Trial Of Complex Intervention Research Articles

The BrEasT cancer afTER-CARE (BETTER-CARE) programme to improve breast cancer follow-up: design and feasibility study results of a cluster-randomised complex intervention trial.

The risk of breast cancer patients for long-term side effects of therapy such as neurotoxicity and cardiotoxicity as well as late effects regarding comorbidities varies from individual to individual. Personalised follow-up care concepts that are tailored to individual needs and the risk of recurrences, side effects and late effects are lacking in routine care in Germany. We describe the methodology of BETTER-CARE, a parallel-arm cluster-randomised controlled trial conducted at 15 intervention and 15 control centres, aiming to recruit 1140 patients, and the results of the pilot phase. The needs- and risk-adapted complex intervention, based on existing development frameworks, includes a multidisciplinary network and digital platforms for symptom and need documentation and just-in-time adaptive interventions. The control group comprises usual care according to clinical guidelines. The primary outcome is health-related quality of life (EORTC QLQ-C30 global health), and secondary outcomes include treatment adherence. The 2-month pilot phase comprising 16 patients in one intervention and one control pilot centre demonstrated the feasibility of the BETTER-CARE approach. BETTER-CARE is a feasible intervention and study concept, investigating individualised needs- and risk-adapted breast cancer follow-up care in Germany. If successful, the approach could be implemented in German routine care. German Clinical Trial Register DRKS00028840. Registered on April 2022.

The influence of intervention fidelity on treatment effect estimates in clinical trials of complex interventions: A meta-epidemiological study

BackgroundRandomized clinical trials (RCT) provide the most reliable estimates of treatment effectiveness for therapeutic interventions. However, flaws in their design and conduct may bias treatment effect estimates, leading to over or underestimation of the true intervention effect. This is especially relevant for complex interventions, such as those in rehabilitation, which are multifaceted and tailored for individual patients or providers, leading to variations in delivery and treatment effects. ObjectiveTo assess whether poor intervention fidelity, the faithfulness of the intervention delivered in an RCT to what was intended in the trial protocol, influences (biases) estimates of treatment effects derived from meta-analysis of rehabilitation RCTs. MethodsIn this meta-epidemiological study of 19 meta-analyses and 204 RCTs published between 2010–2020, we evaluated the difference in intervention effects between RCTs in which intervention fidelity was monitored and those in which it was absent. We also conducted random-effects meta-regression to measure associations between intervention fidelity, risk of bias (ROB), study sample size, and treatment effect estimates. ResultsThere was a linear relationship between fidelity and treatment effect sizes across RCTs, even after adjusting for ROB and study sample size. Higher degrees of fidelity were associated with smaller but more precise treatment effect estimates (d= -0.23 95% CI: -0.38, -0.74). Lower or absent fidelity was associated with larger, less precise estimates. Adjusting for fidelity reduced pooled treatment effect estimates in 4 meta-analyses from moderate to small or from small to no negligible or no effect, highlighting how poor fidelity can bias meta-analyses’ results. ConclusionPoor or absent intervention fidelity in RCTs may lead to overestimation of observed treatment effects, skewing the conclusions from individuals studies and systematic reviews with meta-analyses when pooled. Caution is needed when interpreting the results of complex intervention RCTs when fidelity is not monitored or is monitored but not reported.

What is the carbon footprint of academic clinical trials? A study of hotspots in 10 trials

BackgroundClinical trials are fundamental to healthcare, however, they also contribute to anthropogenic climate change. Following previous work to develop and test a method and guidance to calculate the carbon footprint...

Public perspective on potential treatment intervention harm in clinical trials—terminology and communication

BackgroundRandomised controlled trials (RCTs) are typically designed to determine beneficial intervention effects. In addition, an important aspect of every trial is to collect data on any potential harmful effects, with the aim of ensuring that the benefit-risk balance is appropriate. The language used by trialists to describe these potential harmful effects is inconsistent. In pharmacological trials, researchers collect adverse events; when a causal relationship is suspected adverse events are further classified as adverse reactions. Academic researchers have moved to collectively refer to these as harm outcomes; the pharmaceutical industry refer to these events as safety outcomes. In trials of complex interventions, phrases such as unintended consequences or effects are used. With the inconsistent use of terminology by researchers and the potential benefits to be gained from harmonising communications, we sought public opinion on terminology used to describe harmful effects and how these outcomes are communicated in the scientific literature, as well as in public facing material on medications.MethodsWe held two in-person public involvement meetings with public partners, in London and Aberdeen in 2023. Both meetings followed a pre-specified format. We provided a background to the topic including the information researchers collect on potential harms in clinical trials and shared examples on how this information gets presented in practice. We then discussed public partners’ perspectives on terminology used and communication of intervention harm in academic journals and in public facing materials. A summary of these discussions and the main topics raised by public partners are presented.ResultsPublic partners endorsed the use of different terms for different situations, preferring the use of ‘side-effect’ across all contexts and reserving the use of ‘harm’ to indicate more severe events. Generally, public partners were happy with the type of information presented in public facing materials but discussions revealed that presentation of information on public NHS websites led to misconceptions about harm.ConclusionThis work provides a starting point on preferred terminology by patients and the public to describe potential harmful intervention effects. Whilst researchers have tried to seek agreement, public partners endorsed use of different terms for different situations. We highlight some key areas for improvement in public facing materials that are necessary to avoid miscommunication and incorrect perception of harm.

Abstract TMP45: Assessing Adaptations of a Complex Secondary Stroke Prevention Intervention

Introduction: S econdary stroke prevention by U niting C ommunity and C hronic care model teams E arly to E nd D isparities (SUCCEED) was a randomized trial of a multilevel complex intervention to enhance risk factor control after stroke. Subjects randomized to intervention were managed by an advanced practice clinician (APC)-community health worker (CHW) team. Within the framework of ≥3 clinic and ≥3 home visits, and Chronic Disease Self-Management Program (CDSMP) workshops, the team tailored the intervention to meet participants’ needs. To describe how the intervention was implemented and adapted, we used the form/function framework. Methods: We identified key domains (overall goals of intervention), motivating needs (importance of targeting each domain), functions (methods for addressing motivating needs), and forms (tools, resources, methods for accomplishing each function). Two study leaders conducted semi-structured interviews with 4 APCs and 4 CHWs to identify forms used. APCs and CHWs described how frequently they used each form and usefulness via a RedCap survey. Descriptive statistics were subsequently run with R version 4.2.3. Results: SUCCEED targeted 7 domains: medication adherence, stroke literacy, self-management skills, care coordination, healthcare system navigation, social support, and addressing barriers. Each domain had 1-7 motivating needs and 4-13 functions. Each function had 5-23 forms, resulting in a total of 365 forms for addressing all domains. Most providers (85%) reviewed medication bottles to assess medication adherence, strongly agreeing this was useful. Pill organizers and stickers were used 53% of the time to ensure patients knew what medications they should be taking; 71% strongly agreed this was useful. Providers identified physical/environmental/social/literacy barriers during both home visits and CDSMP workshops (71%); all providers found this combination helpful. Conclusion: The form/function framework is useful for describing real-world adaptations of complex interventions. We identified key aspects of the intervention that providers used frequently and found useful, to inform future development of secondary stroke prevention interventions.

Abstract HUP9: Assessing Adaptations of a Complex Secondary Stroke Prevention Intervention

Introduction: S econdary stroke prevention by U niting C ommunity and C hronic care model teams E arly to E nd D isparities (SUCCEED) was a randomized trial of a multilevel complex intervention to enhance risk factor control after stroke. Subjects randomized to intervention were managed by an advanced practice clinician (APC)-community health worker (CHW) team. Within the framework of ≥3 clinic and ≥3 home visits, and Chronic Disease Self-Management Program (CDSMP) workshops, the team tailored the intervention to meet participants’ needs. To describe how the intervention was implemented and adapted, we used the form/function framework. Methods: We identified key domains (overall goals of intervention), motivating needs (importance of targeting each domain), functions (methods for addressing motivating needs), and forms (tools, resources, methods for accomplishing each function). Two study leaders conducted semi-structured interviews with 4 APCs and 4 CHWs to identify forms used. APCs and CHWs described how frequently they used each form and usefulness via a RedCap survey. Descriptive statistics were subsequently run with R version 4.2.3. Results: SUCCEED targeted 7 domains: medication adherence, stroke literacy, self-management skills, care coordination, healthcare system navigation, social support, and addressing barriers. Each domain had 1-7 motivating needs and 4-13 functions. Each function had 5-23 forms, resulting in a total of 365 forms for addressing all domains. Most providers (85%) reviewed medication bottles to assess medication adherence, strongly agreeing this was useful. Pill organizers and stickers were used 53% of the time to ensure patients knew what medications they should be taking; 71% strongly agreed this was useful. Providers identified physical/environmental/social/literacy barriers during both home visits and CDSMP workshops (71%); all providers found this combination helpful. Conclusion: The form/function framework is useful for describing real-world adaptations of complex interventions. We identified key aspects of the intervention that providers used frequently and found useful, to inform future development of secondary stroke prevention interventions.

Protocol for the development and validation of a patient reported measure (PRM) of treatment burden in stroke.

Treatment burden is the workload of healthcare for people with long-term conditions and the impact on wellbeing. A validated measure of treatment burden after stroke is needed. We aim to adapt a patient-reported measure (PRM) of treatment burden in multimorbidity, PETS (Patient Experience with Treatment and Self-Management version 2.0), to create a stroke-specific measure, PETS-stroke. We aim to examine content validity, construct validity, reliability and feasibility in a stroke survivor population. 1) Adaptation of 60-item PETS to PETS-stroke using a taxonomy of treatment burden. 2) Content validity testing through cognitive interviews that will explore the importance, relevance and clarity of each item. 3) Evaluation of scale psychometric properties through analysis of data from stroke survivors recruited via postal survey (n=340). Factor structure will be tested with confirmatory factor analysis and Cronbach's alpha will be used to index internal consistency. Construct validity will be tested against: The Stroke Southampton Self-Management Questionnaire; The Satisfaction with Stroke Care Measure; and The Shortened Stroke Impact Scale. We will explore known-groups validity by exploring the association between treatment burden, socioeconomic deprivation and multimorbidity. Test-retest reliability will be examined via re-administration after 2 weeks. Acceptability and feasibility of use will be explored via missing data rates and telephone interviews with 30 participants. We aim to create a validated PRM of treatment burden after stroke. PETS-stroke is designed for use as an outcome measure in clinical trials of stroke treatments and complex interventions to ascertain if treatments are workable for patients in the context of their everyday lives.

Evidence Synthesis for Complex Interventions Using Meta-Regression Models.

A goal of evidence synthesis for trials of complex interventions is to inform the design or implementation of novel versions of complex interventions by predicting expected outcomes with each intervention version. Conventional aggregate data meta-analyses of studies comparing complex interventions have limited ability to provide such information. We argue that evidence synthesis for trials of complex interventions should forgo aspirations of estimating causal effects and instead model the response surface of study results to 1) summarize the available evidence and 2) predict the average outcomes of future studies or in new settings. We illustrate this modeling approach using data from a systematic review of diabetes quality improvement (QI) interventions involving at least 1 of 12 QI strategy components. We specify a series of meta-regression models to assess the association of specific components with the posttreatment outcome mean and compare the results to conventional meta-analysis approaches. Compared with conventional approaches, modeling the response surface of study results can better reflect the associations between intervention components and study characteristics with the posttreatment outcome mean. Modeling study results using a response surface approach offers a useful and feasible goal for evidence synthesis of complex interventions that rely on aggregate data.

1600 COMMUNITY-BASED COMPLEX INTERVENTIONS TO SUSTAIN INDEPENDENCE IN OLDER PEOPLE: SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

Abstract Introduction Sustaining independence is important for older people, but there is insufficient guidance about which community services to implement. Methods Systematic review and network meta-analysis (NMA; PROSPERO CRD42019162195) to synthesise effectiveness evidence from randomised or cluster-randomised controlled trials of community-based complex interventions to sustain independence for older people (mean age 65+) living at home, grouped according to their intervention components. Main outcomes: Living at home, activities of daily living (ADL), care-home placement, and service/economic outcomes at one year. We searched five databases and two registries, and scanned reference lists. A random-effects NMA was used. We assessed risk of bias, inconsistency, and certainty of evidence. Results We included 129 studies (74,946 participants). Nineteen intervention components, including ‘multifactorial-action’ (individualised care planning), were identified in 63 combinations. Few studies contributed to each comparison. High risk of bias and imprecision meant results were very low certainty (not reported) or low certainty (unless otherwise stated). Findings may not apply to all contexts. For living at home, evidence favoured ‘multifactorial-action and review with medication-review’ (odds ratio (OR) 1.22, 95% CI 0.93 to 1.59; moderate certainty), and three other interventions: ‘multifactorial-action with medication-review’; ‘cognitive training, medication-review, nutrition and exercise’; and ‘ADL, nutrition and exercise’. Four interventions may reduce odds of remaining at home. For instrumental ADL (IADL), evidence favoured ‘multifactorial-action and review with medication-review’ (standardised mean difference (SMD) 0.11, 95% CI 0.00 to 0.21; moderate certainty). Two interventions may reduce IADL. For personal ADL, evidence favoured ‘exercise, multifactorial-action and review with medication-review and self-management’ (SMD 0.16, 95% CI -0.51 to 0.82). Among homecare recipients, evidence favoured addition of multifactorial-action and review with medication-review (SMD 0.60, 95% CI 0.32 to 0.88). Other findings were inconclusive. Conclusions The intervention combinations most likely to sustain independence include multifactorial-action, medication-review and ongoing review of patients. Unexpectedly, some combinations may reduce independence.

Protocol for the development and validation of a patient reported measure (PRM) of treatment burden in stroke

Background Treatment burden is the workload of healthcare for people with long-term conditions and the impact on wellbeing. A validated measure of treatment burden after stroke is needed. We aim to adapt a patient-reported measure (PRM) of treatment burden in multimorbidity, PETS (Patient Experience with Treatment and Self-Management version 2.0), to create a stroke-specific measure, PETS-stroke. We aim to examine content validity, construct validity, reliability and feasibility in a stroke survivor population. Methods 1) Adaptation of 60-item PETS to PETS-stroke using a taxonomy of treatment burden. 2) Content validity testing through cognitive interviews that will explore the importance, relevance and clarity of each item. 3) Evaluation of scale psychometric properties through analysis of data from stroke survivors recruited via postal survey (n=340). Factor structure will be tested with confirmatory factor analysis and Cronbach’s alpha will be used to index internal consistency. Construct validity will be tested against: The Stroke Southampton Self-Management Questionnaire; The Satisfaction with Stroke Care Measure; and The Shortened Stroke Impact Scale. We will explore known-groups validity by exploring the association between treatment burden, socioeconomic deprivation and multimorbidity. Test-retest reliability will be examined via re-administration after 2 weeks. Acceptability and feasibility of use will be explored via missing data rates and telephone interviews with 30 participants. Conclusions We aim to create a validated PRM of treatment burden after stroke. PETS-stroke is designed for use as an outcome measure in clinical trials of stroke treatments and complex interventions to ascertain if treatments are workable for patients in the context of their everyday lives.

“What I wanted to do was build myself back up and prepare”: qualitative findings from the PERCEPT trial of prehabilitation during autologous stem cell transplantation in myeloma

BackgroundThe addition of qualitative methodology to randomised controlled trials evaluating complex interventions allows better understanding of contextualised factors and their potential influence on trial delivery and outcomes, as well as opportunities for feedback on trial participation to improve future trial protocols. This study explored the experiences of participation in cancer rehabilitation research during active cancer treatment. Participants were people living with haematological cancer myeloma, undergoing autologous stem cell transplantation (ASCT) recruited to the PERCEPT myeloma pilot trial.MethodsA qualitative semi-structured interview study, embedded within a pilot randomised controlled trial of a physiotherapist-led exercise intervention delivered before, during and after ASCT among people living with myeloma. Transcripts were analysed using reflexive thematic analysis.ResultsInterviews from 16 trial participants (n = 8 intervention group; n = 8 control group; mean age 61 years, 56% male) were analysed. Four main themes were identified: (1) “It’s not just beneficial for me, it’s for people after me as well”; (2) Disparities in experience of recovery – expectations, feeling prepared and support; (3) “What I wanted to do was build myself back up and prepare”; (4) Active ingredients – participants’ experience of the trial intervention. Participants reported both altruistic and perceived personal gain as motivators for enrolling in the trial. Disappointment caused by allocation to control arm may have led to participants seeking exercise elsewhere, indicating possible contamination of control condition. Disparities in experience of recovery from transplant were evident with intervention participants reporting greater trajectory of recovery.ConclusionsThe findings from this embedded qualitative study highlight numerous considerations required when designing pilot and efficacy trials of complex interventions. The addition of qualitative investigation offers greater understanding of motivations for participation, intervention mechanisms at play as well as effects of participation that may impact interpretation of quantitative outcomes.Trial registrationQualitative findings from a prospectively registered pilot trial (ISRCTN15875290), registered 13/02/2019.

Integrated Short-term Palliative Rehabilitation to improve quality of life and equitable care access in incurable cancer (INSPIRE): a multinational European research project.

Disability related to incurable cancer affects over a million Europeans each year and people with cancer rank loss of function among the most common unmet supportive care needs. To test the clinical and cost-effectiveness of an integrated short-term palliative rehabilitation intervention, to optimise function and quality of life in people affected by incurable cancer. This is a multinational, parallel group, randomised, controlled, assessor blind, superiority trial. The INSPIRE consortium brings together leaders in palliative care, oncology and rehabilitation from partner organisations across Europe, with complementary expertise in health service research, trials of complex interventions, mixed-method evaluations, statistics and economics. Partnership with leading European civil society organisations ensures citizen engagement and dissemination at the highest level. We will conduct a multinational randomised controlled trial across five European countries, recruiting participants to assess the effectiveness of palliative rehabilitation for people with incurable cancer on the primary outcome - quality of life - and secondary outcomes including disability, symptom burden and goal attainment. To support trial conduct and enhance analysis of trial data, we will also conduct: comparative analysis of current integration of rehabilitation across oncology and palliative care services; mixed-method evaluations of equity and inclusivity, processes and implementation for the intervention, at patient, health service and health system levels. Finally, we will conduct an evidence synthesis, incorporating INSPIRE findings, and a Delphi consensus to develop an international framework for palliative rehabilitation practice and policy, incorporating indicators, core interventions, outcomes and integration methods. If positive, the trial could produce a scalable and equitable intervention to improve function and quality of life in people with incurable cancer and reduce the burden of care for their families. It could also upskill the practitioners involved and motivate future research questions. The intervention could be adapted and integrated into different health systems using existing staff and services, with little or no additional cost.

Stakeholder perspectives of a pilot multicomponent delirium prevention intervention for adult patients with advanced cancer in palliative care units: A behaviour change theory-based qualitative study

Background: Theory-based and qualitative evaluations in pilot trials of complex clinical interventions help to understand quantitative results, as well as inform the feasibility and design of subsequent effectiveness and implementation trials. Aim: To explore patient, family, clinician and volunteer (‘stakeholder’) perspectives of the feasibility and acceptability of a multicomponent non-pharmacological delirium prevention intervention for adult patients with advanced cancer in four Australian palliative care units that participated in a phase II trial, the ‘PRESERVE pilot study’. Design: A trial-embedded qualitative study via semi-structured interviews and directed content analysis using Michie’s Behaviour Change Wheel and the Theoretical Domains Framework. Setting/participants: Thirty-nine people involved in the trial: nurses (n = 17), physicians (n = 6), patients (n = 6), family caregivers (n = 4), physiotherapists (n = 3), a social worker, a pastoral care worker and a volunteer. Results: Participants’ perspectives aligned with the ‘capability’, ‘opportunity’ and ‘motivation’ domains of the applied frameworks. Of seven themes, three were around the alignment of the delirium prevention intervention with palliative care (intervention was considered routine care; intervention aligned with the compassionate and collaborative culture of palliative care; and differing views of palliative care priorities influenced perspectives of the intervention) and four were about study processes more directly related to adherence to the intervention (shared knowledge increased engagement with the intervention; impact of the intervention checklist on attention, delivery and documentation of the delirium prevention strategies; clinical roles and responsibilities; and addressing environmental barriers to delirium prevention). Conclusion: This theory-informed qualitative study identified multiple influences on the delivery and documentation of a pilot multicomponent non-pharmacological delirium prevention intervention in four palliative care units. Findings inform future definitive studies of delirium prevention in palliative care. Australian New Zealand Clinical Trials Registry, ACTRN12617001070325; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373168

Treatment fidelity monitoring, reporting and findings in a complex aphasia intervention trial: a substudy of the Very Early Rehabilitation in SpEech (VERSE) trial

BackgroundTreatment fidelity is inconsistently reported in aphasia research, contributing to uncertainty about the effectiveness of types of aphasia therapy following stroke. We outline the processes and outcomes of treatment fidelity monitoring in a pre-specified secondary analysis of the VERSE trial.MethodsVERSE was a 3-arm, single-blinded RCT with a 12-week primary endpoint comparing Usual Care (UC) to two higher intensity treatments: Usual Care-Plus (UC-Plus) and VERSE, a prescribed intervention. Primary outcome results were previously reported. This secondary analysis focused on treatment fidelity. Video-recorded treatment sessions in the higher intensity study arms were evaluated for treatment adherence and treatment differentiation. Treatment components were evaluated using a pre-determined fidelity checklist. Primary outcome: prescribed amount of therapy time (minutes); secondary outcomes: (i) adherence to therapy protocol (%) and (ii) treatment differentiation between control and high intensity groups.ResultsTwo hundred forty-six participants were randomised to Usual Care (n=81), Usual Care-Plus (n=82), and VERSE (n=83). One hundred thirty-five (82%) participants in higher intensity intervention arms received the minimum prescribed therapy minutes. From 10,805 (UC 7787; UC-Plus 1450; VERSE 1568) service events, 431 treatment protocol deviations were noted in 114 participants. Four hundred thirty-seven videos were evaluated. The VERSE therapists achieved over 84% adherence to key protocol elements. Higher stroke and aphasia severity, older age, and being in the UC-Plus group predicted more treatment deviations.ConclusionsWe found high levels of treatment adherence and differentiation between the intervention arms, providing greater confidence interpreting our results. The comprehensive systems for intervention fidelity monitoring and reporting in this trial make an important contribution to aphasia research and, we argue, should set a new standard for future aphasia studies.Trial registrationACTRN 12613000776707

Enhancing and assessing fidelity in the TANDEM (Tailored intervention for ANxiety and DEpression Management in COPD) trial: development of methods and recommendations for research design

BackgroundDevelopment of complex interventions for management of chronic conditions has become increasingly common, with guidance now provided. Fidelity (whether the intervention is designed, delivered and received as intended) is critical to understanding if, and how an intervention works (or not). However, methods for achieving this are still evolving. This study describes the methods used in the TANDEM trial – a large multicentre study evaluating the impact of a cognitive behavioural intervention preceding routine pulmonary rehabilitation for people with chronic obstructive pulmonary disease and anxiety and or depression. Results for enhancement and training aspects of fidelity, are presented.MethodsUsing the National Institute for Health Behaviour Change Consortium (NIH BCC) framework of fidelity, a set of enhancement strategies and a fidelity measurement strategy were developed with input from a multidisciplinary team. The Cognitive First Aid Rating Scale (CFARS) was used to assess Facilitator (the respiratory professional delivering TANDEM) therapeutic competence at the end of the initial training and throughout treatment delivery (on a randomly selected set of cases). A TANDEM specific treatment adherence measure was developed following previously recommended procedures. Together these (the CFARS and adherence measure) comprised the TANDEM treatment delivery fidelity tool.ResultsHiring of respiratory professionals to the initial training programme was successful, with 44% of those expressing initial interest in being a Facilitator successfully completing the process. Video recordings of potential Facilitators conducting standardized patient role plays at the end of the initial training demonstrated fidelity of training.ConclusionsAddressing fidelity in complex intervention trials is a time and resource intensive process but has significant potential to increase understanding of results and strengthen the evidence base for effective interventions. By defining a full fidelity assessment method prior to analysis we aimed to minimise bias when interpreting results.Trial registrationISRCTN59537391. Registered on 20 March 2017. Trial protocol version 6.0, 22 April 2018. Process evaluation protocol version 4.0, 1 November 2020.

Conducting Randomized Controlled Trials of Complex Interventions in Prisons: A Sisyphean Task?

Randomized Controlled Trials (RCT) are the “gold standard” for measuring the effectiveness of an intervention. However, they have their limitations and are especially complex in prison settings. Several systematic reviews have highlighted some of the issues, including, institutional constraints e.g., “lock-downs,” follow-ups, contamination of allocation conditions and a reliance on self-report measures. In this article, we reflect on our experiences and will describe two RCTs. People in prison are a significantly disadvantaged and vulnerable group, ensuring equitable and effective interventions is key to reducing inequality and promoting positive outcomes. We ask are RCTs of complex interventions in prisons a sisyphean task? We certainly don't think so, but we propose that current accepted practice and research designs may be limiting our understanding and ability to test complex interventions in the real-world context of prisons. RCTs will always have their place, but designs need to be flexible and adaptive, with the development of other rigorous methods for evaluating impact of interventions e.g., non-randomized studies, including pre-post implementation studies. With robust research we can deliver quality evidence-based healthcare in prisons – after all the degree of civilization in a society is revealed by entering its prisons.

Perceived study-induced influence on the control group in a randomized controlled trial evaluating a complex intervention to promote psychosocial well-being after stroke: a process evaluation

BackgroundA commonly applied control condition in trials evaluating complex interventions in rehabilitation research is “usual care.” The main challenge is to ensure that the control group receives genuine usual care as delivered in everyday clinical practice. The assessment interviews and dialogues with the data collectors may influence the control group participants’ reflections on their condition and adjustments. This represents a threat to the internal validity of the trial. Thus, the aim of this study was to explore the perceived study-induced influence of assessment interviews on the adjustment of the members of a control group in a randomized clinical trial. The aim of the trial was to test a dialogue-based psychosocial intervention aiming at promoting the psychosocial well-being and adjustment of stroke survivors.MethodsFifteen participants in the control group of a multicenter stroke rehabilitation trial participated in narrative semi-structured interviews. Ricoeur’s interpretation theory guided the analysis.ResultsThe perceived study-induced influence of the assessment interviews on the adjustment process of members of the control group varied considerably. The results demonstrated that the assessment interviews facilitated some participants’ feelings of control and their ability to cope. Other participants’ statements indicate that they relied on their existing personal capacity to cope and adjust and that the assessment interviews did not make any difference either on their coping ability or on their process of adjustment.Five themes were identified that described the perceived study-induced influence of the assessment interviews in the control group. The themes illustrated that the assessments served as a safety net, enhanced awareness and understanding, encouraged seeking support, allowed the opportunity to vent disappointment, or did not make any difference either way.ConclusionsRCT assessment interviews may influence the adjustment process and represent a serious problem in measuring interventions over time in trials of complex interventions in rehabilitation research. To uphold rigor and stringency, the usual care control conditions should be thoroughly assessed and described. Informing participants only about the treatment they were allocated to receive might counteract the potential to dilute the difference between the two arms of the trial.Trial registrationClinicalTrials.gov NCT02338869. Registered on October 4, 2014

The implementation of Journeying through Dementia: Strategies to run a successful pragmatic multicenter trial of a complex intervention.

ObjectiveA key challenge in delivering pragmatic trials of complex interventions is effective implementation within the study period and beyond. We describe a trial of an intervention to improve quality of life in mild dementia (Journeying through Dementia), describe some of the challenges raised in terms of implementation, and illustrate the methods used to ensure effective implementation.MethodThe intervention was delivered by staff within local services and supervised by more experienced clinicians within those services in order to test the intervention in real‐world settings and establish the potential for future embedding into practice. Researchers delivered training sessions for all facilitators and supervisors, met at regular intervals with intervention supervisors, and provided feedback on summaries of intervention sessions created by facilitators. We conducted a thematic analysis of the content of meetings and written correspondence between the researchers and intervention supervisors regarding implementation issues.ResultsKey themes relating to difficulties with implementation were: staff absences and staff leaving posts; participant lack of engagement with intervention; difficulties with delivery of supervision; difficult group dynamics; lack of time to deliver the intervention; and lack of adherence to the intervention and its ethos.ConclusionWe provide guidance for researchers involved in the trialing of other complex interventions in how these challenges might be overcome. These include: recruiting additional staff to deliver the intervention; having clear protocols in place for managing staff absences; using supervision to problem solve participant attendance at intervention sessions and difficult group dynamics; monitoring staff engagement in supervision and addressing problems with engagement with staff and managers when this occurs; giving staff ring‐fenced time to deliver the intervention and engage in supervision; and regular monitoring and feedback in relation to the content of the intervention to ensure that it is consistent with ethos and content of the intervention manual.

Bayesian design and analysis of external pilot trials for complex interventions.

External pilot trials of complex interventions are used to help determine if and how a confirmatory trial should be undertaken, providing estimates of parameters such as recruitment, retention, and adherence rates. The decision to progress to the confirmatory trial is typically made by comparing these estimates to pre-specified thresholds known as progression criteria, although the statistical properties of such decision rules are rarely assessed. Such assessment is complicated by several methodological challenges, including the simultaneous evaluation of multiple endpoints, complex multi-level models, small sample sizes, and uncertainty in nuisance parameters. In response to these challenges, we describe a Bayesian approach to the design and analysis of external pilot trials. We show how progression decisions can be made by minimizing the expected value of a loss function, defined over the whole parameter space to allow for preferences and trade-offs between multiple parameters to be articulated and used in the decision-making process. The assessment of preferences is kept feasible by using a piecewise constant parametrization of the loss function, the parameters of which are chosen at the design stage to lead to desirable operating characteristics. We describe a flexible, yet computationally intensive, nested Monte Carlo algorithm for estimating operating characteristics. The method is used to revisit the design of an external pilot trial of a complex intervention designed to increase the physical activity of care home residents.

Integrating a brief alcohol intervention with tobacco addiction treatment in primary care: qualitative study of health care practitioner perceptions

BackgroundRandomized trials of complex interventions are increasingly including qualitative components to further understand factors that contribute to their success. In this paper, we explore the experiences of health care practitioners in a province wide smoking cessation program (the Smoking Treatment for Ontario Patients program) who participated in the COMBAT trial. This trial examined if the addition of an electronic prompt embedded in a Clinical Decision Support System (CDSS)—designed to prompt practitioners to Screen, provide a Brief intervention and Referral to Treatment (SBIRT) to patients who drank alcohol above the amounts recommended by the Canadian Cancer Society guidelines—influenced the proportion of practitioners delivering a brief intervention to their eligible patients. We wanted to understand the factors influencing implementation and acceptability of delivering a brief alcohol intervention for treatment-seeking smokers for health care providers who had access to the CDSS (intervention arm) and those who did not (control arm).MethodsTwenty-three health care practitioners were selected for a qualitative interview using stratified purposeful sampling (12 from the control arm and 11 from the intervention arm). Interviews were 45 to 90 min in length and conducted by phone using an interview guide that was informed by the National Implementation Research Network’s Hexagon tool. Interview recordings were transcribed and coded iteratively between three researchers to achieve consensus on emerging themes. The preliminary coding structure was developed using the National Implementation Research Network’s Hexagon Tool framework and data was analyzed using the framework analysis approach.ResultsSeventy eight percent (18/23) of the health care practitioners interviewed recognized the need to simultaneously address alcohol and tobacco use. Seventy four percent (17/23), were knowledgeable about the evidence of health risks associated with dual alcohol and tobacco use but 57% (13/23) expressed concerns with using the Canadian Cancer Society guidelines to screen for alcohol use. Practitioners acknowledged the value of adding a validated screening tool to the STOP program’s baseline questionnaire (19/23); however, following through with a brief intervention and referral to treatment proved challenging due to lack of training, limited time, and fear of stigmatizing patients. Practitioners in the intervention arm (5/11; 45%) might not follow the recommendations from CDSS if these recommendations are not perceived as beneficial to the patients.ConclusionsThe results of the study show that practitioners’ beliefs were reflective of the current social norms around alcohol use and this influenced their decision to offer a brief alcohol intervention. Future interventions need to emphasize both organizational and sociocultural factors as part of the design. The results of this study point to the need to change social norms regarding alcohol in order to effectively implement interventions that target both alcohol and tobacco use in primary care clinics.Trial registration ClinicalTrials.gov NCT03108144. Retrospectively registered 11 April 2017, https://www.clinicaltrials.gov/ct2/show/NCT03108144