The study will be conducted in purposively selected primary healthcare facilities in Sodo and Kibet districts of the Southern Nations, Nationalities and Peoples’ Region (SNNPR). The primary healthcare facilities, primary hospitals and health centres, are staffed by nurses, midwives and health officers. Each health centre is linked to about five health posts, community-based health facilities staffed by health extension workers (HEWs). HEWs are community-based healthcare workers who provide the first antenatal contact, before referring women for further ANC at a health centre or primary hospital, and maintain contact with women during pregnancy.
The study sites are located 100-150km south of Addis Ababa, the capital city of Ethiopia. Kibet district is in the Silte Zone. Sodo district is one of 15 districts in the Gurage zone of SNNPR. Sodo is where the UK Department for International Development-funded Programme for Improving Mental Health carE (PRIME) (44) worked with local leaders and stakeholders to develop and implement a mental health care plan based on task-shared mental health care delivered in primary and maternal health care settings. The official language of the region and in both districts is Amharic.
The proposed study is a randomised, controlled feasibility trial with two parallel groups and three time point assessments: at baseline, nine weeks after recruitment and 4-6 weeks postnatal (Figure 1). A mixed qualitative and quantitative methods process evaluation will be nested within the trial. A second feasibility trial involving a sub-sample of trial participants who report past-year exposure to intimate partner violence will be nested within the trial; detailed in the published trial protocol (45).
Randomised, controlled feasibility trial
The randomised, controlled feasibility trial will compare the adapted PST with enhanced usual care (EUC). Eligibility criteria, participant recruitment procedures, sample size, and randomisation procedures, intervention delivery, assessment and data analysis methods will be described in the following sections.
Inclusion criteria: Women can be included if they: (1) endorse elevated and disabling depression symptoms (scoring 5 or more on the locally validated Patient Health Questionnaire (PHQ-9) (46) and endorse impaired functioning on the 10th PHQ-9 item); (2) are between 12 and 34 weeks gestation; (3) are aged 16 years and above, as this is the age at which married adolescent women become legally autonomous in Ethiopia; (4) are planning to live in the study area for at least six months; (5) speak Amharic (the official regional language).
Exclusion criteria: Women will be excluded if they: (1) present with acute medical illness or evidence of severe mental illness; or (2) other comorbid medical conditions such as hypertension or renal disease or diabetes; (3) endorse the 9th item of the PHQ-9 indicating risk of suicide and scoring more than 17 on the Mini International Neuropsychiatric Interview (MINI) (47); (4) require emergency treatment; or (5) have a condition that impairs their capacity to understand the interview (e.g. diagnosed with severe intellectual disability or dementia).
Participant recruitment and screening
Consecutive women attending primary health care-based antenatal care in two primary care facilities will be the target sample for recruitment into the study (Figure 1) after the research staff obtains informed consent. The research staff will check initial eligibility of antenatal attendees based on information available from the clinical records (gestational age, age, co-morbid conditions and residence). Eligible women will be invited to provide informed consent to an initial screen for depressive symptoms associated with functional impairment using the PHQ-9 and the PHQ-9 disability item. The disability item asks “Over the last two weeks, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?” The response options are: “Not difficult at all”=0, “somewhat difficult”=1, “very difficult”=2 or “extremely difficult”=3. The MINI will be administered to women who endorse any frequency of suicidality on the ninth item of PHQ-9. Women with risk of suicide (MINI≥17) (47) will be excluded from the study and referred for review by a mental health-trained primary care worker (30) who will employ mhGAP (48) to assess risk of suicide. The research staff will facilitate women’s attendance of services at the referral sites and their transportation costs to access care.
Any woman who is found to be eligible following the initial screen will receive written and verbal information about the study from research staff and invited to participate. Women who provide informed consent to participate in the trial will receive a fully structured baseline interview after receipt of their routine clinical care.
Participants’ costs incurred to attend research interviews and PST sessions will be reimbursed. Time spent during research interviews will be compensated, but time spent attending PST sessions will not be compensated to avoid incentivising engagement with the intervention. The healthcare workers will be compensated for their additional effort in the trial.
Fifty participants (25 in the intervention and 25 in the enhanced usual care group) will be recruited for this feasibility trial. This sample size will enable us to detect a dropout rate of 7% with 95% confidence interval and a 5% margin of error (49). A sample size of 24-50 is recommended for feasibility studies (50).
Randomisation, allocation concealment and masking
Randomisation will be stratified by women’s report of exposure to intimate partner violence, in order to accommodate the nested feasibility trial (45). Women with disabling antenatal depressive symptoms but no exposure to IPV will be randomised to one of two arms (the PST intervention or enhanced usual care) using simple randomization in a 1:1 ratio. Women with both disabling antenatal depression and intimate partner violence will be randomised to one of three arms: the PST intervention arm, enhanced usual care arm and a third arm of PST adapted for women exposed to intimate partner violence. Analysis of this third arm’s results will be confined to the nested study (Figure 1).
Central telephone randomisation will be used to conceal allocation of the participants. A data manager in the Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), external to the study, will allocate each participant to a study arm (PST, PST adapted for women exposed to IPV, or enhanced usual care) using a random number list generated by a statistician independent of the research team working in the field (GM). Separate members of research staff based in Sodo/Silte will telephone the data manager to arrange allocation of each new participant. Whenever a new participant has been allocated to that intervention, research staff will inform a clinician trained to deliver the relevant arm. Intervention and control groups will be anonymously coded so that the data analysts remain masked during analysis. Participating women and healthcare providers will not be masked to allocation status due to the nature of the intervention; however, outcome assessors will be masked to allocation status.
PST is a commonly used psychotherapy (37, 51) that has comparable efficacy to other psychotherapies such as behavioural activation, Cognitive Behavioural therapy and social skills training and medication (52, 53). The PST approach assumes that depressive symptoms are the negative consequences of maladaptive coping in response to problems (54). The intervention applies principles of evidence-based problem-solving therapy (54) to improve a person’s problem solving and coping skills. In this approach, there are three phases. In the first phase, women are helped to identify the most important things in their life. In the second phase, they identify a list of problems that challenge attainment of important goals in their life and classify the problems into three categories: ‘Problems that are upsetting but not relevant to the most important things in one’s life’ (Group A); ‘Problems that are important but, insoluble’ (Group B) and ‘important and soluble problems’ (Group C). Any psychological therapy should be adapted to the cultural setting to ensure effectiveness, acceptability and feasibility (55). PST has been contextually adapted and manualised for pregnant women with antenatal depressive symptoms in rural Ethiopia (Bitew, 2020, unpublished). The adaptation was based on the Medical Research Council guidelines for denveloping and evaluating complex interventions (33) and the ADAP-ITT approach (34). This comprised a series of theory of change workshops, adaptation workshops, and in-depth interviews with women with a history of perinatal depression and healthcare providers, and discussions after role play (theatre test).
Participants randomised to the intervention arm will receive four individual sessions of locally adapted and manualised PST, along with enhanced usual care, at a time convenient to them in a private room of the PHC facility. Intervals between sessions will range from a minimum of 2 days to a maximum of two weeks over a period of eight weeks ensuring that all sessions are completed during pregnancy. The first session will last for one hour and the remaining sessions will last for approximately forty minutes each.
The general approach to treatment is introduced in the first session, during which the structure of PST is fully explained, the participant identifies the most important priorities in her life, and a list of her current problems is established and classified into the three problem categories: Group A, Group B and Group C problems. In each session, at least one ‘problem busting session’ or ‘Group C’ problem, important to the participant and that can potentially be solved, will be discussed and the participant will agree a ‘take home activity’ based on that problem.
The second session will recap on the previous session, review the outcome of the first take-home activity, introduce problem solving strategies for problems categorised as ‘Group A’ and include one problem busting session for a group C problem. The third session will review the outcome of the second take-home activity, introduce strategies for problems categorised as ‘group B’ and include one or two problem busting sessions for ‘group C’ problems. The final session will recap the third session and include a problem busting session for any problems which the participant wishes to prioritise.
Trained healthcare workers will deliver the intervention under the supervision of an Ethiopian clinical or counselling psychologist (master’s level) or psychiatrist/psychiatric resident trained in psychological therapies. Healthcare worker training will consist of: (a) a five day classroom-based training course which includes training on counselling and communication skills as well as PST-specific skills, and (2) accelerated delivery of four sessions of PST, using high-intensity supervision and feedback to build competency (56, 57). Competency will be established using the Enhancing Assessment of Common Therapeutic factors (ENACT) scale (56, 57) administered by trained clinicians. The healthcare worker will be required to score level 3 (“Done Well”) out of the three levels: (“Done Well”, “Done partially” and “Need improvement”) on each of the competencies in order to participate in the trial. Feedback will be obtained from women receiving the accelerated PST intervention in the form of three structured questions with open-ended responses: (1) What parts of PST did you find helpful? (2) What parts of PST were unhelpful/ need to be improved? How should they be improved? and (3) How convenient was it for you to attend PST? How could this be improved? All intervention sessions will be audio-recorded. A random selection of sessions will be assessed by an expert who has been shown to rate reliably with kappa greater than or equal to 0.80 for repeated scoring. A checklist that contains five dimensions of fidelity (58) will be adapted and used to assess the audio records and then to give feedback focussed on intervention fidelity and core competencies in PST and communication skills. The five dimension of fidelity include: (1) adherence (extent to which program components such as program content, methods, and activities are delivered as prescribed by the model); (2) exposure (number of sessions or contacts, attendance, and the frequency and duration of sessions.); (3) quality of delivery (provider enthusiasm, interaction style, respectfulness, confidence, and ability to respond to questions and communicate clearly; (4) participant responsiveness (participants’ level of interest in the program; perceptions about the relevance and usefulness of a program; and their level of engagement, enthusiasm, and willingness to engage in discussion or activities); and (5) program differentiation (degree to which the critical components of a program are distinguishable from each other and from other programs).
Clinical records and consent forms will be kept in the research office for confidentiality. Research staff will use telephone contact to follow up participants who withdraw without reporting to the research office in order to check for unreported adverse events.
Enhanced usual care
Participants allocated to the enhanced usual care arm will receive usual antenatal care which focuses on advice about reproductive and family health issues and information about sources of general support. In addition, the Federal Ministry of Health in Ethiopia has prepared evidence-aligned guidelines on how to care for mental health problems in primary health care and maternal care settings (59). According to the guideline, primary healthcare staff are expected to detect mental health problems and to provide basic mental healthcare (non-specific psychosocial care for all and supervised prescription of antidepressant medication depending on severity) (60). All healthcare providers participating in the trial will have been trained in the World Health Organisation’s mhGAP for a minimum of five days, as per the mental health scale-up plans of the Federal Ministry of Health. As mhGAP has not been implemented at scale in Ethiopia, this represents an enhancement in usual care (61, 62).
Participants allocated to enhanced usual care and their healthcare providers will be informed about the results of screening and will receive an information sheet and sources of general psychosocial support. These women will attend three contacts: one pre-intervention assessment and two follow-up assessments at nine weeks after recruitment and 4-6 weeks after childbirth.
Assessment of trial participant outcomes
A list of assessment variables and details about their measurement is described in table 1. Assessment will be conducted at three time points: pre-intervention (T0; baseline), nine weeks after recruitment (T1; first follow-up) and 4-6 weeks after delivery (T2; second follow-up).
The primary outcome for a future efficacy trial will be change in PHQ-9 score using the locally validated Amharic version of PHQ-9 (63), assessed at T0, T1 and T2. The PHQ-9 has been widely used as a clinical outcome measure of treatment for depression (64, 65). In Ethiopia, PHQ-9 has been validated in antenatal women (66) and in primary care settings in the neighboring district of the current study, with the optimal cut-off point indicating probable depression identified as five or more in primary care attendees (46). At that cut-off, PHQ-9 had a sensitivity of 83.3% and specificity of 74.7% for detection of major depressive disorder. In previous studies, a 50% reduction in PHQ-9 depressive symptom scores (65) after 6-8 weeks was defined as treatment response. A 50% reduction of PHQ-9 score at nine weeks (T1) follow up will be defined as a treatment response for future efficacy trial.
Secondary outcomes to be collected at T0, T1 and T2 are: disability (change in WHO disability Assessment Scale, WHODAS, score) (67), anxiety [Generalised Anxiety Disorder-7 scale; GAD-7) (68)], PTSD symptoms checklist (PCL-5, (69, 70), intimate partner violence (non-graphic IPV test with five items (71) and WHO multi-country study questions (72)), number of emergency healthcare visits and costs (locally adapted Client Service Receipt Inventory (CSRI) (73)).
At T2 only (4 to 6 weeks postnatal) self-reported information on delivery setting, prolonged labour, sepsis, unsafe abortion, perinatal mortality (stillbirth and neonatal mortality), time of onset of breast-feeding and child health (maternal report of diarrhoea, fever and refusal to breast feed) will be collected.
Potential mediators will be assessed at T0, T1 and T2: attitudes towards gender roles (attitude towards gender roles scale (74)), mastery (Multicultural mastery scale (75)), self-efficacy of coping with depression (adapted self-efficacy scale (75)), and perceived social support (Oslo Social Support Scale (OSS-3)), previously used in Ethiopia (76). (Table 1).
At T0, a questionnaire will collect data about socio-economic and demographic characteristics of the participants (age, education, marital status, age at marriage, husband’s occupation and educational level, residence and pregnancy intention), obstetric history, including parity, pregnancy intention, and gestational age, past psychiatric history and list of traumatic experiences. An item from Ethiopian Demographic Health Survey (EDHS (previously used in our study (7)) will be used to assess pregnancy intention.
Mixed quantitative and qualitative methods process evaluation
A mixed quantitative and qualitative methods process evaluation will be nested within the feasibility trial. The aims are (1) evaluate the feasibility and acceptability of trial procedures, and (2) to investigate the implementation (feasibility, fidelity and acceptability) of delivery of PST.
Trial participant women, research assistants, supervisors and intervention providers will be included in this mixed study design.
Women who received the intervention will be purposively selected for semi-structured interview based on their status of completion of the intervention sessions (four sessions of PST). We estimate that about eight participants, both who did and did not complete the PST sessions, will be selected. However, the number of participants will depend on when no new information is obtained. All research assistants, supervisor and providers will be invited to participate in the FGDs. Two separate FGD sessions (one for providers and second for supervisors and research assistants) will be conducted.
Process evaluation outcomes
The nested process evaluation investigates two categories of feasibility/implementation outcomes: trial procedure feasibility and acceptability (See: Table 2) and implementation of delivery of PST (Table 3). The primary outcome for feasibility trial procedures is dropout rate. Dropout will be defined as the number of women lost to follow up at either of the follow up assessments. Secondary outcomes related to trial procedures and data collection procedures are listed in Table 2. These include: participant recruitment rate, feasibility and suitability of eligibility criteria, feasibility of data collection procedures (clarity of baseline questionnaires, characteristics of outcome measures such as missing data, time needed to complete the questionnaires and data collection), adequacy of masking and practical administrative challenges, and acceptability of trial procedures (number of refusals to recruitment and screening; qualitative exploration of experience of trial procedures).
To document the successful implementation of an intervention, the following implementation outcomes are recommended: acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, and sustainability (77) as detailed in Table 3.
The primary outcome of the feasibility study, dropout from the trial, will be documented as part of routine administrative data. Administrative documents, log books, FGD with research assistants and supervisors and proceedings of supervisory team will be used to document data about these primary and secondary trial procedure outcomes.
Two categories of assessment tools will be employed to assess the PST delivery implementation outcomes: (1) qualitative data (interview, FGD, audio recorded sessions) and (2) assessment tools (outcome assessment tools, Helping Alliance Questionnaire (HAQ), ENACT, fidelity checklist). See table 3 for an overall summary of the data to be collected to document PST delivery implementation outcomes. Semi-structured interviews will be carried out with research assistants, supervisors and participants who received the intervention and FGDs with providers of the intervention to investigate acceptability and feasibility of the intervention delivery. Semi-structured interviews with women who received the intervention will make use of the same three structured questions with open-ended responses that were used as a competency check during provider training ((1) What parts of PST did you find helpful? (2) What parts of PST were unhelpful/ need to be improved? How should they be improved? and (3) How convenient was it for you to attend PST? How could this be improved?). The interview topic guides with participants will focus on any perceived benefits of the intervention, challenges of delivering and receiving the intervention and the strengths and weaknesses of intervention delivery and their experience of the intervention delivery.
Intervention sessions will be audio recorded and some randomly selected participants’ sessions will be assessed. Expert who rated the intervention sessions during provider training will rate the sessions using the checklist described previously that contains five dimensions of fidelity (58). FGD topic guides for providers, supervisor and research assistants will focus on reflection of their experiences about the intervention, including opportunities and challenges related to intervention delivery in routine settings.
Data collection procedures and quality
Double data entry will be used for the quantitative data. Range checks will be done for data values. For qualitative data, the data will be collected from multiple sources (supervisors, research assistants, intervention providers, women receiving the intervention) for triangulation. Experienced qualitative data collectors with master’s degree and above will conduct the semi-structured interviews and facilitate the FGDs. Audio records of selected PST sessions, in-depth interviews to elicit women’s feedback about delivery of the intervention and from FGDs will be transcribed verbatim and translated into English.
Trial participant outcomes
Descriptive statistics will be used to summarize trial participant characteristics and future efficacy trial outcomes. The proportion of each group meeting criteria for treatment success (a 50% reduction of PHQ-9 score at T1) and mean change in PHQ-9 score will be described for the two arms. All outcomes (measured at T1 and T2) will be summarized for PST and enhanced usual care arms. For continuous outcomes, the standard deviation will be computed, to inform future sample size calculations for the main study. Standard deviation will be computed from participants for whom outcome measures are available without need of imputations.
Process evaluation outcomes
Descriptive statistics will be used to summarize participant characteristics, the primary outcome and secondary quantitative outcomes of trial procedures and PST delivery implementation outcomes such as extent of missing data, numbers of sessions attended, number of homework activities attempted, rates of initial engagement, providers’ fidelity to the intervention protocol and rates of recruitment. The transcripts will be coded for thematic analysis to identify issues related to context, mechanisms and implementation as suggested in key guidance for the systematic conduct of process evaluations of complex interventions (78).