Ethical issues in randomised clinical trials for adolescents who self-harm: The limits of equipoise and evidence in the cultural context of Pakistan

This research examined the main conceptions of equipoise and applied them in a different cultural context based on a Randomised Clinical Trial (RCT) being conducted in Pakistan, which is investigating a psychological intervention YCMAP plus treatment as usual versus treatment as usual for young people at risk of self-harm or suicide. Equipoise is the moral justification for recruiting participants in an RCT, when there is uncertainty about which arm of the trial is more beneficial to the patient. The current research focused on whether the clinicians’ recruiting patients have a treatment preference and whether they regard participation in an RCT as scientifically and ethically important. Methods The study used an exploratory mixed methods approach; survey of clinicians, both involved and not involved in the trial and a discussion group with Pakistani researchers. It included an empirical study of the views and values of clinicians (N=20). The study examined the ethical considerations regarding clinical trials and human rights law. My thesis reviewed literature on Islamic approaches to research ethics, developed a community engagement tool for use by western researchers through a discussion group with Pakistani researchers and conducted semi structured qualitative interviews with the clinicians to explore the cultural context. Results Findings showed that clinicians (73.3%) consider YCMAP to be an effective treatment for young patients at risk of self-harm or suicide. Although, there was acknowledgement of individual preferences, there was greater consensus on the need to conduct an RCT for reaching an evidence-based decision. Conclusion From my research, I conclude that there was enough evidence of uncertainty and the existence of clinical equipoise as moral justification for conducting the RCT. There was a desire to gather home grown evidence base to make it more culturally relevant. Religiosity was a dominant thread across all the themes from the cultural analysis

Is equipoise a useful concept to justify randomised controlled trials in the cultural context of Pakistan? A survey of clinicians in relation to a trial of talking therapy for young people who self-harm

Background: Clinical equipoise, also defined as the uncertainty principle, is considered essential when recruiting subjects to a clinical trial. However, equipoise is threatened when clinicians are influenced by their own preferences. Little research has investigated equipoise in the context of trial recruitment. Methods: This cross-sectional survey sought clinicians’ views (operationalised as 11 statements relating to treatments offered in a trial of a psychological intervention for young people) about equipoise and individual treatment preferences in the context of moral justification for recruiting young people at risk of self-harm or suicide to a randomised controlled trial (RCT) to evaluate the Youth Culturally Adapted Manual Assisted Psychological Intervention (Y-CMAP) in Pakistan. We compared the views of clinicians involved in Y-CMAP RCT recruitment to those of a sample of clinicians not involved in trial recruitment but treating similar patients, comparing their sociodemographic characteristics and the proportions of those in each group agreeing with each statement. Results: There was a response rate of 96% (75/78). Findings showed that, during trial recruitment and before the RCT results were known, the majority of all responding clinicians (73.3%) considered Y-CMAP to be an effective treatment for young people at risk of self-harm or suicide. Although there was an acknowledgement of individual preferences for the intervention, there was near consensus (90%) on the need to conduct an RCT for reaching an evidence-based decision. However, there were no significant differences in the proportion of recruiting clinicians reporting a treatment preference for Y-CMAP than non-recruiting clinicians (31 (88.6%) versus 36 (90%), p = 0.566). A significantly higher proportion of non-recruiting clinicians (87.5%) as compared to (48.5%) in the trial (p = 0.000) stated that there may be other treatments that may be equally good for the patients, seemingly undermining a preference for the intervention. Those reporting a treatment preference also acknowledged that there was nothing on which this preference was based, however confident they felt about them, thus accepting clinical equipoise as ethical justification for conducting the RCT. There was a significant group difference in views that treatment overall is better as a result of young patients’ participation in the Y-CMAP trial (p = 0.015) (i.e. more clinicians not involved in the trial agreed with this statement). Similarly, more clinicians not involved in the trial agreed on the perceived availability of other treatment options that were good for young people at risk of self-harm (p < 0.05). Conclusions: The paper highlights that clinicians in Pakistan accept the notion of clinical equipoise as an ethical justification for patient participation in RCTs. The need for conducting RCTs to generate evidence base and to reduce bias was considered important by the clinical community

Building Resilience Against ViolencE (BRAVE): protocol of a parenting intervention for mothers and fathers with post-traumatic stress disorder in Pakistan

Abstract Background Prevalence of post-traumatic stress disorder (PTSD) is high in Pakistan both due to natural disasters and ongoing conflicts. Offspring of trauma survivors are at increased risk for mental and physical illnesses. Parental PTSD has been linked to troubled parent–child relationships, behaviour problems, trauma symptoms, and depression in children. This study aims to explore the acceptability, feasibility and indications of the effectiveness of group learning through play plus trauma-focused cognitive behaviour therapy (LTP Plus TF-CBT) for parents experiencing PTSD. Methods/Design This is a two-arm pilot cluster randomised controlled trial (RCT). We aim to recruit 300 parents with a diagnosis of PTSD. The screening will be done using the Impact of Event Scale-Revised. Diagnosis of PTSD will be confirmed using the Clinician-Administered PTSD Scale-5 (CAPS-5). Union Councils from Peshawar and Karachi will be randomised into either group LTP Plus TF CBT arm or treatment as usual (TAU). The intervention includes 12 sessions of LTP Plus TF-CBT delivered weekly in the first 2 months and then fortnightly in a group setting by trained psychologists. The groups will be co-facilitated by the community health workers (CHWs). Parents will be assessed at baseline and 4th month (end of the intervention), using the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder (GAD-7) Scale, Client Service Receipt Inventory (CSRI), and Ages and Stages Questionnaire (ASQ-3) Discussion This trial would help build an understanding of the acceptability, feasibility and indications of the effectiveness of a low-cost parenting intervention

Prevalence of depression and anxiety in patients with chronic obstructive pulmonary disease and their association with psychosocial outcomes: A cross-sectional study from Pakistan.

ObjectivesChronic obstructive pulmonary disease contributes to substantial health and economic burden worldwide. Co-morbid depression and anxiety are highly prevalent in patients with chronic obstructive pulmonary disease. Depressive symptoms in chronic obstructive pulmonary disease are associated with poorer survival, longer hospitalisation and impaired quality of life. Literature on chronic obstructive pulmonary disease is largely derived from high-income countries; yet 90% of deaths related to chronic obstructive pulmonary disease occur in low- and middle-income countries. We aimed to establish the prevalence of anxiety and depression in patients with chronic obstructive pulmonary disease, as well as the association with psychosocial outcomes.MethodsThis was a cross-sectional study of chronic obstructive pulmonary disease patients attending outpatient primary care clinics in Karachi, Pakistan. The Patient Health Questionnaire-9 was used to assess depression and the Generalised Anxiety Disorder-7 scale was used for the assessment of anxiety. Health-related quality of life was assessed with EuroQol-Five Dimensions, social support with Oslo-3 and social stress with Life Events Checklist. We recruited 293 subjects.ResultsThe prevalence of depression and anxiety in the sample was 51% (n = 149) and 20% (n = 59), respectively. Depressed chronic obstructive pulmonary disease patients reported significantly lower health-related quality of life scores as compared to non-depressed patients. Participants with depression had significantly higher levels of anxiety, less social support, higher social stress and more subjective impairment in quality of life.ConclusionGiven the association with reduced social support and increased perceived stress, the role of psychosocial interventions must be explored in improving outcomes of chronic obstructive pulmonary disease patients in Pakistan

Youth Culturally adapted Manual Assisted Problem Solving Training (YCMAP) in Pakistani adolescent with a history of self-harm: protocol for multicentre clinical and cost-effectiveness randomised controlled trial

Introduction: Suicide is a global health concern. Sociocultural factors have an impact on self-harm and suicide rates. In Pakistan, both self-harm and suicide are considered as criminal offence’s and are condemned on both religious and social grounds. The proposed intervention ‘Youth Culturally Adapted Manual Assisted Problem Solving Training (YCMAP)’ is based on principles of problem-solving and cognitive–behavioural therapy. YCMAP is a brief, culturally relevant, scalable intervention that can be implemented in routine clinical practice if found to be effective. Method and analysis: A multicentre rater blind randomised controlled trial to evaluate the clinical and cost-effectiveness of YCMAP including a sample of 652 participants, aged 12–18 years, presenting to general physicians/clinicians, emergency room after self harm or self referrals. We will test the effectiveness of 8–10 individual sessions of YCMAP delivered over 3 months compared with treatment as usual. Primary outcome measure is repetition of self-harm at 12 months. The seconday outcomes include reduction in suicidal ideation, hopelessness and distress and improvement in health related quality of life. Assessments will be completed at baseline, 3, 6, 9 and 12 months postrandomisation. The nested qualitative component will explore perceptions about management of self-harm and suicide prevention among adolescents and investigate participants’ experiences with YCMAP. The study will be guided by the theory of change approach to ensure that the whole trial is centred around needs of the end beneficiaries as key stakeholders in the process. Ethics and dissemination: Ethics approval has been obtained from the Ethics Committee of University of Manchester, the National Bioethics Committee in Pakistan. The findings of this study will be disseminated through community workshops, social media, conference presentations and peer-reviewed journals. Trial registration number: NCT04131179