Patient Decision Aid (PDA) for Antidepressant Use In Pregnancy: a Pilot RCT
Phase: NA
Conditions: Depression, Pregnancy
Sponsor: King's College London

King’s Clinical Trials Unit 
 
Confidential 
Confidentiality and Copyright: This document is confidential and property of King’s Clinical Trials Unit. This document may not be 
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1. PROTOCOL FULL TITLE 
Protocol Short Title/ Acronym: 
Patient Decision Aid (PDA) for Antidepressant Use In Pregnancy: a pilot RCT  
 
Trial Identifiers  
ClinicalTrials.gov 
identifier  
NCT02492009 
REC Number: 
15/LO/0601 
UKCRN Number: 
19051 
Protocol Version 
Number: 
 2 
Date: 
22/01/2016 
 
(Co) Sponsor(s) 
 
Name: 
KCL (lead sponsor), SLAM (co-sponsor) 
Address: 
Keith Brennan Director of Research Management 
Director of Administration (Health Schools) 
Room 1.8 Hodgkin Building 
Guy's Campus 
King's College London 
London SE1 4UL 
Telephone: 
020 7848 6960 
Fax: 
 
Email: 
keith.brennan@kcl.ac.uk 
 
Chief Investigator  
Name: 
Professor Louise Howard 
Address: 
Section of Women’s Mental Health, PO31 King’s College London, De Crespigny 
Park, London SE5 8AF 
Telephone: 
02078485061 
Fax: 
02072771462  
Email: 
louise.howard@kcl.ac.uk 
 
 

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Name and address of Co-Investigator(s), Statistician, Therapy Service, Laboratories 
etc 
Name: 
Dr Hind Khalifeh 
Position/ Role: 
Senior clinical researcher and consultant psychiatrist; co-investigator 
Address: 
Section of Women’s Mental Health, PO31 King’s College London, De Crespigny 
Park, London SE5 8AF 
Telephone: 
02078485061 
Fax: 
02072771462  
Email: 
hind.khalifeh@kcl.ac.uk 
 
Name: 
Dr Simone Vigod 
Position/ Role: 
Assistant Professor and Consultant Psychiatrist; co-investigator 
Address: 
Department of Psychiatry and Institute of Health Policy, Management and 
Evaluation, Faculty of Medicine, University of Toronto 
Telephone: 
001- 416-351-3732 
Fax: 
 
Email: 
Simone.vigod@wchospital.ca 
 
2. Study Synopsis 
TITLE OF CLINICAL TRIAL: 
Patient Decision Aid (PDA) for Antidepressant Use In 
Pregnancy: a pilot randomised controlled trial 
Protocol Short Title/ Acronym: 
PAUSE-P 
Study Phase If Not Mentioned In 
Title: 
 
Sponsor Name: 
King’s College London and South London and Maudsley NHS 
Foundation Trust 
Chief Investigator: 
Professor Louise Howard 
UKCRN Number: 
19501 
REC Number: 
15/LO/0601 
Medical Condition Or Disease 
Under Investigation: 
Depression in pregnancy 

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Purpose Of Clinical Trial: 
The proposed study is a pilot randomized controlled trial (RCT) 
of an electronic patient decision aid (PDA) for antidepressant 
use in pregnancy. The overall aim of this pilot RCT is to 
establish the feasibility of future large international RCT of the 
PDA’s effectiveness. 
Primary Objective: 
The primary objective of this pilot is to assess the feasibility of 
the trial protocol; measured through three components: (1) 
feasibility (how well the trial protocol can be implemented), (2) 
acceptability (usability and tolerability of the intervention and of 
randomisation including patient and provider views) and (3) 
adherence (the degree to which the trial protocol is followed). 
Secondary Objective(s): 
The secondary objective is to inform sample size calculations for 
a future RCT by obtaining potential estimates of the PDA’s 
efficacy (in terms of the primary outcome of decisional conflict, 
and the secondary outcomes of knowledge about treatment 
options, participant-provider interaction and depressive / anxiety 
symptoms at follow-up).  
Trial Design: 
Pilot parallel-group investigator-blinded RCT 
Endpoints: 
The primary outcome for this pilot study is the feasibility of 
conducting a large RCT to evaluate the efficacy of the PDA; 
assessed in terms of (a) feasibility of the trial protocol, (b) 
acceptability of the intervention and randomisation procedures to 
patients and clinicians and (c) adherence with the trial protocol.  
Secondary outcomes, which will generate preliminary effect 
sizes of the PDA and inform sample size calculations for the 
future RCT, include: Decisional Conflict Scale1, Knowledge 
Questionnaire (adapted from Metcalfe et al)2, Edinburgh 
Postnatal Depression Scale (EPDS)3, Spielburg State-Trait 
Anxiety Inventory (STAI)4 and the OPTION Scale measure of 
shared decision-making5. A brief topic guide will also be used to 
qualitatively analyse the audiotaped clinical follow-up 
appointment.6 
Sample Size: 
50 (25 per arm) 
Summary Of Eligibility Criteria: 
Women are eligible to participate if they meet all of the following 
inclusion criteria: (a) aged over 18, (b) are planning a pregnancy 
or are <30 weeks pregnant at enrolment, (c) have been offered 
to start or continue an antidepressant as treatment for 
depression by their clinician and (d) have moderate-to-high 
decisional conflict (score of >25 on the Decisional Conflict 
Scale). Women will be excluded from the study if they meet any 
of the following exclusion criteria: (a) have had alcohol or drug 
abuse or dependence in the previous 12 months, or (b) have 
active suicidal ideation or psychosis, or (c) are incapable of 
consenting to participation, or (d) have any major obstetric 
complications or foetal cardiac anomaly in the current or in a 
past pregnancy, or (e) are visually impaired) or (f) do not have 
sufficient English language proficiency to use the PDA. 
Intervention (Description, 
frequency, details of delivery) 
Women allocated to the intervention arm will log in to the study 
website and receive access to an electronic patient decision aid 
(PDA) on antidepressant use in pregnancy. They will have 
access to the website until their final follow-up or until the end of 
the main study period, during which time they can use the PDA 
as often as they would like at a time and place that suits them, 

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alone or with others (e.g. family, friends). They can choose the 
amount of complex information that they want to access and 
read (by clicking on ‘further information’ links). They will also 
have access to a printable PDF containing references to 
standard published information and resources on antidepressant 
use in pregnancy (see Appendix). 
Comparator Intervention: 
Women allocated to the comparator intervention will log in to the 
study website and receive access to a printable PDF containing 
references to standard published information and resources on 
antidepressant use in pregnancy (see Appendix). They will have 
access to the website until their final follow-up or until the end of 
the main study period. 
Maximum Duration Of Treatment Of 
A Subject: 
All participants will have access to the study website until their 
final follow-up or until the end of the main study period. They will 
be asked to make a follow-up appointment with their clinician 
within 4 weeks of randomisation.  They will have follow-up 
assessments at two time points: (1) 4 weeks post-randomization; 
and (2) either 12 weeks postpartum (if the participant enrolled 
while pregnant) or 6 months post-randomization (if the 
participant enrolled while planning a pregnancy). Therefore, the 
overall duration of participation in the study is up to one year. 
Version And Date Of Final Protocol: 
Version 1, date 9/2/2015 
Version And Date Of Protocol 
Amendments: 
Version 2, date 22/01/2016 
 
 
3. Revision History 
Document ID - (Document 
Title) revision X.Y 
Description of changes from previous revision 
Effective Date 
UK_PDA_Protocol v1  
9/2/2015 
New Protocol 
03/06/2015 
UK_PDA_Protocol_v2 
22/01/2016 
Change to national recruitment via self-referral from 
online advertising and information provided to relevant 
clinicians  
 
 
 
 
4. Glossary of terms (Optional) 
 
 
 
 
 
 

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5. Protocol Contents 
 
1. 
PROTOCOL FULL TITLE ...........................................................................................................................1 
2. 
STUDY SYNOPSIS .....................................................................................................................................2 
3. 
REVISION HISTORY ..................................................................................................................................4 
4. 
GLOSSARY OF TERMS (OPTIONAL) .......................................................................................................4 
5. 
PROTOCOL CONTENTS ...........................................................................................................................5 
6. 
BACKGROUND & RATIONALE ................................................................................................................7 
7. 
TRIAL OBJECTIVES AND DESIGN ..........................................................................................................8 
7.1 
TRIAL OBJECTIVES .................................................................................................................................8 
Primary endpoints........................................................................................................................................8 
Secondary endpoints ...................................................................................................................................8 
7.2 
TRIAL DESIGN ........................................................................................................................................9 
7.3 
TRIAL FLOWCHART .................................................................................................................................9 
8. 
TRIAL INTERVENTION ..............................................................................................................................9 
8.1 
THERAPY/INTERVENTION DETAILS ...........................................................................................................9 
8.2 
FREQUENCY AND DURATION OF INTERVENTION ...................................................................................... 10 
8.3 
INTERVENTION RECORDS ..................................................................................................................... 11 
8.4 
SUBJECT COMPLIANCE. ....................................................................................................................... 11 
8.5 
STUDY ADHERENCE ............................................................................................................................. 11 
8.6 
5.5 CONCOMITANT MEDICATION ........................................................................................................... 11 
9. 
RESEARCH ENVIRONMENT .................................................................................................................. 11 
10. 
SELECTION AND WITHDRAWAL OF SUBJECTS ............................................................................ 12 
10.1 
INCLUSION CRITERIA ........................................................................................................................ 12 
10.2 
EXCLUSION CRITERIA ....................................................................................................................... 12 
10.3 
SELECTION OF PARTICIPANTS ........................................................................................................... 13 
10.4 
RANDOMISATION PROCEDURE / CODE BREAK ................................................................................... 13 
10.5 
WITHDRAWAL OF SUBJECTS ............................................................................................................. 13 
10.6 
EXPECTED DURATION OF TRIAL. ....................................................................................................... 14 
11. 
TRIAL PROCEDURES ......................................................................................................................... 14 
11.1 
BY VISIT .......................................................................................................................................... 14 
11.2 
LABORATORY TESTS ........................................................................................................................ 14 
12. 
ASSESSMENT OF EFFICACY ............................................................................................................ 14 
12.1 
PRIMARY EFFICACY PARAMETERS .................................................................................................... 14 
12.2 
SECONDARY EFFICACY PARAMETERS ............................................................................................... 14 
12.3 
PROCEDURES FOR ASSESSING EFFICACY PARAMETERS .................................................................... 15 
13. 
ASSESSMENT OF SAFETY ................................................................................................................ 15 
13.1 
SPECIFICATION, TIMING AND RECORDING OF SAFETY PARAMETERS. .................................................. 15 
13.2 
PROCEDURES FOR RECORDING AND REPORTING ADVERSE EVENTS .................................................. 16 
13.2.1 
Adverse events that do not require reporting ............................................................................. 16 
13.3 
STOPPING RULES ............................................................................................................................ 16 

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14. 
STATISTICS ......................................................................................................................................... 17 
14.1 
SAMPLE SIZE ................................................................................................................................... 17 
14.2 
RANDOMISATION .............................................................................................................................. 17 
14.3 
ANALYSIS ........................................................................................................................................ 17 
15. 
TRIAL STEERING COMMITTEE ......................................................................................................... 18 
16. 
DATA MONITORING COMMITTEE ..................................................................................................... 18 
17. 
DIRECT ACCESS TO SOURCE DATA AND DOCUMENTS .............................................................. 18 
18. 
ETHICS & REGULATORY APPROVALS ........................................................................................... 18 
19. 
QUALITY ASSURANCE ...................................................................................................................... 18 
20. 
DATA HANDLING ................................................................................................................................ 19 
21. 
DATA MANAGEMENT ......................................................................................................................... 19 
22. 
PUBLICATION POLICY ....................................................................................................................... 19 
23. 
INSURANCE / INDEMNITY .................................................................................................................. 19 
24. 
FINANCIAL ASPECTS ........................................................................................................................ 19 
25. 
SIGNATURES ...................................................................................................................................... 19 
26. 
REFERENCES ..................................................................................................................................... 20 
27. 
APPENDICES ....................................................................................................................................... 21 
 

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6. Background & Rationale 
Recent reviews highlighted that depression complicates around 10% of pregnancies 7 and that 
untreated or incompletely treated depression is associated with adverse effects for mother and 
unborn child, including maternal suicide, prematurity and childhood emotional problems.7,8  
Antidepressants are indicated for the treatment of moderate to severe depression in pregnancy, 
when psychotherapy alone is unlikely to result in substantive improvements.9 Unfortunately, 
antidepressants are associated with small increased risks of adverse neonatal and obstetric 
outcomes, including congenital cardiac abnormalities, poor neonatal adaptation and preterm birth.7  
The safety evidence is  largely observational, and it is difficult to disentangle the effects of 
depression, medication and associated lifestyle factors.7  
When considering antidepressant use in pregnancy, women and clinicians have to weigh up the 
possible risks of ongoing depression versus antidepressant use, in the face of great scientific 
uncertainty.  These complex decisions are often finely balanced, and need to be guided not only by 
the rapidly changing scientific evidence, but also by the woman’s values, preferences and the 
extent to which she wants to be involved in the treatment decision.9 Women experience high rates 
of conflict and uncertainty in relation to antidepressant use in pregnancy, and this is not addressed 
by usual clinical care - including expert consultation and standard information resources.10 Recent 
studies identified key barriers to decision making in this context- including lack of information, 
difficulty in weighing up risks and benefits and unhelpful external influences10- but also women’s 
desire for greater involvement in the decision making process.11  
Patient decision aids aim to improve shared decision-making for complex health decisions such as 
this one, which involve weighing up uncertain benefits and harms. 12 A 2014 Cochrane Systematic 
Review of 115 decision aids for a variety of screening and treatment decisions found that their use 
improved patients’ knowledge and risk perception, helped patients to make informed value-based 
choices and improved patient-clinician communication,12  but to our knowledge there are no 
evaluated PDAs for antidepressant use in pregnancy.  
To address this gap, we have developed an electronic PDA for antidepressant use in pregnancy.  
The PDA was developed by leading international experts in Canada, with expertise in decision 
aids, perinatal psychiatry and psychopharmacology (Louise Howard, PI, was on the advisory group 
and Simone Vigod, co-investigator, led the development). The PDA’s content and layout were 
informed by: (1) The International Patient Decision Aids Standard (IPDAS) collaboration guidelines 
13; (2) Published systematic reviews of evidence related to the benefits and harms of 
antidepressant treatment in pregnancy (several conducted by team members) 14-17; and (3) 
Evidence related to the decisional needs of patients faced with this complex decision.10,11 The 
prototype was developed by the healthcare technology company, QoC Health 
(http://qochealth.com/). It was revised on the basis of feedback from a multidisciplinary 
international steering committee, and the findings of an open-label acceptability trial in the target 
population. The PDA’s content and format are described in section 8.1 below (see Appendix for 
further details).  
The proposed study is a pilot RCT of this PDA based in London with nationwide recruitment, to be 
conducted in parallel with a pilot RCT in Toronto. The latter is already underway, following an 
open-label trial (N=13 patients); which found that the PDA was acceptable to patients and that its 
use was associated with a 52% reduction in the Decisional Conflict Scale score. The findings from 
the pilot RCTs in London and Toronto will inform a future international definitive RCT. 
 
 

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7. Trial Objectives and Design  
7.1 
Trial Objectives 
The primary objective of this pilot study is the feasibility of conducting a large RCT to evaluate 
the efficacy of the PDA. This comprises 1) feasibility (how well the trial protocol can be 
implemented), (2) acceptability (usability and tolerability of the intervention and of randomisation 
including patient and provider views) and (3) adherence (the degree to which the trial protocol is 
followed). Secondary outcomes will include preliminary effect sizes of the PDA to inform sample 
size calculations for the future RCT.  
Primary endpoints 
 
(A) Feasibility: Measured in terms of (1) eligibility (e.g. proportion of patients eligible); (2) 
recruitment (e.g. rates overall and by recruitment strategy, non-participation reasons); and (3) 
timing (e.g. enrolment to first log-in to the PDA).  
 
(B) Acceptability: This will measured by: (1) The Decision Support Tool Acceptability 
Questionnaire (for participants randomized to receive the PDA intervention only). (2) Sudy website 
usage (including number of women who complete the PDA; number of electronic logins & length of 
time required to complete the PDA; number of participants who use the PDA summary sheet with 
their provider); (3) The Provider Perspective Survey  
 
(C) Adherence with trial protocol: This will be measured by: (1) number of participants who 
follow-up with their clinician within the intended active study phase (i.e. 4 weeks post-
randomization); and (2) The rate of follow-up data collection at each time point.   
 
Secondary endpoints 
 
Secondary outcomes will inform the sample size required for a future RCT of the effectiveness of 
the tool. Decisional conflict will be the primary outcome for the future RCT, as has been the case in 
previous PDA studies, 18,19 measured using the Decisional Conflict Scale.20 Secondary outcomes 
measures for the future RCT are listed below. 
 
A. Decisional Conflict Scale (DCS)20  The purpose of this scale is to measure a person’s 
perception of difficulty in making a decision including: (1) uncertainty in choosing between 
options, (2) modifiable factors contributing to uncertainty such as feeling uninformed, 
unclear about personal values, and unsupported, and (3) quality of the choice selected, 
which is defined as informed and consistent with personal values, and with which a person 
expresses personal satisfaction20. The DCS consists of 16 items (ranging from 1 to 5, with 5 
being high decisional conflict). Scores of 25 or greater are associated with those who delay 
decisions. Test-retest and internal consistency coefficients exceed 0.78.   
B. Knowledge Questionnaire:2  Knowledge of depression treatment options will be assessed 
using a knowledge questionnaire that includes items regarding the effectiveness of various 
treatment options, as well as known possible adverse effects. Effectiveness estimates will 
be presented in the form of a continuous scale from 0 to 100%. Content knowledge items 
will be presented as ‘true’ or false’.  This tool is a modified version of a tool previously 
created and validated by a member of the Canadian team in other PDA evaluations. 
C. Participant-Provider Clinical Interaction: We will audiotape the first patient-provider visit 
following the intervention if patient and clinician agree.  Audiotapes will be transcribed 
verbatim and analyzed using (i) framework qualitative analysis6 and (ii) the OPTIONS scale; 
a 12-item observer-rated validated and widely used scale for measuring shared decision-

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making.5,21 Clinicians will have the opportunity to review the PDA and the research protocol 
prior to the start of the study and can opt out of the audiotaping at any time.    
D. Edinburgh Postnatal Depression Scale (EPDS):3. We will measure depressive symptoms 
using the EPDS, a self-report depression screening measure that has been validated for 
use in pregnancyEPDS scores > 12 are predictive of a diagnosis of major depressive 
disorder.    
E. Spielburg State-Trait Anxiety Inventory (STAI):22 We will measure anxious symptoms using 
the STAI, a self-report anxiety screening measure that has shown good discriminately 
validity in perinatal populations.  STAI scores > 48 are predictive of having an anxiety 
disorder diagnosis, 
7.2 
Trial Design  
A pilot parallel group, investigator-blind randomised controlled trial. 
7.3 
Trial Flowchart 
 
  Trial flowchart 
Study Variable 
Sampl
e 
Measure 
Prior to 
enrolment 
Baseline 
Clinic 
Visit 
4 
weeks  
LT F/U5 
Eligibility 
All 
subjec
ts 
Eligibility assessment 
X 
 
 
 
 
Participation 
rate 
Written consent (obtained 
in person, online or by 
post). 
X 
 
 
 
 
Demographics 
Participant CharacteristicsCo 
 
X 
 
 
 
Mental Health  
MINICo, 1 
 
X 
 
 
 
EPDSE, 2 & STAI E, 3 
 
X 
 
X 
X 
Decisional 
Conflict 
Decisional Conflict ScaleE 
 
X 
 
X 
 
Knowledge 
Knowledge QuestionnaireE 
 
X 
 
X 
 
Adherence 
Website Use & Chart 
ReviewF 
 
 
 
X 
X 
Patient-
Provider  
Audiotaped Clinic VisitE; 
analysed using qualitative 
Framework Analysis and 
the OPTIONS scale4 
 
 
X 
 
 
Decision 
Health Service 
QuestionnaireCo 
 
X 
 
X 
X 
Participant 
View 
PDA 
only 
Acceptability 
QuestionnaireF 
 
 
 
X 
 
Provider Views 
Provid
ers 
Provider Perspective 
SurveyF 
 
 
 
 
X* 
Legend: FFeasibility; EEfficacy; CoCovariate; 1Mini Neuropsychiatric Interview; 2Edinburgh Postnatal Depression Scale; 
3State-Trait Anxiety Inventory; 4Observing Patient Involvement in Shared Decision-making;  5LT f/u = Long Term 
Follow-Up: At 12 weeks postpartum (for women enrolled while pregnant) or 6 months after baseline assessment (for 
women enrolled while planning a pregnancy); *Collected only after all other subject data collection is complete 
 
 
8. Trial Intervention 
8.1 
 Therapy/Intervention Details 
Experimental and control group interventions will be delivered online. Women randomized to the 
intervention arm will access the electronic PDA described below. Women randomized to the 

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control arm will login to the study website and receive a printable PDF containing references to 
standard published information on depression and antidepressant use in pregnancy (see Appendix 
for details). This ensures women have access to accurate information on the benefits and risks of 
antidepressant medication in pregnancy (even though they will not receive the PDA).  Also, this will 
allow us to evaluate the efficacy of the PDA (plus clinical care) compared to available information 
and resources (plus clinical care) in the future RCT. All participants will receive close clinical 
monitoring, as per standard care. 
The interactive, electronic PDA has 3 main sections: (1) Evidence-based information about 
depression in pregnancy and each treatment option and procedure; (2) evidence-based 
information on the risks and benefits of both untreated depression and antidepressant treatment, 
integrated with a series of exercises to help women determine which risks and benefits are most 
important to them. This section also includes exercises to help women consider how their 
relationships with others (e.g. partners, friends, and providers) affects the decision-making 
process; and (3) a summary section that outlines the information reviewed and which benefits and 
risks they deemed most important. Participants can choose the amount of complex information that 
want to access and read (by clicking on ‘further information’ links). At the end of the module, they 
will see a summary PDF which they can print and use in clinical follow-up. They will also receive a 
printable PDF containing references to standard published information and resources on 
depression and antidepressant use in pregnancy (see Appendix).  
Women will have access to the study website until their final follow-up or until the end of the main 
study period (at least three months after the final woman is randomised).. They can access it 
multiple times at a time and place that suits them, alone or with others (e.g. family, friends). For 
those who cannot access the study website on a personal computer, we will provide access in a 
private area in a clinical setting. 
8.2 
Frequency and duration of intervention 
Baseline data will be collected by the researcher after consent has been obtained.  
Consent will be obtained in person where possible (and mainly for participants recruited in 
London). For participants who are not seen in person, a copy of the Patient Information Sheet and 
the consent form will be made available online (on the study website) and also by post / email (if 
potential participants request this). Women interested in participating will be asked to provide their 
contact details (by online submission, email or phone) - and a member of the study team will phone 
them to answer any queries about the study and go through the consent form. Following this, 
women who want to participate will be asked to complete the consent form, including their name 
and date, and send it to the research team (by online submission, email or post).  For consent 
forms sent by participants to the study team online or by email, we will not require a signature and 
participants will be asked to give their initials to indicate their consent. 
Baseline data will be collected in person or over the phone (or on skype, as per patient 
preference).  After completion of baseline measures, participants will be asked to access the study 
website and review the website information (i.e. PDA or control condition) prior to the next 
encounter with their clinical provider, which should be scheduled as soon as possible (and within 4 
weeks of randomisation) because of the urgency of deciding on treatment for depression in 
pregnancy. A 4-week time period in which to review the PDA and follow-up with the clinical 
provider was chosen to allow women adequate time to review the PDA (perhaps log-in multiple 
times if desired) and make treatment decisions with their clinical provider. Participants will have 
access to the PDA until their final follow-up or until the end of the main study period. 
The researcher will arrange to audio-tape the first follow-up appointment after randomisation, to 
assess the impact of the PDA on participant-provider clinical interaction (if clinicians and patients 

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agree to this and if it is feasible for the researcher to travel to the clinical site with an audio-
recorder).   
 
The researcher will collect follow-up outcome measures at: (1) 4 weeks post-randomization; and 
(2) either 12 weeks postpartum (if the participant enrolled while pregnant) or 6 months post-
randomization (if the participant enrolled while planning a pregnancy). This will be done in person 
or over the phone (or on skype, as per patient preference). Providers whose patients were enrolled 
in the study will complete a Provider Perspective Survey. The overall time spent in the study will be 
up to one year. 
 
8.3 
Intervention records 
Access to the study website will be recorded using the web-system log. The first follow-up 
appointment after randomisation will be audiotaped (if feasible and if the doctor and patient agree 
to this) to assess the impact of the PDA on participant-provider clinical interaction.   
8.4 
Subject Compliance. 
Participant compliance will be determined by measuring (a) access to the study’s electronic 
website, using the web-system log; (b) proportion of patients who attend a follow-up appointment 
within 4 weeks of randomisation; (c) proportion of participants randomised to the PDA arm who 
bring the PDA’s summary PDF to their follow-up appointment 
8.5 
Study adherence 
We will use several post-recruitment retention strategies to retain participants in this study and 
optimize follow-up data collection rates. We will provide travel expenses as required and both 
baseline and follow-up data can be collected over the phone or on skype. Women will receive £20 
following completion of the baseline interview and each of the follow-up interviews, in appreciation 
of their time. After completion of the first follow-up questionnaire and audio-taped clinic visit, 
women will be contacted by telephone and/or email to remind them about their second follow-up 
assessment. In addition, women without computer and/or internet access at home will be provided 
with access to a laptop which can be used at a clinical site to complete the online component of the 
study intervention, if this is feasible to arrange.  
 
Adherence (i.e. access to the study website and rates of clinical follow-up within 4 weeks) will be 
measured as in section 8.4 above. 
 
8.6 
5.5 Concomitant Medication 
This pilot will recruit women who are considering starting or continuing an antidepressant during 
pregnancy. Participants may be prescribed one or more medications during the trial period, 
including an antidepressant, and any such prescribing is permitted concurrently with the 
intervention. All medications prescribed will be recorded at baseline and each follow-up point. 
9. Research environment 
This pilot RCT will be based in London, recruiting from local services (see below) and nationally via 
self-referral (e.g. through online advertising), and will be conducted in parallel with a pilot RCT in 
Toronto, Canada. 
 
The pilot will recruit women in London who are under the care of one or more of the following 
services: (a) GP practices in London; (b) mental health services in South London and Maudsley 
NHS Foundation Trust, including specialist perinatal psychiatric services in King's College Hospital, 

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St Thomas's Hospital and community clinics in Lewisham and Croydon and (c) maternity services 
in King’s College Hospital, Guy’s & St Thomas’s hospital and Croydon University Hospital. National 
recruitment will occur via online advertising to potential participants and information sent to 
relevant clinicians. The clinicians outside London will not recruit women into the study but will be 
able to provide information about the study (e.g. details of the study website) to potentially eligible 
women who will then be able to self-refer into the study or find out more about the study using the 
contact sheet on the website. Please see Appendix for details. 
10. Selection and Withdrawal of Subjects  
10.1 Inclusion Criteria  
Women are eligible to participate if they meet all of the following inclusion criteria:  
• 
Aged 18 or over 
• 
Are planning a pregnancy or are <30 weeks pregnant at enrolment 
• 
Have been offered to start or continue an antidepressant as treatment for depression by 
their clinician  
• 
Have moderate-to-high decisional conflict (score of >25 on the Decisional Conflict Scale).  
• 
Have given written informed consent to participate.  
 
10.2 Exclusion Criteria  
Women will be excluded from the study if they meet any of the following exclusion criteria:  
• 
Are aged <18 
• 
Have had alcohol or drug abuse or dependence in the previous 12 months  
• 
Have active suicidal ideation or psychosis 
• 
Are incapable of consenting to participation 
• 
Have any major obstetric complications or foetal cardiac anomaly in the current or in a past 
pregnancy 
• 
Are visually impaired 
• 
Do not have sufficient English language proficiency to use the PDA 
When we discuss antidepressants in this decision aid, we are talking about all of the following 
antidepressant medications: 
 
Generic name (US brand name) 
 
UK brand name 
• 
Citalopram (Celexa™) 
 
 
Cipramil 
• 
Escitalopram (Cipralex™) 
 
 
Cipralex 
• 
Fluoxetine (Prozac™)  
 
 
Prozac, Olena 
• 
Fluvoxamine (Luvox™) 
 
 
Faverin 
• 
Paroxetine (Paxil™)  
 
 
Seroxat 
• 
Sertraline (Zoloft™) 
 
 
 
Lustral 
• 
Venlafaxine (Effexor™) 
 
 
Efexor 
• 
Duloxetine (Cymbalta™) 
 
 
Cymbalta 

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• 
Desvenlafaxine (Pristiq™) 
 
 
Not used in UK 
Only women who are taking or have been recommended to start taking an antidepressant listed 
above are eligible to participate in this study. This decision aid does not focus on antidepressant 
medications such as Mirtazapine (RemeronTM) or Bupropion (Wellbutrin TM), nor other, less 
commonly prescribed medications for depression such as tricyclic antidepressants or monoamine 
oxidase inhibitors. 
10.3 Selection of Participants  
The study will aim to recruit 50 women over a one year period, and to establish the most effective 
recruitment strategies for use in a future definitive RCT. We will recruit in London from: (a) GP 
practices; (b) mental health services in South London and Maudsley NHS Foundation Trust, 
including specialist perinatal psychiatric services in King's College Hospital, St Thomas's Hospital 
and community clinics in Lewisham and Croydon and (c) maternity services in King’s College 
Hospital, Guy’s & St Thomas’s hospital and Croydon University Hospital. We will identify potential 
participants using a variety of methods, including: (a) asking clinicians to identify and refer 
potentially eligible patients who are interested in taking part; (b) using the SLAM ‘Consent for 
Contact’ programme and (c) direct advertising to patients in clinical areas and via websites and 
social media. We will recruit nationally through online advertising to potential participants. For 
example, through the website NetMums, which offers support and information on pregnancy and 
parenting, including a section on perinatal depression, and has collaborated with research on 
antenatal depression in the recent past. Organisations which provide information and support 
about pregnancy (e.g. NCT, Tommy’s Baby Charity and PANDAS [Pre and Postnatal Depression 
Advice and Support]) will also be approached to promote the study on social media (e.g. Twitter 
and Facebook). All online advertising will link to a webpage about the study (see Appendix) hosted 
on the King’s College London website, which will provide women with more details about the study 
including the participant information sheet and consent form, contact details for the research team, 
and a form to enable women to provide the researchers with their contact details. In addition, we 
will send information about the study to relevant clinicians nationally. The clinicians outside London 
will not recruit women into the study but will provide information about the study (e.g. details of the 
study website) to potentially eligible women who will then be able to self-refer into the study and 
find out more about the study using the contact sheet on the website. 
Multiple methods of recruitment are being used for this study because it is a pilot trial and aiming to 
assess the feasibility of a number of alternatives for recruitment that could be used in a larger trial 
of the Patient Decision Aid. In all cases, we will only enrol patients after their clinical team has 
been contacted, to establish eligibility and inform them of the woman’s planned participation in the 
trial. We will obtain consent (written or verbal) from women to contact their clinical team.  
 
10.4 Randomisation Procedure / Code Break 
Participants will be randomized to the PDA or control group using a computer-generated random 
allocation sequence. After consent has been obtained and baseline assessments have been 
administered, the researcher will provide the participant with a card or email with the website 
address for the study and the participant’s study ID number, which will serve as their website login. 
At login, the participant ID will be matched automatically within the program to the predetermined, 
concealed, allocation sequence and the participant will receive the allocated intervention. 
Participants will be randomized 1:1 ratio with stratification by whether they are recruited from 
primary care or psychiatric settings. 
10.5 Withdrawal of Subjects  
Participants have the right to withdraw from the study at any time for any reason.  The investigator 
also has the right to withdraw patients from the study in the event of inter-current illness, AEs, 
SAE’s, protocol violations, administrative reasons or other reasons (see below for details).  It is 

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understood by all concerned that an excessive rate of withdrawals can render the study 
uninterpretable; therefore, unnecessary withdrawal of patients will be avoided.  Should a patient 
decide to withdraw from the study, all efforts will be made to report the reason for withdrawal as 
thoroughly as possible.  Should a patient withdraw from the study, efforts will be made to continue 
to obtain follow-up data, with the permission of the patient. 
Safety will be assessed at all follow-up time points and be routinely reviewed by the PI.  Adverse 
events will be recorded and serious adverse events immediately reported (within 24 hours by 
telephone or fax) to the CI (Louise Howard) for consideration of further action. Protocols will be 
developed regarding specific criteria for participant withdrawal during the active study phase that 
will include active suicidal ideation, psychosis and acute pregnancy complications that might 
change the considerations required for treatment decisions. If withdrawal criteria are met, the 
participant will be withdrawn from the study intervention and followed by her physician as per usual 
care. We will attempt to collect follow-up data, with the patient’s permission. Participants who 
terminate early will be part of intention to treat analysis. 
 
10.6 Expected Duration of Trial. 
The study duration will be from the patient’s first baseline assessment to the last follow-up 
assessment: either 12 weeks postpartum (if the participant enrolled while pregnant) or 6 months 
post-randomization (if the participant enrolled while planning a pregnancy). So overall, the 
expected duration is 6 to 12 months. 
11.  Trial Procedures  
11.1  By Visit 
 
• 
At pre-enrolment: the researcher will assess eligibility and obtain written informed consent 
from those willing to participate (using the procedure described in section 8.2).  
• 
At the baseline assessment, the researcher will administer the relevant study 
questionnaires to the patient (see section 7.3); provide the participant with a card or email 
with the study website address and the participant’s study ID number (which will serve as 
their website login) and ask the patient to book a follow-up appointment with their clinician 
within 4 weeks 
• 
The first clinical follow-up appointment post randomization will be  audiotaped if this is 
feasible and the patient and doctor agree to this 
• 
At the 4-week and long-term research follow up appointments, the researcher will 
administer the relevant study questionnaire to the patient (see section 7.3) 
11.2 Laboratory Tests 
No laboratory measurements are required. 
12. Assessment of Efficacy  
12.1 Primary Efficacy Parameters 
 
 
For this pilot RCT, the primary efficacy outcome is the feasibility of the study protocol, as detailed 
in section 7.1. This is because the primary aim of this pilot is to assess the feasibility of a future 
definitive RCT of the PDA’s efficacy. 
12.2 Secondary Efficacy Parameters 

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Secondary outcomes will inform the sample size required for a future RCT of the effectiveness of 
the tool: Decisional conflict will be the primary outcome for the future RCT, as has been the case in 
previous PDA studies18,19. Additional outcome measures will include knowledge comprehension, 
the impact of the PDA on the participant-provider clinical interaction and psychiatric symptoms at 
follow-up. See section 7.1 for details. 
 
12.3 Procedures for Assessing Efficacy Parameters 
Efficacy parameters will be measured using questionnaires and analysis of an audiotaped clinical 
follow-up appointment. See section 7.1 and 7.3 for details. The table detailing the relevant 
measures is copied here for ease of reference: 
  Trial flowchart 
Study Variable 
Sampl
e 
Measure 
Prior to 
enrolment 
Baseline 
Clinic 
Visit 
4 
weeks  
LT F/U5 
Eligibility 
All 
subjec
ts 
Eligibility assessment 
X 
 
 
 
 
Participation 
rate 
Written consent (obtained 
in person, online or by 
post). 
X 
 
 
 
 
Demographics 
Participant CharacteristicsCo 
 
X 
 
 
 
Mental Health  
MINICo, 1 
 
X 
 
 
 
EPDSE, 2 & STAI E, 3 
 
X 
 
X 
X 
Decisional 
Conflict 
Decisional Conflict ScaleE 
 
X 
 
X 
 
Knowledge 
Knowledge QuestionnaireE 
 
X 
 
X 
 
Adherence 
Website Use & Chart 
ReviewF 
 
 
 
X 
X 
Patient-
Provider  
Audiotaped Clinic VisitE; 
analysed using qualitative 
Framework Analysis and 
the OPTIONS scale4 
 
 
X 
 
 
Decision 
Health Service 
QuestionnaireCo 
 
X 
 
X 
X 
Participant 
View 
PDA 
only 
Acceptability 
QuestionnaireF 
 
 
 
X 
 
Provider Views 
Provid
ers 
Provider Perspective 
SurveyF 
 
 
 
 
X* 
Legend: FFeasibility; EEfficacy; CoCovariate; 1Mini Neuropsychiatric Interview; 2Edinburgh Postnatal Depression Scale; 
3State-Trait Anxiety Inventory; 4Observing Patient Involvement in Shared Decision-making;  5LT f/u = Long Term 
Follow-Up: At 12 weeks postpartum (for women enrolled while pregnant) or 6 months after baseline assessment (for 
women enrolled while planning a pregnancy); *Collected only after all other subject data collection is complete 
 
13. Assessment of Safety  
13.1 Specification, Timing and Recording of Safety Parameters.  
The intervention in this pilot RCT (the use of an electronic patient decision aid) is a low risk 
procedure. A recent Cochrane review of 115 RCTs of PDAs for a range of clinical decisions did not 
identify any harms from the use of PDAs to the patient, the decision-making process or the patient-
provider interaction.12 Nonetheless, safety will be assessed by the researcher at each assessment 
point (baseline, 4-week follow-up, long-term follow-up). Safety will also be assessed by the 
clinician in the course of routine clinical care, which often involves intensive follow-up in this 

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population. Protocols will be developed regarding specific criteria for participant withdrawal during 
the active study phase that will include active suicidal ideation, psychosis and acute pregnancy 
complications that might change the considerations required for treatment decisions. If withdrawal 
criteria are met, the participant will be withdrawn from the study intervention and followed by her 
physician.   
 
13.2 Procedures for Recording and Reporting Adverse Events 
Adverse Event (AE): Any untoward medical occurrence in a subject to whom a therapy has been 
administered including occurrences which are not necessarily caused by or related to that therapy. 
Adverse Reaction (AR): Any untoward and unintended response in a subject to a therapy which is 
related to any duration of therapy administered to that subject. 
Unexpected Adverse Reaction (UAR): An adverse reaction the nature and severity of which is not 
consistent with the information known about the therapy in question in the view of the investigator 
Serious adverse Event (SAE), Serious Adverse Reaction (SAR) or Unexpected Serious Adverse 
Reaction (USAR): Any adverse event, adverse  reaction or unexpected adverse reaction, respectively, 
that 
• 
Results in death; 
• 
Is life-threatening; 
• 
Required hospitalisation or prolongation of  existing hospitalisation; 
• 
Results in persistent or significant disability or incapacity; 
• 
Consists of a congenital anomaly or birth defect. 
Reporting Responsibilities 
All SARs and SUSARs (excepting those specified in this protocol as not requiring reporting) will be 
reported immediately by the Chief Investigator to the R&D office 
 
13.2.1 Adverse events that do not require reporting 
 
No potential related adverse events are expected in this pilot trial. As part of the study 
interventions, the woman will access information on depression and antidepressant use in 
pregnancy. This will be done in the context of a health professional having recommended an 
antidepressant in pregnancy, so any queries or concerns arising from accessing this information 
via the study intervention would be addressed in the course of usual clinical care.  If there are any 
concerns about a woman’s mental health or risk during the course of the study (e.g. emotional 
distress, suicidal ideas), the researcher will alert the CI (Louise Howard) and will arrange for the 
woman to have increased support from her clinical team. 
13.3 Stopping Rules 
 
The trial may be prematurely discontinued by the Sponsor or Chief Investigator on the basis of 
new safety information or for other reasons given by the regulatory authority or ethics committee 
concerned (for example if important new risk information emerges about antidepressant use in 
pregnancy during the study period which is not incorporated into the PDA). 
The trial may also be prematurely discontinued due to lack of recruitment. If the study is 
prematurely discontinued, active participants will be informed and no further participant data will 
be collected. 

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14. Statistics 
 
 
 
14.1 Sample Size 
We estimated that a minimum sample size of 40 (20 per intervention arm) was required for this 
pilot RCT based on (a) a review by Hertzog, which suggested a range of 20-40 participants for 
assessing the acceptability of an intervention23; and  (b) pilot data for the primary outcome that we 
intend to use in a future efficacy RCT- the Decisional Conflict Scale (DCS). Among women with 
mean DCS score=30 (moderate-high) and SD 14.8 (based on pilot data), a total sample size of 40 
participants would allow the detection of a 13-point difference in DCS scores (clinically significant) 
between intervention & control groups with probability (power) 0.8 (alpha=0.05). We aim is to 
recruit at least 25 participants to each intervention group, allowing for 20% loss to follow-up for a 
minimum of 20 per group retained in the study.  
In the hospitals affiliated with King’s Health Partners (King’s College Hospital and Guy’s and St 
Thomas’s Hospitals) there are approximately 12,000 deliveries per year.  Based on UK national 
data and Toronto pilot work, we assume that (a) at least 3% of pregnant women would be 
considered for an antidepressant (based on national UK data),24 and (b) 40% of these women 
would be eligible for this study,10 and (c) 60% of those eligible would agree to participate10. 
Therefore, if all potentially eligible women were identified and referred to the study team, we could 
reach our recruitment target of 50 women over a 7-month period in our study setting. In practice, 
we have discovered that the rate of identification and referral of potentially eligible women into the 
study is extremely low (over a 5-month period seven potentially eligible women were referred to the 
study, of whom two were eligible and one participated in the study). We are therefore expanding to 
include national recruitment via online advertising and information sent to relevant clinicians.  
14.2 Randomisation 
Participants will be randomized 1:1 ratio with stratification by whether they are currently pregnant 
or planning pregnancy.  
 
Researchers will be blind to group allocation at all data collection time points. PDA acceptability 
data will be collected by a different researcher in order to maintain blinding. Participants cannot be 
blinded as to which intervention they received, due to the nature of the intervention, but they will be 
blinded to study hypotheses. Providers may or may not become aware of the participant’s 
allocation depending on whether or not participants discuss their use of the PDA with them. 
However, providers will not collect outcome data, minimizing risk for measurement bias due to lack 
of blinding.   
 
14.3 Analysis 
 
 
(1) Statistical analysis: Means will be calculated to determine feasibility and compliance estimates 
for recruitment rate for each strategy, rates of nonparticipation, completion rate of the PDA, follow-
up rates at the various intervals, and so on. We will calculate the acceptability of the intervention 
using the Likert-type scale responses from the participant and provider questionnaires, and will 
collate additional comments made by participants or providers for consideration of modifications to 

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the content, layout or technical capacity of the PDA.  To compare decisional conflict between 
women receiving the PDA to women receiving the comparison condition at 4 week follow-up we 
will use the intention-to-treat principle. Missing data points will be excluded from the analysis, and 
individuals with less than 2 DCS measurements will be treated as lost to follow-up. An on-
treatment analysis will also be performed as a sensitivity analysis (for best possible performance of 
the PDA). Means of the DCS scores of the experimental and comparison groups at the primary 
endpoint will be compared using a one-way ANCOVA model, where the covariate will be baseline 
DCS score. Results will be stratified by centre. This effect size will be used to generate the sample 
size needed for the future RCT 
(2) Qualitative analysis: after transcribing the audiotaped follow-up appointment, data will be 
analysed using framework analysis (which entails the 5 key steps of familiarisation, coding, 
developing an analytical framework, indexing and data interpretation).6 The interview will also be 
analysed using the observer-rated OPTION Scale for shared decision-making.5 
 
15. Trial Steering Committee  
A Trial Steering Committee will not be used for this small, low-risk pilot RCT. 
16. Data Monitoring Committee  
Because of the low risk nature of this intervention, an independent Data Safety Monitoring Board 
will not be developed. Safety will be assessed at all follow-up time points and be routinely reviewed 
by the PI.  Adverse events will be recorded and serious adverse events immediately reported 
(within 24 hours by telephone or fax) to the CI (Louise Howard) for consideration of further action. 
17. Direct Access to Source Data and Documents 
The Investigator(s) will permit trial-related monitoring, audits and REC review  by providing the Sponsor(s), 
and REC direct access to source data and other documents (eg patients’ case sheets). 
18. Ethics & Regulatory Approvals 
The trial will be conducted in compliance with the principles of the Declaration of Helsinki (1996), the 
principles of GCP and in accordance with all applicable regulatory requirements including but not limited to 
the Research Governance Framework and the Mental Capacity Act 2005. 
This protocol and related documents will be submitted for review to London - Queen Square Research 
Ethics Committee (REC) 
The Chief Investigator will submit a final report at conclusion of the trial to the funder, the REC and the 
Sponsor  
19. Quality Assurance 
 
Monitoring of this trial will be to ensure compliance with Good Clinical Practice and scientific 
integrity will be managed by the study team. A committee consisting of the UK and Canadian PIs 
and study co-investigators and the research assistants will hold teleconferences as necessary 
(every 2 months) to discuss study progress, including participant recruitment, and unexpected 
issues.  The lead sponsor, King's College London, will take primary responsibility for ensuring that 
the design of the trial meets appropriate standards and that arrangements are in place to ensure 
appropriate conduct and reporting. 

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20. Data Handling  
The Chief Investigator will act as custodian for the trial data. The following guidelines will be strictly adhered 
to: 
• 
Patient data will be anonymised 
• 
All anonymised data will be stored on a password protected computer. 
• 
All trial data will be stored in line with the Data Protection Act. 
• 
and archived in line with Sponsor requirements 
21. Data Management 
Two electronic databases will be created using Excel spreadsheets (a) a database with identifying 
data (name, contact details), which will be password-protected and (b) a  separate anonymised  
database, using study IDs only, which will contain study-specific outcomes (e.g. details on 
eligibility, consent, reasons for non-participation and findings from the baseline and follow-up 
assessmsents). Data will be handled in line with the Data Protection Act as detailed in section 20.  
22. Publication Policy  
 
It is intended that the results of the study will be reported and disseminated at international 
conferences and in peer-reviewed scientific journals. 
23. Insurance / Indemnity  
King's College London provides cover under its No Fault Compensation Insurance, which provides for 
payment of damages or compensation in respect of any claim made by a research subject for bodily injury 
arising out of participation in a clinical trial or healthy volunteer study (with certain restrictions). 
24. Financial Aspects  
 
Funding to conduct the trial is provided by an NIHR Research Professorship (£1,499,280 over a 5-year 
period from 2013-2018) 
25. Signatures 
 
 
______________________________________ 
_________________________ 
Chief Investigator 
Date 
Print name 
 
 
______________________________________ 
_________________________ 
Statistician (if applicable) 
Date 
Print name 
 
 

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26. References  
 
1. 
O'Connor AM, Bennett CL, Stacey D, et al. Decision aids for people facing health treatment or 
screening decisions. Cochrane Database Syst Rev. 2009(3):119. 
2. 
Metcalfe KA, Poll A, O'Connor A, et al. Development and testing of a decision aid for breast cancer 
prevention for women with a BRCA1 or BRCA2 mutation. Clin Genet. Sep 2007;72(3):208-217. 
3. 
Gibson J, McKenzie-McHarg K, Shakespeare J, Price J, Gray R. A systematic review of studies 
validating the Edinburgh Postnatal Depression Scale in antepartum and postpartum women. Acta Psychiatr 
Scand. May 2009;119(5):350-364. 
4. 
Dennis CL, Coghlan M, Vigod S. Can we identify mothers at-risk for postpartum anxiety in the 
immediate postpartum period using the State-Trait Anxiety Inventory? J Affect Disord. Jun 10 2013. 
5. 
Elwyn G, Edwards A, Wensing M, Hood K, Atwell C, Grol R. Shared decision making: developing the 
OPTION scale for measuring patient involvement. Qual. Saf. Health Care. Apr 2003;12(2):93-99. 
6. 
Gale N, Heath G, Cameron E, Rashid S, Redwood S. Using the framework method for the analysis 
of qualitative data in multi-disciplinary health research. BMC Medical Research Methodology. 
2013;13(1):117. 
7. 
Howard LM, Molyneaux E, Dennis C-L, Rochat T, Stein A, Milgrom J. Non-psychotic mental 
disorders in the perinatal period. The Lancet. 2014;384(9956):1775-1788. 
8. 
Stein A, Pearson RM, Goodman SH, et al. Effects of perinatal mental disorders on the fetus and 
child. The Lancet. 2014;384(9956):1800-1819. 
9. 
NICE. Antenatal and postnatal mental health: clinical management and service guidance. London: 
NICE 2014. 
10. 
Walton GD, Ross LE, Stewart DE, Grigoriadis S, Dennis CL, Vigod S. Decisional conflict among 
women considering antidepressant medication use in pregnancy. Arch Womens Ment Health. Aug 9 2014. 
11. 
Patel SR, Wisner KL. Decision making for depression treatment during pregnancy and the 
postpartum period. Depress Anxiety. Jul 2011;28(7):589-595. 
12. 
Stacey D, Legare F, Col NF, et al. Decision aids for people facing health treatment or screening 
decisions. The Cochrane database of systematic reviews. 2014 2014;1:CD001431. 
13. 
Coulter A, Kryworuchko J, Mullen PD, Ng CJ, Stilwell D, van der Weigden T. Chapter A. Using a 
Systematic Development Process. In: Volk R, Llewellyn-Thomas H, eds. Update of the International Patient 
Decision Aids Standards (IPDAS) Collaborations' Background Document.2012. 
14. 
Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. The impact of maternal depression during 
pregnancy on perinatal outcomes: a systematic review and meta-analysis. J Clin Psychiatry. Apr 
2013;74(4):e321-341. 
15. 
Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. The effect of prenatal antidepressant 
exposure on neonatal adaptation: a systematic review and meta-analysis. J Clin Psychiatry. Apr 
2013;74(4):e309-320. 
16. 
Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. Antidepressant exposure during pregnancy 
and congenital malformations: is there an association? A systematic review and meta-analysis of the best 
evidence. J Clin Psychiatry. Apr 2013;74(4):e293-308. 

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17. 
Ross LE, Grigoriadis S, Mamisashvili L, et al. Selected pregnancy and delivery outcomes after 
exposure to antidepressant medication: a systematic review and meta-analysis. JAMA Psychiatry. Apr 
2013;70(4):436-443. 
18. 
Stacey D, Bennett CL, Barry MJ, et al. Decision aids for people facing health treatment or screening 
decisions. Cochrane Database Syst Rev. 2011(10):CD001431. 
19. 
Vlemmix F, Warendorf JK, Rosman AN, et al. Decision aids to improve informed decision-making in 
pregnancy care: a systematic review. BJOG : an international journal of obstetrics and gynaecology. Feb 
2013;120(3):257-266. 
20. 
O'Connor AM. Validation of a decisional conflict scale. Med Decis Making. Jan-Mar 1995;15(1):25-
30. 
21. 
Scholl I, Koelewijn-van Loon M, Sepucha K, et al. Measurement of shared decision making - a 
review of instruments. Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen. 2011 (Epub 
2011 May 2011;105(4):313-324. 
22. 
Dennis CL, Coghlan M, Vigod S. Can we identify mothers at-risk for postpartum anxiety in the 
immediate postpartum period using the State-Trait Anxiety Inventory? J Affect Disord. Sep 25 
2013;150(3):1217-1220. 
23. 
Hertzog MA. Considerations in determining sample size for pilot studies. Research in nursing & 
health. Apr 2008;31(2):180-191. 
24. 
Petersen I, Gilbert RE, Evans SJW, Man SL, Nazareth I. Pregnancy as a Major Determinant for 
Discontinuation of Antidepressants: An Analysis of Data From The Health Improvement Network. J. Clin. 
Psychiatry. Jul 2011;72(7):979-985. 
 
 
27.  Appendices 
• 
Patient Information Sheet 
• 
Sample Consent Form 
• 
Study Measures 
• 
Study webpage preview 
• 
Clinician email (to ensure that the woman is suitable to participate) 
• 
Login email (participant email with study log-in details) 
• 
Summary for clinicians (summary of the study for clinicians)