Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU) has enabled relevant interested parties (particularly patients, researchers, and healthcare personnel), from Sweden and other countries, to agree on which outcomes should be included in a Core Outcome Set (COS) for future research studies in the treatment of antenatal and postpartum depression. In total, the COS included nine outcomes (Table 1).
|Table 1. outcomes included in the core outcome set|
|* Outcomes which are included in the COS, based on the results of survey 2 the remaining outcomes were included after discussions during the consensus meeting.|
|Self-assessed symptoms of depression, assessed with a scale that captures differences in sleep*|
|Diagnosis of depression as assessed by a clinician should include a structured interview|
|Parent to infant bonding|
|Self-assessed symptoms of anxiety|
|Quality of life|
|Satisfaction with the study intervention|
|Suicidal thoughts, attempts or completed suicide*|
|Thoughts of harming the baby, including thoughts of extended suicide*|
|Adverse events including spontaneous or induced abortion, miscarriage, fetal death and neonatal death|
A core outcome set (COS) is an agreed standardised set of outcomes that should be assessed and reported, as a minimum, in all clinical trials in specific areas of health or health care. The outcomes that are to be included in different COS are selected by a consensus process, in which healthcare personnel, researchers, and patients should be included. By developing and implementing COS, the aim is to enable the results from various studies to be more readily comparable and synthesised, and that the basis for decisions, for patients and healthcare personnel, will therefore be strengthened (Figure 1).
Figure 1 A schematic picture of the intended use of Core Outcome Sets
Development of a COS for future research studies in the treatment of antenatal and postpartum depression.
The primary target groups for this report are researchers and research funders. The project has been commissioned by the Swedish government as part of its efforts for the promotion of women’s health. This is the first time SBU has facilitated the development of a COS.
The area of antenatal and postpartum depression was chosen based on the results from an overview of existing and ongoing COS within the field of maternal health .
The project was registered in the COMET initiative registry  and is developed according to theCOS-STAD Recommendations . The project followed an a priori established protocol (Appendix 1).
The study consisted of three parts: (1) a systematic overview of the outcomes reported in systematic reviews and randomised controlled trials (RCTs) published 2018-2019, as well as in ongoing RCT on the topic, (2) a two-round Delphi survey with relevant stakeholders to prioritise the outcomes used in the studies, and (3) a consensus meeting where the final COS is decided (Figure 2). The project does not address the questions of which method should be applied to assess the outcomes, or when the outcomes should be assessed.
Figure 2 Flow chart of the project.
Identifying outcomes in research
In order to identify outcomes used in current research, a literature search for relevant randomised controlled trials (RCT) and systematic reviews published 2018–2019 as well as study protocols for RCT (no time limit) was undertaken (search strategy presented in Appendix 2).
- Pregnant women, or their partners suffering from depression
- New mothers or their partners suffering from depressions
Any intervention given for depression
Any type of control was accepted
Outcomes relating to the effect of the treatment given
Randomised controlled trials or systematic reviews. Both protocols and published studies were included.
Conference abstracts, studies investigating prevention of depression and studies investigating treatments given to persons suffering from a combination of depression and other chronic conditions such as HIV infection, were excluded.
No language restriction applied to the search strategy, but the final inclusion was only for studies in English or Scandinavian languages
From 2018 to 2019 (clinicaltrials.gov no time restriction). Final search September-October 2019 (full search strategy presented in Appendix 2)
Medline (OVID), Cochrane library (Wiley), PsycINFO (EBSCO), Cinahl (EBSCO) and ClinicalTrials.gov
All identified studies were screened for relevance independently by two members of the study management. Data were extracted by one review author and checked by another review author.
Following data were extracted from the studies:
- Study design
- Year for publication
- Intervention/s used
- Outcomes, with notification if outcomes are stated as primary or secondary
- Toll for outcome measure
- Time for outcome measure
After extraction, the identified outcomes were analysed and all outcomes that are unique were listed. Some of very similar outcomes in that list were brought together, for example outcomes measuring different hormonal or pharmaceutical levels were combined as under biological parameters.
Development of a Core Outcome Set
This process comprises a two-round Delphi survey and a consensus meeting. Relevant stakeholders (the working group) participated in the entire process, giving their perspectives on which outcomes are so important that they should be included in the COS. To allow international participation, all material was translated into English and information about the project was disseminated both within Sweden and internationally. In all, 222 people expressed an interest in participating, of whom 24 were international participants (Table 3). All participants belonged to one of the following four stakeholder group:
- Patient- or relative
- Researcher within the field
- Health professional
- HTA-agencies policy makers and others
In the Delphi study, all participants independently ranked the various outcomes in terms of importance and relevance, in two consecutive surveys. The information sent to the participants are presented in Appendix 3. Before they answered the second survey, they were shown how the different stakeholder groups, had ranked the outcomes in the first survey. In the first survey there was also an opportunity to suggest additional outcomes which were not identified in the actual research. The results of the surveys were analysed according to previously determined criteria, as to whether the outcome should be included in the COS. One exception from the pre-set protocol was made after the Delphi process. This to enable all outcomes included in the consensus meeting to be properly discussed. In total 23 outcomes were passed forward to the consensus meeting. Based on the results from the second survey three outcomes (marked with * in Table 1) were classified as consensus in, and thereby included in the COS. In addition, outcomes fulfilling the below specified criteria where discussed during the meeting:
- Any outcome for which at least 70% of participants in either one of the stakeholder group scored as critically important (7–9)
- The ten outcomes given the highest scores by each stakeholder group
The entire process concluded with a meeting at which a selection of the participants who had been in the Delphi study reached consensus about which further outcomes, over and above those which had already met the inclusion criteria, should be included in the COS. After the consensus meeting, all those who had completed the second questionnaire were given access to, and the option of making comments on, the final COS.
Identifying outcomes in research
A total of 165 studies (Figure 3) were included and are described in further detail in Appendix 4. Excluded studies with reason for exclusion are presented in Appendix 5. On the basis of the included studies, a list was made of 93 different outcomes which were used in the research. As well, a further 13 outcomes were added by the project participants. Thus, in all, 105 outcomes were included in the consensus process. On average, the RCT: s contained six outcomes and the systematic reviews four outcomes (Table 2). The three most common outcomes in the included studies were self-assessed symptoms of depression, clinical diagnosis of depression and self-assessed symptoms of anxiety.
Table 2 Summary of results from the systematic overview of outcomes.
|Number of studies||Antenatal depression||Postpartum depression||Both antenatal samt postpartum depression||Number of outcomes in the studies, Median; Mean (min–max)|
|RCT-protocol||104||33||60||11||5; 6 (1–24)|
|27||12||12||3||5; 6 (1–19)|
|Systematic reviews published
|34||8||16||10||2; 3 (1–13)|
|Total||165||53||88||24||5; 6 (1–24|
Figure 3 Flow Chart.
Development of a Core Outcome Set
A flow chart describing the different steps of the development of the COS are presented in Figure 4.
Figure 4 Flow chart of the different steps in the development of the Core outcome set.
Out of the 222 people who expressed an interest to partake in the project, 151 completed survey 1 and 123 completed survey 2 (Table 3). All outcomes included in the survey and a summary of the results are presented in Table 4. A more detailed presentation of the results from survey 1 and survey 2 are available in Appendix 6 and Appendix 7).
Table 3 Characteristics of participants in the Delphi online survey.
|* Brazil (n=1), Norway (n=1), United kingdom (n=4), Ireland (n=7), Finland (n=1), Germany (n=2), China (n=2), Nigeria (n=1), France (n=1), Holland (n=1), Portugal (n=1), India (n=1), Israel (n=1).|
|Signed up for participation||Completed survey 1||Completed survey 2||Participated in consensus-meeting|
|Researcher within the field||41||30||31||3|
|HTA-agencies, policy makers and others||13||11||9||2|
|Patient- or relative||69||43||33||4|
|Total (from countries other than Sweden)||222 (24*)||151 (20)||123 (18)||13 (0)|
After analysing the result of both surveys, three outcomes met the criteria for inclusion in the COS (marked * in Table 1). As well as these three outcomes, a further 20 were discussed during the consensus meeting.
Table 4 Summary of results from survey 1 and 2. Highlighted in Bold are outcomes discussed during the consensus meeting.
|a Indicates that the outcome has been listed as primary in at least one study.
b The outcome has only been identified in studies on antenatal depression.
c The outcome has only been identified in studies on postpartum depression.
d The outcome has been added by the project management.
e The outcome has been added by participants in the delphi survey.
|Survey 1||Survey 2||Number of studies including this outcome (of 165)|
|Outcome||Number of replys||Median (IQR1-IQR3)||Number of replys||Median (IQR1-IQR3)|
|Depressive symptoms||149||7 (6–9)||123||8 (7–9)||133a|
|Depression in partner||144||6 (4–7)||123||5 (4–6,5)||1|
|Psychiatric diagnosis of depression||147||7 (6–8)||119||8 (6–9)||57a|
|Recovery from depression (remission)||146||7 (6–8)||121||7 (5–8)||17a|
|Depression relapse||144||7 (6–8)||121||7 (6–8)||4a|
|Time to remission from depression||143||6 (5–8)||122||6 (5–7)||1a,c|
|Was depression treatment initiated||145||7 (6–9)||122||7 (6–9)||6a|
|Change in antidepressant medication||141||6 (4–7)||120||6 (4–7)||3|
|Expert rating of overall disease burden||137||6 (4–8)||118||6 (4–7)||17a|
|Anxiety symptoms||141||7 (6–8)||119||7 (5–8)||51a|
|Fear of childbirth||142||6 (4,25–8)||119||6 (4,5–8)||0d|
|Psychiatric diagnosis of anxiety||141||7 (5–8)||118||6 (5–7)||8a|
|Other psychiatric or neuropsychiatric diagnoses||138||6 (5–7)||117||6 (5–8)||2b|
|Mood||139||6 (5–8)||119||6 (5–8)||5|
|Self-harm||141||7 (6–8)||118||7 (6–9)||0d|
|Suicidal thoughts or attempts or completed suicide||140||9 (7–9)||114||9 (8–9)||10a|
|Cognitive ability||143||6 (4–7)||117||5 (4–7)||4|
|Eating disorder symptoms||138||6 (4–7)||118||5 (4–6)||2|
|Visit to clinic for fear of childbirth||141||6 (4–8)||118||5 (4–7)||0d|
|Post-traumatic stress symptoms||141||7 (6–8)||119||7 (4,5–8)||1b|
|Psychiatric diagnosis of postpartum stress syndrome in relation with childbirth||141||7 (5–9)||117||7 (5–8)||0d|
|Psychiatric diagnosis of postpartum psychosis||138||7 (6–9)||115||7 (6–9)||0d|
|Domestic/ intimate partner violence||136||8 (5–9)||118||7 (6–9)||1c|
|Family functioning||137||6 (5–8)||119||6 (5–7)||4|
|Quality of relationship||139||5 (4–7)||119||5 (4–6)||9a|
|Parent to infant bonding||140||7 (6–9)||119||7 (6–8)||18|
|Attachment||139||8 (6–9)||118||7 (5,25–8)||2a,c|
|Parenting Sense of Competency||139||6 (5–8)||119||6 (5–8)||13a|
|Parental stress||139||6 (5–7)||118||6 (5–7)||15a|
|General stress||139||6 (4–7)||118||6 (4–6)||5|
|Parent-infant interaction||138||7 (6–9)||116||7 (5–8)||11a|
|Attitudes about parenting||137||6 (4–7)||117||5 (3–6)||4|
|Family planning||141||5 (4–7)||118||4 (3–6)||1b|
|Daily functioning level/ activities of daily living||137||6 (5–8)||119||6 (5–7)||23|
|Sleep||138||7 (6–9)||119||7 (5,5–8)||8a|
|Fatigue||137||6 (5–8)||119||6 (5–8)||2c|
|Quality of life||140||6 (5–8)||117||6 (5–8)||26a|
|Sexual desire/function||135||5 (3–6)||119||4 (3–6)||1c|
|Stigma||138||6 (4–8)||117||6 (4–7)||2b|
|Social relationships||138||6 (5–7)||119||6 (4–7)||9|
|Perceived ability to cope with life challenges||136||6 (4,75–7)||117||6 (4–7)||1c|
|Effort-based decision-making||135||6 (4–7)||118||5 (4–6)||4b|
|Self-compassion||135||5 (4–7)||117||5 (3–6)||1b|
|Lifestyle||134||6 (4–7)||116||5 (4–6)||1b|
|Verbal fluency||122||3 (2–4)||108||3 (2–5)||1|
|Personality||128||4 (3–6)||112||3 (3–5)||2|
|Perceived social support / Help-Seeking||137||7 (5–8)||117||6 (5–7)||12|
|Socio-emotional competence||131||6 (4–7)||117||5 (4–6)||4|
|Confidence to self-help||133||6 (4–7)||116||5 (3–7)||3|
|Mentalizing, reflective functioning and level of mindfulness||133||5 (4–7)||116||5 (3–6,25)||5a,c|
|Self-esteem||135||6 (4–8)||117||6 (4–7)||3|
|Adverse event||133||7 (5–8)||116||6 (5–8)||29a|
|Spontaneous abortion or stillbirth||127||7 (6–9)||112||8 (5–9)||1b|
|Perinatal mortality||126||8 (6–9)||111||8 (6–9)||1b|
|Infections during pregnancy||119||5 (3–6)||108||4 (3–6)||1b|
|Residual physical problems after delivery||133||7 (6–9)||115||7 (5–8)||4a,b|
|Birth injury||130||6 (5–9)||115||7 (5–8)||5|
|Pain||131||6 (4–7)||115||6 (4–8)||1b|
|Gestational hypertension or preeclampsia||124||6 (4–7)||103||5 (4–7)||3b|
|Gestational age at delivery||130||6 (5–8)||111||6 (4–7)||5b|
|Gestational diabetes||121||5 (3–7)||107||5 (3–7)||1b|
|Estimated blood loss||121||6 (4–7)||105||5 (3–7)||2b|
|Induction of labour||126||6 (4–7)||110||5 (4–7)||1b|
|Mode of delivery||132||6 (5–8)||114||6 (4–8)||6a|
|Fetal growth assessment by ultrasound||124||5 (4–7)||108||5 (3–6)||1b|
|Complications associated with the placenta||117||5 (3–7)||108||5 (3–7)||1b|
|Vaginal and/or faecal microbiota||107||3 (3–6)||102||3 (3–5)||1b|
|Transition of care from pregnancy to postpartum||133||7 (6–9)||115||7 (5–9)||1a,b|
|Breastfeeding||131||6 (4–8)||114||6 (4–7)||8|
|Child attention||126||5 (4–7)||109||5 (4–6)||3c|
|Duration of crying episodes||127||6 (4–7)||109||5 (3–6)||1b|
|Child development||133||7 (5–8)||112||6 (5–8)||19a|
|Neurodevelopmental and neurobehavioral outcomes||128||7 (5,75–8)||111||7 (5–8)||2a,c|
|Infant sleep||131||6 (5–7)||112||6 (4–8)||1b|
|Vaccinations received/ Immunization status||123||4 (2–6)||109||3 (2–6)||4|
|Infant or child’s temperament||132||5 (4–7)||112||4 (3–6)||6a|
|Biological parameters in the infant||110||5 (3–7)||96||4 (3–6)||6|
|Well-baby check-up status||132||6 (4–7)||111||5 (3–7)||2|
|Congenital malformations||125||6 (4–8)||104||6 (4–7)||1b|
|Infant antibiotic use||117||4 (3–6)||100||3 (3–5,25)||1b|
|Birth weight, height and head circumference||126||5,5 (4–6)||106||5 (3–6)||8a|
|Small for gestational age (SGA)||123||6 (4–7)||105||5 (4–7)||3b|
|Apgar score||123||5 (4–7)||106||5 (3–7)||4a|
|Neonatal intensive care unit admission||126||6 (5–8)||106||6 (5–8)||4|
|Cost-effectiveness||130||6 (4–7)||106||5 (4–7)||9a|
|Use of health services||131||6 (4–7)||110||5 (4–6)||16|
|Engagement and retention with health services||133||6 (4–7)||109||5 (4–6)||3|
|Sick-leave||133||6 (4–7)||113||6 (4–7)||3|
|Satisfaction with intervention||136||7 (6–8)||114||7 (6–8)||31a|
|Therapeutic alliance||135||7 (6–9)||113||7 (6–9)||2|
|Quality of care||136||6 (5–8)||114||7 (5–8)||5|
|Parent experience||133||7 (6–8)||114||7 (5–8)||2a|
|Pregnancy/ delivery experience||135||7 (5–9)||114||7 (6–9)||2a,b|
|Biological parameters||112||5 (4–7)||99||4 (3–6)||15a|
|Maternal vital signs/ physical examination||116||4 (3–6)||101||4 (3–6)||6a|
|Knowledge about anti-depressant treatment in pregnancy||128||5 (4–7)||110||5 (4–7)||2b|
|Partner’s attendance||135||6 (5–7)||114||6 (4–7)||2|
|Coping strategies among relatives||126||5,5 (4–7)||112||5 (4–6,25)||1b|
|Separation or divorce||-||-||112||5 (3–7)||0e|
|Ability to return to work/ change of work||-||-||113||5 (4–7)||0e|
|Obsessive thoughts or intrusive thoughts||-||-||110||6 (4–7)||0e|
|Fear of something bad happening to the baby||-||-||113||6 (4–8)||0e|
|Thoughts of harming the baby, (including thoughts of extended suicide)||-||-||113||8 (7–9)||0e|
|Level of compliance with the given treatment||-||-||112||7 (6–8)||0e|
|Mental health literacy||-||-||113||6 (4–8)||0e|
Thirteen people participated in the consensus meeting: all four stakeholder groups were represented. During the meeting the group agreed on inclusion of a further six outcomes in the COS and also to amend the formulation of some of the included outcomes. No further comments were received from other participants with respect to the COS which was developed during the consensus meeting. The outcomes which are included in the final COS are described in Table 1.
The aim is that the outcomes included in this COS are to be measured in future studies and systematic reviews of treatment of antenatal and postnatal depression (intervention studies). If this is achieved it will result in improved potential to synthesise the results from different studies. In the long term this will lead to a stronger evidence. This can be important for some of the outcomes which occur less frequently, for example suicide, and where a large patient material is necessary in order to discern differences between various treatment methods. Most of the outcomes in the agreed COS are currently used in research (Figure 5). However, only one of the selected outcomes, self-assessed symptoms of depression, is used in more than 50% of the identified studies. The second most commonly used outcome, diagnosis of depression as assessed by a clinician only occurred in 33%.
Figure 5 Frequency of the COS included outcomes in the identified studies.
In the protocol for the present study the maximum number of outcomes to be included in the COS had already been limited to ten. We believe that a greater number is not practical. After going thru the actual studies in this field, we can state that generally they contain around six outcomes, i.e. fewer than the number included in this COS. Thus, despite our ambition to try to limit the number of outcomes, the nine outcomes included in this COS, may be to many. This might lead to difficulties for researchers to include further outcomes specific to the research question. This project has not addressed how and when these outcomes should be measured, directives that should be included in a comprehensive COS. We intend, however, to pursue these questions in a future project.
This COS included an outcome which has not been identified in any study, namely ”thoughts about harming the child”. This highlights the need to involve patients, healthcare personnel and researchers in the process of selecting which outcome to include in a COS, and also to encourage the project participants to suggest outcomes over and above those which are already used in research.
SBU would like to thank all those who have been involved in, or assisted in dissemination of information about, the project, especially all those who participated in the development of the COS.
- Maria Jonsson, Associate professor and senior consultant at the Department of Obstetrics and Gynecology, Uppsala university hospital, Sweden.
- Alkistis Skalkidou, Professor of Obstetrics and Gynecology, Dept. of Women’s and Children’s Health, Uppsala University and senior consultant at the Gynecologic Department, Uppsala university hospital
- Frida Trönnberg, Patient representative
- Christel Hellberg (Project Manager)
- Marie Österberg (Project Manager)
- Ann-Kristine Jonsson (Information Specialist)
- Sara Fundell (Project Administrator)
- Erik Forsell, PhD, Research and Development-Psychologist
- Ann Josefsson, Professor, Senior consultant in Obstetrics and Gynecology
- Sverker Svensjö, PhD, Senior Consultant, Surgery
- SBU. Core outcome sets inom förlossningsvård. Sammanställning och analys av studier. Stockholm: Statens beredning för medicinsk och social utvärdering (SBU); 2020. SBU-rapport nr 309. ISBN 978-91-88437-51-8.
- COMET Initiative. COMET Database. Treatment of perinatal depression: protocol for a systematic review of outcomes in the literature and identification of a core outcome set using a Delphi survey. [cited 2020 April 1]. Available from: http://www.comet-initiative.org/Studies/Details/1421.
- Kirkham JJ, Davis K, Altman DG, Blazeby JM, Clarke M, Tunis S, et al. Core Outcome Set-STAndards for Development: The COS-STAD recommendations. PLOS Medicine 2017;14:e1002447.
SBU Policy support identifies and presents available scientific evidence to support policy and decision making, including the development of national guidelines, at other government agencies. In consultation with professional experts, SBU staff generates supporting documentation to address the various questions that have been posed.
|Registration no:||SBU 2019/290|