the  types of predictors  in use, and  the  final  literature was clustered against predictors 
previously validated. The  full  inclusion and exclusion criteria are  listed  in Table 1. We 
also considered  literature which reported on the perspective   f a vari ty of key stake‐
holders; this allowed us to gain a comprehensive and mul idisciplinary assessment of bar‐
riers and facilitators throughout all stages of implementation. Any implementatio  stud‐
ies or other primary research which featured a qualitative, quantitative or mixed‐methods 
examination of barriers and/or  facilitators were considered  for  inclusion. Given  the ex‐
treme paucity of actual implementation studies,6 we also considered studies for incl sion 
which adopted a more hypothetical  consideration of  implementation  (i.e., primary  re‐
search which involved stakeholder consultation on the proposed application of aspects of 
precision psychiatry methods). 
Table 1. In lusion and exclusi n criteria. 
  Inclusion Criteria  Exclusion Criteria 
(I) Consultation 
with  key 
stakeholders 
 Health and social care  rofessionals 
 Service users and family members and/or caregivers 
Policymakers 
 Research scientists 
 Local com unity  embers 
NA 
(II) Precision 
psychiatry 
approach 
 Diagn stic, predictive or prognostic models employ‐
ing a precision (or stratified) approach   
pecific  o the field of psychiatry (i.e., any DSM/ICD
diagnosis) 
 Precision  models  relating  to 
traumatic brain  injury, neuro‐
logical disorders or deme tias 
(III) Predictors 
 Clinical 
 Sociodemographic 
 Service use 
 Behavioural 
 Biomarkers  (neuroimaging,  genomic,  phar‐
macogenomic, m tabolomic, cognitive) 
 Any combination of the above 
NA 
(IV) Study design 
Prima y  r search  studies which  consider  actual  or 
proposed implementation 
 Qualitative, quantitative or mixed methods   
Second ry  research  (system
atic  and  non‐systematic  re‐
views, and meta‐analyses) a 
) Assessment 
of  barriers/ 
facilitators 
 Systematic assessment of barriers and/or facilitators 
to precision (or stratified) psychiatry 
 Assessment of barriers and/or 
facilitators  only  raised  in  the 
discussion section 
(VI) Publication 
type 
 Conference abstracts b 
 Full journal articles 
 Protocols 
 Editorials, letters and commen‐
taries 
 Expert opinion papers c 
(VII) Level  and 
quality of ev‐
idence 
 Any level or quality of evidence  NA 
(VIII) Language   Any language  NA 
Implem ntation process: Fi ally, this process const uct relates to factors which may
affect the actual procedure and operations of implementation, including uptake of
and adherence to the process.
3. Results
3.1. Literature Search
Following de-duplication, 93,886 records were screened by abstract, of wh ch 407 were
carried forward to full-text screening. A final 28 records met all inclusion criteria (Figure 1).
Brain Sci. 2022, 12, 934 5 of 25rain Sci. 202 , 12, x FOR PEER REVIEW 6 of 30 
 
 
Figure 1. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) diagram 
detailing the full study selection process. 
3.2. Description of the Included Studies 
The included records were published between 1996 and 2020. The final literature base 
represented global research from various sites; United States (n = 15; 53.6%), United King-
dom (n = 3; 10.7%), Australia (n = 3; 10.7%), Spain (n = 2; 7.1%), Canada (n = 1; 3.6%), New 
Zealand (n = 1; 3.6%), Singapore (n = 1; 3.6%), Demark (n = 1; 3.6%), and one study span-
ning 22 countries across North and South America, Europe, and Asia-Pacific regions. 
Just seven (25.0%) of the 28 included records reported barriers and facilitators de-
rived from the actual real-world implementation of precision psychiatry methods; two 
feasibility studies [24,25], one case example [26], and four qualitative studies employing 
surveys and/or interviews [27–30]. The remaining studies (n = 21; 75.0%) [31–51] were not 
primarily based on implementation data but rather based upon qualitative stakeholder 
consultation on the hypothetical implementation of precision psychiatry methodologies. 
There were no relevant RCTs identified during the screening process. 
A diverse range of stakeholders’ opinions were represented within the final literature 
base and several studies presented the perspectives of more than one type of stakeholder 
Figure 1. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) diagram
detailing the full study selection process.
3.2. Description of the Included Studies
The included records were published between 1996 and 2020. The final literature
base represented global research from various sites; United States (n = 15; 53.6%), United
Kingdom (n = 3; 10.7%), Australia (n = 3; 10.7%), Spain (n = 2; 7.1%), Canada (n = 1; 3.6%),
New Zealand (n = 1; 3.6%), Singapore (n = 1; 3.6%), Demark (n = 1; 3.6%), and one study
spanning 22 countries across North and South America, Europe, and Asia-Pacific regions.
Just seven (25.0%) of the 28 included records reported barriers and facilitators derived
from the actu l re l-world implementation of precision psychiatry methods; two feasibility
studies [24,25], one case x mple [26], and four q alitative studies employing surveys
and/or inte views [27–30]. The remaining studies (n = 21; 75.0%) [31–5 ] were not primarily
based on implementation data but rather based upon q alitative s keholder c nsultation
on the hyp thetical impl mentation of precision sych atry methodologies. There were no
r l vant RCTs identified duri g the screening proc ss.
A diverse range of stakeholders’ opinions w re repr sented within the fin l lit rature
base and s veral studies presented the rsp ctives f more than one type of stakeholder
group including (Figure 2): health care professionals, such as psychiatrists, psychologists,
nurses, medical students, and general physicians amongst other health professionals
Brain Sci. 2022, 12, 934 6 of 25
(n = 23; 82.1%) [24,25,27–30,32–46,50,51], service users (n= 9; 32.1%) [25,31,35,39,41,43,46–48],
caregivers or family members (n = 5; 17.9%) [24,35,39,43,47], community members (n = 3;
10.7%) [36,48,49], and research scientists (n = 2; 7.1%) [26,36]. There were no included
studies which consulted policymakers.
Brain Sci. 2022, 12, x FOR PEER REVIEW 7 of 30 
 
group including (Figure 2): health care professionals, such as psychiatrists, psychologists, 
nurses, medical students, and general physicians amongst other health professionals (n = 
23; 82.1%) [24,25,27–30,32–46,50,51], service users (n = 9; 32.1%) [25,31,35,39,41,43,46–48], 
caregivers or family members (n = 5; 17.9%) [24,35,39,43,47], community members (n = 3; 
10.7%) [36,48,49], and research scientists (n = 2; 7.1%) [26,36]. There were no included stud-
ies which consulted policymakers. 
 
Figure 2. The stakeholder groups investigated across the included literature and the proportion (%) 
of studies consulting each group. 
Further, the included literature represented a range of specialist fields of psychiatry 
(Figure 3); general psychiatry (n = 14; 50.0%) [27,28,30,33,34,36–40,42–45], major depres-
sion/mood disorders (n = 7; 25.0%) [29,31,35,41,48,49,51], bipolar disorder (n = 3; 10.7%) 
[46,47,51], suicidal behaviors (n = 2; 7.1%) [26,32], psychosis (n = 1; 3.6%) [51], child psy-
chiatry (n = 1; 3.6%) [24], alcohol use disorders (n = 1; 3.6%) [50], and the clinical high-risk 
for psychosis (CHR-P) state (n = 1; 3.6%) [25]. 
 
Figure 3. The fields of psychiatry investigated across the included literature and the proportion (%) 
of studies investigating each field. 
There was also a diverse range of precision approaches considered within the litera-
ture (Figure 4), including: genetic testing (n = 12; 42.9%) [35–37,40,42,43,45–47,49–51], 
pharmacogenomics (n = 7; 25.0%) [24,27,28,30,33,38,44], clinical prediction models and 
risk calculators (n = 6; 21.4%) [25,26,29,31,32,48], clinical decision supports (n = 2; 7.1%) 
[38,39], functional brain imaging (n = 1; 3.6%) [41], and general Artificial Intelligence (AI)/ 
Machine Learning (ML) applications (n = 1; 3.6%) [34]. This final literature base discussed 
a wealth of potential barriers and facilitators which covered the range of established CFIR 
0 10 20 30 40 50 60 70 80 90
Health care professionals
Service users
Family members/caregivers
Community members
Research scientists
Policymakers
Proportion of studies (%)
Stakeholder Groups
0 10 20 30 40 50 60
General psychiatry
Depression & mood disorders
Bipolar disorder
Suicidal behaviours
Psychosis
Child psychiatry
Alcohol use disorders
Clinical high risk for psychosis
Proportion of studies (%)
Field of Psychiatry
Figure 2. The stakeholder groups investigated across the included literature and the proportion (%)
of studies consulting each group.
Further, the included literature represented a range of specialist fields of psychia-
try (Figure 3); general psychiatry (n = 14; 50.0%) [27,28,30,33,34,36–40,42–45], major de-
pression/mood disorders (n = 7; 25.0%) [29,31,35,41,48,49,51], bipolar disorder (n = 3;
10.7%) [46,47,51], suicidal behaviors (n = 2; 7.1%) [26,32], psychosis (n = 1; 3.6%) [51], child
psychiatry (n = 1; 3.6%) [24], alcohol use disorders (n = 1; 3.6%) [50], and the clinical
high-risk for psychosis (CHR-P) state (n = 1; 3.6%) [25].
Brain Sci. 2022, 12, x FOR PEER REVIEW 7 of 30 
 
group including (Figure 2): health care professionals, such as psychiatrists, psychologists, 
nurses, medical students, and general physicians amongst other health professionals (n = 
23; 82.1%) [24,25,27–30,32–46,50,51], service users (n = 9; 32.1%) [25,31,35,39,41,43,46–48], 
caregivers or family members (n = 5; 17.9%) [24,35,39,43,47], community members (n = 3; 
10.7%) [36,48,49], and research scientists (n = 2; 7.1%) [26,36]. There were no included stud-
ies wh ch consulted policymakers. 
 
Figure 2. The stakeholder groups investigated across the included literature and the proportion (%) 
of st dies consulting each group. 
Further, the included literature represented a range of specialist fields of psychiatry 
(Figure 3); general psychiatry (n = 14; 50.0%) [27,28,30,33,34,36–40,42–45], maj r depres-
sion/mood disorders (n = 7; 25.0%) [29,31,35,41,48,49,51], bipolar disorder (n = 3; 10.7%) 
[46,47,51], suici al behaviors (n = 2; 7.1 ) [26,32], psychosis (n = 1; 3.6%) [51], child psy-
chiatry (n = 1; 3.6%) [24], alco ol use disorders (n = 1; .6%) [50], and the clinical high-risk 
for psychosis (CHR-P) state (n = 1; 3.6%) [25]. 
 
Figure 3. The fields of psychiatry investigated across the included literature and the proportion (%) 
of studies investigating each field. 
There was also a diverse range of precision approaches considered within the litera-
ture (Figure 4), including: genetic testing (n = 12; 42.9%) [35–37,40,42,43,45–47,49–51], 
pharmacogenomics (n = 7; 25.0%) [24,27,28,30,33,38,44], clinical prediction models and 
risk calculators (n = 6; 21.4%) [25,26,29,31,32,48], clinical decision supports (n = 2; 7.1%) 
[38,39], functional brain imaging (n = 1; 3.6%) [41], and general Artificial Intelligence (AI)/ 
Machine Learning (ML) applications (n = 1; 3.6%) [34]. This final literature base discussed 
a wealth of potential barriers and facilitators which covered the range of established CFIR 
0 10 20 30 40 50 60 70 80 90
Health care professionals
Service us rs
Family me bers/caregiv rs
Community members
Research scientists
Policymakers
Proportion of studies (%)
Stakeholder Groups
0 10 20 30 40 50 60
General psychiatry
Depression & mood disorders
Bipolar disorder
Suicidal behaviours
Psychosis
Child psychiatry
Alcohol use disorders
Clinical high risk for psychosis
Proportion of studies (%)
Field of Psychiatry
Figure 3. The fields of psychiatry investigated across the included literature and the proportion (%)
of studies investigating each field.
There was also a diverse range of precision approaches considered within the liter-
ature (Figure 4), including: ge etic testing (n = 12; 42.9%) [35–37,40,42,43,45–47,49–51],
pharmacogenomics (n = 7; 25.0%) [24,27,28,30,33,38,4 ], clinical prediction models and risk
calcul t rs ( = 6; 21.4%) [25,26,29,31,3 ,48], clinical decision suppo ts (n = 2; 7.1%) [38,39],
fun tional brain imaging (n = 1; 3.6%) [41], and ge er l Art ficial Intelligence (AI)/ Ma-
chine Learning (ML) applications (n = 1; 3.6%) [34]. This final literature base discussed
a wealth of potential barriers and facilitators which covered th range of established
CFIR constructs [23]. Table 2 offers a detailed breakdown of the characteristics of the
included studies.
Brain Sci. 2022, 12, 934 7 of 25
Table 2. Characteristics of the included studies.
First Author, Date Location Research Method Field of Psychiatry Type of PrecisionModel Sample Level of Evidence Summary of Barriers
Summary of
Facilitators
Bellón, 2014 [31] Spain Focus groups Depression Individualised riskprediction algorithm 52 service-users 1
Resistance to knowledge
of risk scores; Negative
attitudes towards
psychiatry
Adequate skills and
competence training;
Availability of effective
interventions and
counselling
Brown, 2020 [32] United States Survey Suicidal behaviours Individualised riskprediction algorithm
139 health care
professionals
(psychologists, social
workers, psychiatrists,
nurses and other allied
health professionals)
1
Poor accuracy and utility
of the model; Poor
transparency and
complexity of the model
N/A
Chan, 2017 [33] Singapore Survey General psychiatry Pharmaco-genomics
167 doctors and
27 pharmacists
(n = 194)
1
Poor perceived
competence in precision
medicine; Negative staff
perceptions of precision
medicine; Cost and time
investments; Lack of clear
guidelines; Potential
psychological harm;
Potential economic and
occupational harm
Availability of
associated
infrastructure
Doraiswamy, 2020 [34]
North America, South
America, Europe and
Asia-Pacific
Survey General psychiatry General AI/MLapplications 791 psychiatrists 1
Poor perceived relative
advantage of the model;
Negative staff perceptions
of precision medicine
N/A
Dunbar, 2012 [27] † New Zealand Surveys and interviews General psychiatry Pharmaco-genomics 33 senior medicalofficers and registrars 1
Lack of clinical resources;
Poor perceived
competence in precision
medicine; Poor perceived
relative advantage of the
model; Cost and time
investments; Potential
psychological harm
N/A
Erickson, 2013 [35] United States Survey Mood disorders Genetic testing
147 service users,
caregivers and
community members,
and mental health
professionals
1
Negative staff perceptions
of precision medicine;
Scepticism in genetics
Availability of
associated
infrastructure
Brain Sci. 2022, 12, 934 8 of 25
Table 2. Cont.
First Author, Date Location Research Method Field of Psychiatry Type of PrecisionModel Sample Level of Evidence Summary of Barriers
Summary of
Facilitators
Evanoff, 2016 [36] * United States Stakeholder meetings General psychiatry Genomics
Health care
professionals, research
scientists, and
community members
(n = unspecified)
1 Poor accuracy and utilityof the model
Engagement and
community outreach
Finn, 2005 [37] United States Survey General psychiatry Genetic testing
844 psychiatrists or
psychiatrists-in-
training
1
Potential stigmatisation;
Potential economic and
occupational harm; Lack
of clinical resources; Poor
perceived competence in
precision medicine
N/A
Goodspeed, 2019 [38] United States Focus groups andprototype development General psychiatry
Pharmaco-genomics
integrated into a
clinical decision
support system
16 mental health
clinicians 1
Poor perceived relative
advantage of the model;
Poor previous experience;
Cost and time
investments
Integration into current
workflow
Henshall, 2017 [39] United Kingdom Focus groups andprototype feedback General psychiatry
Clinical decision
support system
12 consultant
psychiatrists,
11 primary care
practitioners and
8 patients/carers
(n = 31)
1
Poor perceived relative
advantage of the model;
Potential psychological
harm; Poor transparency
and complexity of the
model; Cost and time
investments; Poor
accuracy and utility of the
model
Collaborative usage;
Trusting service
user/clinician
relationship;
Multi-modal models;
Simplicity and usability
of the model
Hoop, 2008 [40] United States Survey General psychiatry Genetic testing 45 psychiatrists 1
Lack of clinical resources;
Poor perceived
competence in precision
medicine
Availability of
associated
infrastructure
Hoop, 2010 [28] † United States Survey General psychiatry Pharmaco-genomics
75 psychiatry attending
physicians and
residents
1
Potential psychological
harm; Potential economic
and occupational harm;
Poor accuracy and utility
of the model; Cost and
time investments; Lack of
clinical resources;
Negative staff perceptions
of precision medicine
Confidentiality of
personal data;
Adequate skills and
competence training;
Availability of effective
interventions and
counselling
Illes, 2008 [41] United States Survey Major depression Functional brainimaging
52 psychiatrists or
psychologists, and
72 inpatient and
outpatient service users
(n = 124)
1
Cost and time
investments; Potential
psychological harm;
Potential economic and
occupational harm
N/A
Brain Sci. 2022, 12, 934 9 of 25
Table 2. Cont.
First Author, Date Location Research Method Field of Psychiatry Type of PrecisionModel Sample Level of Evidence Summary of Barriers
Summary of
Facilitators
Jenkins, 2016 [42] United Kingdom Face-to-face andtelephone interviews General psychiatry Genetic testing
9 psychiatric staff
nurses and consultant
psychiatrists
1
Poor transparency and
complexity of the model;
Poor accuracy and utility
of the model; Poor
perceived competence in
precision medicine; Weak
demand and engagement;
Potential psychological
harm; Potential
stigmatisation
Availability of
associated
infrastructure;
Adequate skills and
competence training
Laegsgaard, 2008 [43] Denmark Questionnaire General psychiatry Genetic testing 681 patients andrelatives 1
Potential misuse of
personal data; Scepticism
in genetics
Confidentiality of
personal data
Lucero, 2020 [44] * United States Survey General psychiatry Pharmaco-genomics 830 psychiatrists 1 N/A Adequate skills andcompetence training
Mathews, 2018 [24] *,† United States Feasibility study Child psychiatry Pharmaco-genomics
Parents and associated
clinicians of 73 young
service users
2
Cost and time
investments; Fear of
invasive procedures
Adequate skills and
competence training
Moreno-Peral, 2018 [29]
† Spain
Face-to-face
semi-structured
interviews
Major depression Individualised riskprediction algorithm 67 family physicians 2
Cost and time
investments; Poor
transparency and
complexity of the model;
Lack of motivation to
address mental health in
primary care; Potential
psychological harm
Simplicity and usability
of the model;
Stratification over
precision; Integration
into current workflow;
Adequate skills and
competence training;
Effective time
management and
organisation
Oliver, 2020 [25] † United Kingdom Feasibility study Clinical high-risk forpsychosis
Transdiagnostic risk
calculator
Clinicians of
3722 patients screened
and independent
consultation with an
unspecified number of
service users and
clinicians
2 N/A
Routinely collected
predictors; Outreach to
local clinicians and
clinical prompts
Reger, 2019 [26] † United States Case example Suicidal behaviours Clinical predictionmodel
A clinical
implementation team
of professionals
2
Lack of effective
interventions; Lack of
clinical resources
Outreach to local
clinicians and clinical
prompts; Compliance
with law and
regulatory pathways
Brain Sci. 2022, 12, 934 10 of 25
Table 2. Cont.
First Author, Date Location Research Method Field of Psychiatry Type of PrecisionModel Sample Level of Evidence Summary of Barriers
Summary of
Facilitators
Salm, 2014 [45] United States Survey General psychiatry Genetic testing
372 psychiatrists and
163 neurologists
(n = 535)
1
Potential misuse of
personal data; Poor
perceived competence in
precision medicine;
Potential psychological
harm; Potential economic
and occupational harm
Adequate skills and
competence training
Smith, 1996 [46] United States Survey Bipolar disorder Genetic testing
48 members of a bipolar
disorder support group,
35 medical students
and 30 psychiatry
residents (n = 113)
1 Lack of effectiveinterventions N/A
Trippitelli, 1998 [47] United States Questionnaire Bipolar disorder Genetic testing 90 service users andtheir spouses 1
Potential misuse of
personal data; Potential
stigmatisation; Potential
economic and
occupational harm
N/A
Wachtler, 2018 [48] Australia
Focus group, prototype
development and
semi-structured
interviews
Depression Clinical predictionmodel
17 members and of the
community and
7 service users (n = 24)
Poor transparency and
complexity of the
model;Ethics of risk
communication; Potential
psychological harm; Poor
accuracy and utility of the
model
Adaptability of the
model
Walden, 2015 [30] † Canada Survey General psychiatry Pharmaco-genomics
168 physicians who
had ordered
pharmaco-genomic
tests for psychotropic
medication
1 Negative staff perceptionsof precision medicine N/A
Wilde, 2010 [49] Australia Focus groups Major depression Genetic testing
36 members of the
public (14 with
disclosure of family
history of mental
illness)
1
Poor perceived relative
advantage of the model;
Poor accuracy and utility
of the model; Potential
misuse of personal data;
Lack of effective
interventions; Potential
psychological harm;
Potential stigmatisation;
Potential economic and
occupational harm
Integration into
workflow
Brain Sci. 2022, 12, 934 11 of 25
Table 2. Cont.
First Author, Date Location Research Method Field of Psychiatry Type of PrecisionModel Sample Level of Evidence Summary of Barriers
Summary of
Facilitators
Williams, 2016 [50] United States Semi-structuredinterviews Alcohol use disorders Genetic testing
24 primary care
providers 1
Cost and time
investments; Poor
accuracy and utility of the
model; Lack of clinical
resources; Negative staff
perceptions of precision
medicine; Potential
psychological harm
Patient engagement
Zhou, 2014 [51] Australia Survey
Schizophrenia, bipolar
disorder and major
depression.
Genetic testing
104 psychiatrists, 36
genetic counsellors,
and 17 medical
geneticists (n = 157)
1
Poor perceived
competence in precision
medicine; Potential
economic and
occupational harm
N/A
Records marked with * represent a conference abstract; all other records are full journal publications. Records marked with † represent those employing actual implementation methods
as opposed to hypothetical or simulated implementation. Quality ratings: 3 = Randomized Controlled Trials, 2 = Pilot and feasibility studies, 1 = All other primary research involving
stakeholder consultation. AI = Artificial Intelligence; CDS = Clinical Decision Support; ML = Machine Learning.
Brain Sci. 2022, 12, 934 12 of 25
Brain Sci. 2022, 12, x FOR PEER REVIEW 8 of 30 
 
constructs [23]. Table 2 offers a detailed breakdown of the characteristics of the included 
studies. 
 
Figure 4. The precision psychiatry approaches adopted across the included literature and the pro-
portion (%) of studies investigating each approach. 
0 5 10 15 20 25 30 35 40 45
Genetic testing
Pharmacogenomics
Clinical prediction models and risk…
Clinical decision support systems
Functional brain imaging
General AI/ML approaches
Proportion of studies (%)
Precision Approaches
Figure 4. The precision psychiatry approaches adopted across the included literature and the
proportion (%) of studies investigating each approach.
3.3. Level of Evidence Summary
As no RCT’s were identified during the review process, no records were assigned a
higher-grade score of 3. Seven records (25.0%) were assigned a mid-grade quality score of
2, and the remaining 21 (75.0%) records were assigned a lower-grade score of 1.
3.4. Factors Affecting the Implementation of Precision Psychiatry
We identified a broad variety of factors which covered each of the key CFIR constructs.
Figure 5 provides a high-level visual summary of the identified barriers and facilitators
corresponding to each of these constructs and the reported frequencies of each factor are
presented in Figure 6 (barriers) and Figure 7 (facilitators).
Brain Sci. 2022, 12, x FOR PEER REVIEW 16 of 30 
 
 
Figure 5. A high-level visual summary of the identified barriers and facilitators which may impact upon the real-world implementation of precision psychiatry 
approaches, structured according to the Consolidated Framework for Implementation Research (CFIR). 
Figure 5. A high-level visual summary of the identified barriers and facilitators which may impact
upon the real-world implementation of precision psychiatry approaches, structured according to the
Consolidated Framework for Implementation Research (CFIR).
Brain Sci. 2022, 12, 934 13 of 25
Brain Sci. 2022, 12, x FOR PEER REVIEW 17 of 30 
 
 
Figure 6. Proportion (%) of the included studies reporting each barrier.  
 
Figure 7. Proportion (%) of the included studies reporting each facilitator. 
3.4.1. Characteristics of the Model 
Of the included studies, 57.1% (n = 16) reported barriers or facilitators relating to par-
ticular characteristics of the precision model which may impact upon implementation. 
Barriers 
Figure 6. Proportion (%) of the included studies reporting each barrier.
Brain Sci. 2022, 12, x FOR PEER REVIEW 17 of 30 
 
 
Figure 6. Proportion (%) of the included studies reporting each barrier.  
 
Figure 7. Proportion (%) of the included studies reporting each facilitator. 
3.4.1. Characteristics of the Model 
Of the included studi s, 57.1% (n = 16) reported barriers or facilitators relating to par-
ticular characteristics of the precisio  model which m y impact upon implementati n. 
Barriers 
Figure 7. Proportion (%) of the included studies reporting each facilitator.
3.4.1. Characteristics of the Model
Of the included studies, 57.1% (n = 16) reported barriers or facilitators relating to
particular characteristics of the precision model which may impact upon implementation.
Barriers
1. Cost and time investments
Logistical and practical barriers associated with cost and time investments of the
prediction model were the most highly reported barrier within this construct (n= 9; 32.1%).
They were almost exclusively reported by health care professionals as opposed to any
Brain Sci. 2022, 12, 934 14 of 25
other stakeholder groups. In particular, the potential financial burden and high costs
associated with the implementation of the precision model were highly reported as bar-
riers [24,28,33,39,41,50] alongside the need for data to highlight cost-effectiveness before
widespread implementation can be considered [39]. Concerns surrounding time invest-
ments were also identified, including the use of time-intensive tools within a small consul-
tation window [27–29,38,39], slow computational speed of electronic tools [38], and lengthy
waiting times for results [24,33,50]—particularly regarding patients who are acutely un-
well [27]. Some physicians reported that the use of a risk prediction model also required
more effort to implement than standard practice and led to more frequent patient visits,
though this was rebutted by other physicians across a series of interviews [29]. Furthermore,
clinicians also highlighted the challenging aspects of alert systems embedded into precision
medicine tools and emphasized the need to distinguish between alerts which are clinically
useful and those which are not in order to avoid alert fatigue and optimize efficient use of
time [38].
2. Poor accuracy and utility of the model
A further highly reported thematic group of barriers (n = 8; 28.6%) within this construct
related to the predictive accuracy and clinical utility of the precision model. These barriers
were also largely reported by health care professionals, and included concerns relating
to the substantial margin of error in risk prediction [48], the potential for false-negative
outcomes [32], and poor predictability and prognostic accuracy beyond current working
practice [36,42,49,50]. Furthermore, there were additional challenges raised with respect to
the lack of strength of current evidence [39,50], and the corresponding need for published
peer-reviewed supportive evidence [28].
3. Poor perceived relative advantage of the model
Challenges surrounding the relative advantage of the precision model were also
frequently highlighted (n = 5; 17.9%). Several studies reported stakeholder beliefs that the
precision model offered no advantage beyond current clinical care and risked the potential
of being implemented at the expense of clinical judgement [27], could pose greater general
risks compared to current care [34], did not reflect the complexities of clinical consultation,
and could not capture the more nuanced and fine-grained factors that are only available
through human interaction which might usually influence the clinical decision-making
process [39]. In some instances, testing was only deemed to be advantageous for particular
subgroups of service users who might benefit most and as such was only reserved for
these select groups, such as those with a family psychiatric history [49], poor treatment
responders or those with more atypical symptom presentations [38].
4. Poor transparency and complexity of the model
Several studies also reported challenges relating to the technical complexity of the
precision model (n = 5; 17.9%) and the corresponding difficulty in translating these concepts
to a layperson or to a population with reduced cognitive capacity, therefore highlighting the
poor adaptability of the tool to perform equally well with a range of recipients. Specific bar-
riers were identified regarding the lack of transparency over the underlying algorithm and
which factors statistically contributed most to a high-risk outcome [32], overly medicalized
language [39], the numerical output of a tool in conjunction with low numerical literacy
across the population [48], difficulties understanding and communicating the concept of
risk prediction [29], and subsequent ethical concerns surrounding capacity to consent to
treatment decisions [39,42].
5. Lack of clear guidelines
Finally, a lack of clear guidelines to govern use of the precision model was raised by just
one study (3.6%) in relation to the usage of pharmacogenomic methods [33], highlighting
corresponding guidance documentation as an important aspect of implementation.
Brain Sci. 2022, 12, 934 15 of 25
Facilitators
6. Simplicity and usability of the model
Two studies (7.1%) placed emphasis upon the importance of a precision model which is
both simple and quick to use [29,39], with a range of health care professionals highlighting
that a time-saving tool is more likely to be used in practice, particularly in light of typically
narrow clinical consultation periods.
7. Collaborative usage
In one study (3.6%), health care professionals also called for patient-facing precision
tools, stating that they promote collaboration and build trust between the health care
professional and the service user [39].
8. Adaptability of the model
In order to overcome issues surrounding model complexity and poor adaptability
(discussed above in Section 3.4.1), one prototype development study (3.6%) reported that
patient-facing tools require an emphasis upon clear communication and offered pictorial
format as a potential solution [48].
9. Stratification over precision
The way in which the outcome of a precision model was delivered was also of im-
portance, with health care professionals favoring stratified outcome prediction (e.g., low-
, medium-, and high-risk) rather than individualized, numerical figures in one study
(3.6%) [29].
10. Multi-modal models
Precision models utilising multi-modal data were also raised as a potential facilitating
factor in one study (3.6%), as clinicians expressed interest in multi-modal models involving
the integration of biological data with lifestyle factors to increase accuracy [39].
11. Routinely collected predictors
Finally, one study (3.6%) highlighted the preferred use of factors which are routinely
collected in clinical practice as these are better suited to more seamless implementation [25].
3.4.2. Inner Setting
One half of the included literature (n = 14; 50%) reported factors relating to features of
the inner setting.
Barriers
12. Lack of clinical resources
The absence or limited availability of local resources was raised as a challenge by
a range of health care professionals across six studies (21.4%). Resources which were
particularly highlighted included insufficient laboratory facilities [50], and a lack of pre-
and post-test genetic counselling [28], with only 13% of surveyed psychiatrists aware of
professionals offering genetic counselling locally [40]. The need for sufficiently skilled
coordinating staff to oversee implementation was also raised as a limiting factor [26]. In
line with the challenging financial costs associated with implementation discussed above
(Section 3.4.1), there were also concerns reported with regards to budget reallocation [27],
particularly away from psychosocial therapies [37].
13. Lack of effective interventions
Furthermore, the lack of appropriate and effective interventions or treatments in the
case of a high-risk outcomes or positive genetic test was identified across several studies
(n = 3; 10.7%) [26,46,49]—in fact, one study reported a substantial decline in interest in
hypothetical genetic testing when corresponding treatments were unavailable [46].
Brain Sci. 2022, 12, 934 16 of 25
Facilitators
14. Availability of associated infrastructure
Several studies (n = 4; 14.3%) reported the need for precision models, particularly genetic
testing and pharmacogenomics, to be offered directly through specialist providers [35,40,42].
Clinicians further highlighted the need for wider availability of testing and related infras-
tructure to optimize implementation [33].
15. Integration into current workflow
The seamless integration into current workflow was also highlighted as a facilitator
within three studies (10.7%) [29,38], including suggestions of improved integration of
genotyping into primary care and general health check-ups [49].
16. Availability of effective interventions and counselling
Finally, health care professionals and service users alike highlighted the local availabil-
ity of subsequent, appropriate intervention in the event of a high-risk outcome [31] and pre-
and post-test counselling provisions for genetic testing as facilitating factors [28] across
two studies (7.1%).
3.4.3. Outer Setting
One quarter of the included literature (25.0%; n = 7) identified barriers or facilitators
relating to features of the outer setting which may impact upon implementation.
Barriers
17. Potential misuse of personal data
The barriers identified in relation to the outer setting were largely associated with
safety and security concerns (n = 4; 14.3%) regarding the potential for the misuse of personal
data by external stakeholders and third parties. Such challenges were most commonly re-
ported by service users as opposed to other stakeholder groups. A number of genetic-based
studies reported the misuse of private genetic data by third-parties as a potential barrier,
particularly if the data were available to employers or insurance companies [43,45,47,49].
This was specifically highlighted for direct-to-consumer genetic testing [49].
18. Ethics of risk communication
Additionally, general ethical concerns were also reported in one study (3.6%) with re-
gards to using risk communication tools as a ‘persuasive mechanism’ to influence decision-
making [48].
Facilitators
19. Confidentiality of personal data
Health care professionals and service users alike emphasized the need for the confi-
dentiality of genetic data and the outcome of genetic tests across two studies (7.1%) [28,43].
20. Compliance with law and regulatory pathways
Finally, continued compliance with applicable law, regulations and safety planning
was also acknowledged as a factor in a single study (3.6%) to improve the ethical imple-
mentation of a prediction model [26].
3.4.4. Characteristics of the Individuals—Staff
Characteristics of health and social care staff were highly reported as potential barriers
and facilitators to the implementation of precision psychiatry methods, with 62.07% (n = 18)
of the included literature reporting at least one factor relating to this construct.
Brain Sci. 2022, 12, 934 17 of 25
Barriers
21. Negative staff perceptions of precision medicine
Negative staff perceptions of the usefulness and applicability of precision psychiatry
were commonly reported (n = 6; 21.4%), particularly with regards to genetic testing and
genomics. Across the literature, there was a general sense that genomics in psychiatry was
still in its infancy and as such, testing was not currently clinically useful [28], with other
professionals reporting that tests were not ready for routine implementation and were only
currently applicable in academic research settings [33]. Limiting factors to the perceived
usefulness of such testing were also reported; whilst health care professionals reported inter-
est in hypothetical tests with high predictive power, this interest dropped substantially for
tests with moderate prognostic/predictive power [35]. Doctors generally expressed more
concern about the accuracy of pharmacogenomic testing compared with pharmacists [33],
and other professionals perceived testing as only useful under specific circumstances (e.g.,
treatment resistance) [33]. Furthermore, clinicians also expressed concern of the potential
impact of precision models upon the staff-service user dynamic, citing that precision psy-
chiatry may offer less personal and empathic care compared with current clinical care [34].
Several studies also highlighted important discrepancies in attitudes across different clinical
professions. For example, clinical scientists held significantly more favourable attitudes
towards pharmacogenomic testing compared with core psychiatrists [30], and professionals
who were less comfortable with prescribing pharmacological interventions for alcohol use
disorders acknowledged that this would limit the likelihood of using genetic testing to
guide treatment decisions [50].
22. Poor perceived competence in precision medicine
Poor perceived competence and abilities of health care professionals was frequently
reported as a barrier (n = 7; 25.0%), most commonly in relation to genomics and genetic
testing. A survey of health care professionals highlighted general poor perceived compe-
tency in pharmacogenomics, with pharmacists generally reporting higher competence than
doctors across various aspects of pharmacogenomics [33]. Several further studies reported
low confidence in skills and knowledge surrounding genetic testing and feelings of being
ill-equipped or inadequately trained to discuss genetic information [37,42,45,51], with just
9% of respondent clinicians feeling competent to offer genetic testing and interpret the
results [40], thus raising the possibility that a more formal specialized clinical service is re-
quired [42]. However, two further studies reported that the majority of medical geneticists
and genetic counsellors surveyed had not received any training in psychiatric genetics [51]
and there was a lack of familiarity of such tests among laboratory staff [27], suggesting this
is a system-wide issue across various environments and professionalisms.
23. Poor previous experience
Poor previous experience with precision medicine methods was also reported as
an obstacle within a single study (3.6%) and was reported to result in more widespread
negative perceptions of precision medicine methods; for example, several clinicians voiced
skepticism over the accuracy of a clinical decision support tool based largely on poor
previous experience with similar systems [38].
24. Lack of motivation to address mental health in primary care
Within a single study (3.6%), primary care professionals emphasized a lack of motiva-
tion to address mental health problems within primary care settings, resulting in poorer
engagement with the implementation process in this environment [29].
Facilitators
25. Adequate skills and competence training
The reported facilitators across this construct related almost entirely to competent,
knowledgeable, and skilled staff in combination with the corresponding availability of
Brain Sci. 2022, 12, 934 18 of 25
education and training; this was also the most highly reported overall facilitator (n = 7;
25.0%). In particular, facilitators included staff who were competent in communication and
in interpreting the results of the precision model [28,29,31]. Health care professionals high-
lighted the need for more extensive and continuous training in communication skills [29,31],
interpreting the outputs of a precision model [28,29], statistical methods [45], genetics and
familial risks [42], and case-specific training and feedback [24]. One study identified that
improved competence and knowledge in pharmacogenomics led to improved confidence
amongst psychiatrists [44], whilst another study reported that accrued clinician experience
in the implementation of a risk calculator improved skills [29].
26. Effective time management and organization
Finally, effective schedule management and organization of physicians was identified
(n = 1; 3.6%) as a mitigating factor against the potential time investment of implementing a
new precision model [29].
3.4.5. Characteristics of the Individuals—Service Users and Families/Caregivers
Similarly, the characteristics and needs of the potential service users (and fami-
lies/caregivers) were also highly reported as barriers or facilitators to the implementation of
precision psychiatry, with 64.3% (n = 18) reporting at least one factor within this construct.
Barriers
27. Potential psychological harm
The most commonly reported barrier within this construct (n = 11; 39.3%), and indeed
the most commonly reported overall barrier by a range of stakeholders, was the potential
for an adverse psychological impact upon the service user. The potential for psychological
harm was widely discussed [28,33,42], including the possible anxiety-inducing effects
of risk prediction [27,29,39,41,45], the risk for fatalistic thinking or an exacerbation of
depressive symptoms following a high-risk outcome [48,49], and subsequent decreased
motivation [50].
28. Potential economic and occupational harm
Further adverse impacts upon the service user and their families were also widely
considered, including the potential for economic and occupational harm (n = 8, 28.6%).
Challenges included the potential for general economic harm [33] and the denial of in-
surance [28,37,47,51], concerns over privacy [45,49], potential genetic discrimination and
inadequate legal support for such discrimination [45,49], and employment discrimina-
tion [28,37,41].
29. Potential stigmatization
Similarly, adverse social effects were also raised by several studies (n = 4; 14.3%), such
as possible stigmatization [42,49], potentially unwarranted concerns for offspring [47], and
lowered expectations for children carrying a high-risk gene [37].
30. Skepticism regarding genetics
There was also a sense of skepticism of psychiatric genetics across the literature
(n = 2; 7.1%); those who believed that mood disorders were predominantly caused by genes
were significantly more interested in genetic testing than those who placed more emphasis
on the causative nature of life experiences [35], with some participants opposing genetic
testing completely [43], and concerns that prenatal genetic testing would impact upon
decisions surrounding pregnancy [35].
31. Negative attitudes towards psychiatry
One study (3.6%) identified general negative attitudes towards psychiatry and a deep
mistrust in the psychiatric profession amongst service users as a challenging barrier to
overcome [31].
Brain Sci. 2022, 12, 934 19 of 25
32. Resistance to knowing risk scores
A resistance to knowing risk scores for major depression was raised as a barrier
amongst service users within one study (3.6%), particularly compared to physical health
conditions; crucially, this was discussed in light of the lack of definitive preventive treatment
available for depression [31].
33. Fear of invasive procedures
Just one study (3.6%) identified specific phobias relating to precision methods as a
challenging factor, such as the fear of needles involved in genetic testing [24].
34. Weak demand and engagement
Further negative perceptions and attitudes towards services were raised as barriers
in one study (3.6%), including weak service user demand for genetic psychiatry services,
poor service user engagement with the service and negative past experiences with similar
services [42].
Facilitators
35. Service user engagement
Patient engagement was highlighted as a facilitating implementation factor in one
study (3.6%), with a potential positive impact reported upon compliance, motivation and
adherence to treatment [50].
36. Trusting service user/clinician relationship
A further study (n = 1; 3.6%) also reported that a trusting relationship between the
health care professional and the service user is essential, and was posited to improve
compliance [39].
3.4.6. Implementation Process
Just 10.7% (n = 3) of the included literature reported factors relating to the actual
process of implementation. No barriers were reported in relation to the implementation
process, but this was secondary to the dearth of actual implementation studies within the
psychiatric literature.
Facilitators
37. Outreach to local clinicians and clinical prompts
Facilitators involved in the implementation process exclusively related to engagement
and outreach to local professional and public communities. Two implementation studies
(7.1%) reported an improved implementation process when clinician prompts and outreach
activities were conducted [25,26]. Further, the content of clinical prompts was also of
importance, with a raised response rate reported when the patient names were used instead
of internal identification number usage [25].
38. Engagement and community outreach
Finally, the critical importance of service user and public involvement initiatives
and public education surrounding the use of genomics was highlighted in a single study
(3.6%) [36].
4. Discussion
This large-scale review demonstrates several key strengths; we implemented a wide-
reaching and inclusive search strategy to ensure a variety of literature from various aca-
demic fields was captured. Furthermore, no limitations were placed on date of publication,
geographical location and manuscript language, ensuring we identified research from a
variety of precision approaches and geographies. To our knowledge, this is also the first sys-
tematic review to identify factors affecting the implementation of global precision methods
Brain Sci. 2022, 12, 934 20 of 25
in psychiatry. These factors represent a framework of key considerations to address during
both the development and implementation of precision prediction models in psychiatry
and as such, will be of use to a wide range of professionals, from research scientists to
health care professionals and policymakers alike. In particular, a number of key findings
may help to shape protocols for future implementation science.
4.1. Key Findings
The current literature identified a range of barriers, and a narrower selection of facili-
tators, highlighting the numerous and widespread challenges which may be encountered
during the implementation process. The most highly reported barriers covered a range of
issues, such as ethical considerations, logistical challenges, and attitudinal perceptions of
key stakeholders, thus demonstrating that there is no singular challenging factor to over-
come for successful implementation. In particular, we identified five barriers which were
most commonly reported across the literature: (i) Potential psychological harm (n = 11),
(ii) Cost and time investments (n = 9), (iii) Potential economic and occupational harm
(n = 8), (iv) Poor accuracy and utility of the model (n = 8), (v) Poor perceived competence in
precision medicine (n = 7), and one facilitator: (i) Adequate skills and competence training
(n = 7).
First, the potential adverse effect of precision methods upon the service users’ psy-
chological wellbeing was identified across much of the literature. The potential negative
psychological effects of receiving a high-risk outcome received particular consideration due
to the potential for fatalistic thinking and fear of the future, alongside the subsequent poten-
tial social implications such as stigmatization. This is a particularly pertinent consideration
given the lack of definitive testing currently available in psychiatry. This topic has received
much debate across psychiatry, law and bioethics—particularly in relation to psychosis
risk [52,53]. Although qualitative research suggests that such risk labels may have an
impact upon the sense of self and social stigma [54–57], these adverse effects are lessened
when participants are fully informed of the meaning of ‘at-risk’ [57,58]. This highlights the
crucial importance of training staff to interpret and discuss the output of risk prediction
models, and appropriately feed this information into the clinical decision-making process.
Moreover, qualitative explorations with young people at-risk have actually highlighted the
therapeutic effects of sharing their experiences within specialist services [59,60]. Indeed,
there is a wide range of vocational, psychosocial and familial support interventions which
are offered through such specialist services which might not otherwise be made available
to the individual [61]. Further recent research has also disputed the adverse social impact
of a psychosis-risk label [58], and recent evidence suggests that the presence of stigma is
actually associated with the service users’ experiences of distressing symptoms as opposed
to the clinician’s designation [54].
Second, this review also identified various logistical challenges, particularly sur-
rounding the high financial cost of implementing precision models compared to current
psychiatric care. This finding necessitates a greater research focus on economic modelling
of such approaches, particularly high-cost methodologies such as magnetic resonance imag-
ing, in order to determine cost-effectiveness. Similarly, a range of health care professionals
highlighted the facilitating nature of precision models which are quick and easy to use in
practice, suggesting that this aspect needs to be given greater weight in model development
rather than building complex, multi-modal models which may be more challenging to
implement in practice. However, in contrast, one included study identified the integration
of multi-modal biological data as a facilitating factor [39]. This suggests that model de-
velopment requires a trade-off to find balance between model simplicity and predictive
accuracy. Ultimately, these findings reinforce the notion that precision psychiatry models
should be developed with such logistical challenges in mind.
Third, numerous included studies also discussed the potential adverse financial and
occupational impact of precision models in relation to insurability and employment of the
service user, although, a significant proportion of the studies reporting this barrier were
Brain Sci. 2022, 12, 934 21 of 25
derived from research undertaken in the United States [28,37,41,47], and so this challenge
may require more substantial consideration within countries adopting an insurance-based
health care system. Nevertheless, the frequent reporting of these concerns may also reflect
widespread mistrust in personal data security and emphasizes the need to place priority on
the safety and security of data, particularly as data-driven health care continues to build at
pace, globally. Taken together with the highly-reported concerns regarding psychological
wellbeing discussed above, it will be imperative within ongoing research efforts to develop
an ethical framework for the implementation of preventive psychiatry approaches in close
collaboration with the key stakeholder groups outlined in this review—with a particular
focus on service users and their families to ensure further research ‘optimizes benefit and
minimizes harm’ [61].
Fourth, challenges regarding poor clinical utility and accuracy were highly reported.
Indeed, our recent review [6] reported highly variable rates of prognostic/predictive
accuracy across precision psychiatry models within the literature, and further identified a
high risk of bias across 94% of the models (according to the PROBAST [62] tool). Moreover,
due to a lack of external validation efforts present across much of the literature [6,63],
it is difficult to assess the real-world utility of many existing clinical prediction models.
Thus, in order to progress in this field, a shift towards further external validation and
implementation is needed. Recent studies have started focusing on the external replication
of existing clinical prediction models in the field of psychosis risk, and should be followed
by similar initiatives in other fields [64].
Finally, we identified a substantial proportion of records reporting poor perceived
competence and knowledge amongst staff in precision medicine, with a particular focus on
genetic testing and pharmacogenomics. Whilst there is evidence of substantial progress
in genomic education amongst medical professionals in recent years [65,66], this current
review suggests that a more tailored approach may be required within psychiatry. In
parallel, it is unsurprising that the most highly reported facilitator across the literature
was the immediate need for greater provision of training and education amongst staff,
especially in relation to genetics and pharmacogenomics. This was similarly reflected
within a recently developed implementation plan for general precision medicine informed
by stakeholder views [17] and reiterates the importance of frequent adjustments to national
medical training and teaching curricula to reflect recent scientific advances, as recently
argued by our group [2].
Overall, these key findings provide a tentative empirical platform to guide future
implementation research and ensure that model development and validation activities take
implementation into account from the very early stages. It is commonplace within research
that implementation barriers are considered too late, when the model is already developed
and validated, leading to the frequent development of tools which are impractical to
implement in practice. As such, these current findings will be of interest to research
scientists as well as policymakers who must ensure that implementation activities are
sufficiently regulated by a comprehensive legal framework. Finally, this research may be of
importance to the end-users of such innovation: health care professionals and service-users.
4.2. Limitations and Future Directions
Whilst this review covered a comprehensive range of literature, it also highlighted
numerous current gaps in the literature base which necessitate further research attention.
No studies were identified which assessed the perspectives of policymakers; in light of their
integral role in the provision and regulation of health care, it will be important to gather
their perspectives in future research. Furthermore, the majority of our results were based
upon qualitative literature. However, the nuance and detail which arises from qualitative
research is essential to move forward in this field and the qualitative synthesis presented
here was best suited to the available literature.
Brain Sci. 2022, 12, 934 22 of 25
Finally, this review also reiterated the sparsity of implementation studies for precision
methods in the field of psychiatry, previously acknowledged in a recent review [6]. As such,
‘Process’ factors were limited within the included literature, with no barriers reported for
this CFIR construct. This highlights an important gap in the research and necessitates a
focus on translational research fit for implementation in order to establish a high-quality
evidence base in support of precision psychiatry. Whilst a RCT was recently published
which assessed the clinical effectiveness of a predictive algorithm to guide antidepressant
treatment [67], it does not meet inclusion criteria for this review. However, qualitative
experiences of this trial are due to be reported separately and may offer higher-grade evi-
dence of the barriers and facilitators to real-world implementation of precision psychiatry.
Meanwhile, at present there are a variety of established implementation frameworks and
guidelines, beyond the CFIR [23], which can support implementation efforts across the field,
such as the Normalization Process Theoretical Framework [68], the FAIR principles [69],
the RE-AIM framework [70], and the Expert Recommendations for Implementing Change
(ERIC) project [71], as well as existing systematic reviews regarding other related fields of
innovation in psychiatry, such as digital and eMental Health [72,73].
5. Conclusions
A diverse range of barriers exist which may impede the translation of precision psy-
chiatry research findings into real-world clinical care; these barriers should be taken into
consideration during the early development stages of such models and corresponding
pragmatic and innovative solutions are required at the level of the individual, the organiza-
tion and the wider system. Ongoing community engagement initiatives are essential to
address negative perceptions amongst stakeholders, and specialized medical educational
modules in precision methods are required to equip health care staff with the knowledge
and skills needed to confidently employ precision methods in practice. Finally, this review
has highlighted the vital need for further implementation research, education and training.
In particular, future research should prioritize the initiation of randomized controlled trials
of precision models in order to successfully translate precision psychiatry research from
the ‘bench to bedside’.
Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/brainsci12070934/s1, Table S1: PRISMA 2020 Statement and
Checklist; Methods S1. Systematic Search Strategy; Methods S2. Data Extraction Categories
Author Contributions: Conceptualization, H.B., D.O., G.S.d.P., D.S. and P.F.-P.; methodology, H.B.;
validation, L.L.-D.; formal analysis, H.B. and L.L.-D.; writing—original draft preparation, H.B. and
P.F.-P., writing—review and editing, H.B., L.L.-D., D.O., G.S.d.P., D.S., H.R. and P.F.-P., visualization,
H.B., supervision, P.F.-P., project administration, H.B. All authors have read and agreed to the
published version of the manuscript.
Funding: This research was funded by a National Institute for Health Research (NIHR) Maudsley
Biomedical Research Centre doctoral scholarship awarded to H.B.
Institutional Review Board Statement: Not applicable” for studies not involving humans or animals.
Informed Consent Statement: Not applicable.
Acknowledgments: H.B. is supported by a National Institute for Health Research (NIHR) Maudsley
Biomedical Research Centre doctoral studentship. D.S. also received financial support by the National
Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley
NHS Foundation Trust and King’s College London. The views expressed are those of the author(s)
and not necessarily those of the NHS, the NIHR or the Department of Health. G.S.d.P. is supported
by the Alicia Koplowitz Foundation.
Conflicts of Interest: The authors declare no conflict of interest.
Brain Sci. 2022, 12, 934 23 of 25
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