A new design for pragmatic randomised controlled trials: a 'Patient Cohort' RCT of treatment by a homeopath for menopausal hot flushes

There is debate regarding the effectiveness of homeopathy and its continuing provision in the NHS, and despite 150+ clinical trials there are conflicting opinions as to what can be concluded from these trials. This thesis addresses the question: “What type of clinical trial design can provide the information needed to make decisions about the provision of homeopathy in a publicly funded healthcare system?” A critique of the methods used in existing clinical trial designs was undertaken which identified twelve key criteria for appropriate clinical trial design; methods from existing standard and alternative clinical trial designs were adapted in order to derive a new clinical trial design that has the potential to meet all twelve key criteria (the ‘Patient Cohort’ RCT design). A current clinical question was identified: ‘What is the clinical & cost effectiveness of treatment by a homeopath for women with menopausal hot flushes?” and a population based survey confirmed the importance of this question. The ‘Patient Cohort’ RCT design was piloted in an NHS setting in order to address this current clinical question. Seventy ‘with need’ women were recruited to the Hot Flush Cohort of whom forty-eight were eligible for the treatment, a proportion of whom were randomly selected to be offered the treatment. 70.8% of those offered treatment accepted the offer and completion of outcome measures was high (93.7%). The results indicate that a full trial of this treatment for this condition may be worthwhile conducting. A full RCT using this design would be an appropriate clinical trial design to provide answers as to the provision of homeopathy and other clinician delivered interventions in publicly funded healthcare system such as the NHS. The ‘Patient Cohort’ RCT design can be usefully applied to clinical questions that require very pragmatic approaches yet need the scientific rigour of randomisation

Valuing Breastfeeding: Health Care Professionals’ Experiences of Delivering a Conditional Cash Transfer Scheme for Breastfeeding in Areas With Low Breastfeeding Rates

Alongside a randomized controlled trial testing the effectiveness of offering a cash transfer scheme (shopping vouchers) to mothers in areas with low breastfeeding rates, qualitative interviews were conducted with health care professionals delivering the scheme to explore their experiences. Health care professionals (n = 34; mainly midwives and health visitors) were interviewed in depth. Transcripts from recorded interviews were analyzed using a Framework Analysis approach. There was widespread acceptance of the scheme by health care professionals, with prior concerns regarding bribery and coercion being quickly allayed. Health care professionals reported that the scheme fitted in well with their routine ways of promoting and endorsing breastfeeding. They described their experiences of women’s positive reaction toward the scheme and how the scheme encouraged breastfeeding and gave breastfeeding higher value. Health care professionals reported that the incentives helped them engage women and promote and support breastfeeding in areas with low breastfeeding rates

Development of a conceptual framework for defining trial efficiency

BackgroundGlobally, there is a growing focus on efficient trials, yet numerous interpretations have emerged, suggesting a significant heterogeneity in understanding “efficiency” within the trial context. Therefore in this study, we aimed to dissect the multifaceted nature of trial efficiency by establishing a comprehensive conceptual framework for its definition.ObjectivesTo collate diverse perspectives regarding trial efficiency and to achieve consensus on a conceptual framework for defining trial efficiency.MethodsFrom July 2022 to July 2023, we undertook a literature review to identify various terms that have been used to define trial efficiency. We then conducted a modified e-Delphi study, comprising an exploratory open round and a subsequent scoring round to refine and validate the identified items. We recruited a wide range of experts in the global trial community including trialists, funders, sponsors, journal editors and members of the public. Consensus was defined as items rated “without disagreement”, measured by the inter-percentile range adjusted for symmetry through the UCLA/RAND approach.Results Seventy-eight studies were identified from a literature review, from which we extracted nine terms related to trial efficiency. We then used review findings as exemplars in the Delphi open round. Forty-nine international experts were recruited to the e-Delphi panel. Open round responses resulted in the refinement of the initial nine terms, which were consequently included in the scoring round. We obtained consensus on all nine items: 1) four constructs that collectively define trial efficiency containing scientific efficiency, operational efficiency, statistical efficiency and economic efficiency; and 2) five essential building blocks for efficient trial comprising trial design, trial process, infrastructure, superstructure, and stakeholders.ConclusionsThis is the first attempt to dissect the concept of trial efficiency into theoretical constructs. Having an agreed definition will allow better trial implementation and facilitate effective communication and decision-making across stakeholders. We also identified essential building blocks that are the cornerstones of an efficient trial. In this pursuit of understanding, we are not only unravelling the complexities of trial efficiency but also laying the groundwork for evaluating the efficiency of an individual trial or a trial system in the future.<br/

Ethics and practice of trials within cohorts: An emerging pragmatic trial design

BACKGROUND: With increasing emphasis on pragmatic trials, new randomized clinical trial designs are being proposed to enhance the "real world" nature of the data generated. We describe one such design, appropriate for unmasked pragmatic clinical trials in which the control arm receives usual care, called "Trials within Cohorts" that is increasingly used in various countries because of its efficiency in recruitment, advantages in reducing subject burden, and ability to better mimic real-world consent processes. METHODS: Descriptive, ethical, and US regulatory analysis of the Trials within Cohorts design. RESULTS: Trials within Cohorts design involves, after recruitment into a cohort, randomization of eligible subjects, followed by an asymmetric treatment of the two arms: those selected for the experimental arm provide informed consent for the intervention trial, while the data from the control arm are used based on prior broad permission. Thus, unlike the traditional Zelen post-randomization consent design, the cohort participants are informed about future research within the cohort; however, the extent of this disclosure currently varies among studies. Thus, ethical analysis is provided for two types of situations: when the pre-randomization disclosure and consent regarding the embedded trials are fairly explicit and detailed versus when they consist of only general statements about future data use. These differing ethical situations could have implications for how ethics review committees apply US research rules regarding waivers and alterations of informed consent. CONCLUSION: Trials within Cohorts is a promising new pragmatic randomized controlled trial design that is being increasingly used in various countries. Although the asymmetric consent procedures for the experimental versus control arm subjects can initially raise ethical concerns, it is ethically superior to previous post-randomization consent designs and can have important advantages over traditional trial designs

Deprivation, clubs and drugs: results of a UK regional population-based cross-sectional study of weight management strategies

Background Despite rising levels of obesity in England, little is known about slimming club and weight loss drug (medication) use or users. In order to inform future commissioning, we report the prevalence of various weight management strategies and examine the associations between slimming club and medication use and age, gender, deprivation and body mass index. Methods A population based cross-sectional survey of 26,113 adults was conducted in South Yorkshire using a self-completed health questionnaire. Participants were asked whether they had ever used the following interventions to manage their weight: increasing exercise, healthy eating, controlling portion size, slimming club, over the counter weight loss medication, or meal replacements. Factors associated with slimming club and weight-loss medication use were explored using logistic regression. Results Over half of the sample was either overweight (36.6%) or obese (19.6%). Obesity was more common in the most deprived areas compared to the least deprived (26.3% vs. 12.0%). Healthy eating (49.0%), controlling portion size (43.4%), and increasing exercise (43.0%) were the most commonly reported weight management strategies. Less common strategies were attending a slimming club (17.2%), meal replacements (3.4%) and weight-loss medication (3.2%). Adjusting for BMI, age, deprivation and long standing health conditions, women were significantly more likely to report ever using a slimming club (adjusted OR = 18.63, 95% CI = 16.52–21.00) and more likely to report ever using over the counter weight-loss medications (AOR = 3.73, 95% CI = 3.10-4.48), while respondents from the most deprived areas were less likely to report using slimming clubs (AOR = 0.60, 95% CI = 0.53-0.68), and more likely to reporting using weight loss medications (AOR =1.38, 95% CI = 1.05-1.82). Conclusion A large proportion of individuals report having used weight management strategies. Slimming clubs and over-the-counter weight loss medication account for a smaller proportion of the overall uptake. Those from less deprived areas were more likely to use slimming clubs while those from more deprived areas were more likely to use weight-loss medications. Future NHS and Local Authority commissioning of weight management services must be aware of this varying social gradient in weight management strategies

Depressed patients’ experiences with and perspectives on treatment provided by homeopaths. A qualitative interview study embedded in a trial

Introduction Depression is one of the clinical conditions patients most commonly consult homeopaths. This study therefore aimed to learn about patients’ experiences having this intervention. Methods A semi-structured qualitative interview study was nested within a randomised controlled trial to learn about depressed patients’ experiences with treatment provided by homeopaths. A purposive selection of adults with moderate to severe self-reported depression were included. Interviews were conducted post initial consultation and six months post-randomisation. Thematic analysis was used to develop themes describing participants’ experiences, thoughts and understandings. Results Forty-six interviews were carried out with 33 adults. Sixteen themes were developed and have been categorised under three main headings: 1) changed understanding of the intervention, with themes such as understanding the intervention as being adapted; 2) experiences with the consultation and the medication, such as caring support, trust and optimism arising from consultations with homeopaths; and 3) changes in state of health, such as improvement in mood, wellbeing and ability to cope, or little or no change, or transient adverse events. Conclusion This is the first qualitative study of depressed patients’ experiences with treatment provided by homeopaths. Results provide an insight into their experiences with consultations and homeopathic and antidepressant medication, their understanding of the intervention, and the changes in their state of health over time

Randomised trials conducted using cohorts : a scoping review

Acknowledgements We thank Margaret Sampson, MLIS, PhD, AHIP (Children’s Hospital of Eastern Ontario, Ottawa, Canada) for developing the search strategies on behalf of the CONSORT team. We thank Dr Philippa Fibert, St Mary’s University, Twickenham, London for her help in screening publications for inclusion.Peer reviewe

Valuing breastfeeding: a qualitative study of women's experiences of a financial incentive scheme for breastfeeding

BACKGROUND: A cluster randomised controlled trial of a financial incentive for breastfeeding conducted in areas with low breastfeeding rates in the UK reported a statistically significant increase in breastfeeding at 6-8 weeks. In this paper we report an analysis of interviews with women eligible for the scheme, exploring their experiences and perceptions of the scheme and its impact on breastfeeding to support the interpretation of the results of the trial. METHODS: Semi-structured interviews were carried out with 35 women eligible for the scheme during the feasibility and trial stages. All interviews were recorded and verbatim transcripts analysed using a Framework Analysis approach. RESULTS: Women reported that their decisions about infant feeding were influenced by the behaviours and beliefs of their family and friends, socio-cultural norms and by health and practical considerations. They were generally positive about the scheme, and felt valued for the effort involved in breastfeeding. The vouchers were frequently described as a reward, a bonus and something to look forward to, and helping women keep going with their breastfeeding. They were often perceived as compensation for the difficulties women encountered during breastfeeding. The scheme was not thought to make a difference to mothers who were strongly against breastfeeding. However, women did believe the scheme would help normalise breastfeeding, influence those who were undecided and help women to keep going with breastfeeding and reach key milestones e.g. 6 weeks or 3 months. CONCLUSIONS: The scheme was acceptable to women, who perceived it as rewarding and valuing them for breastfeeding. Women reported that the scheme could raise awareness of breastfeeding and encourage its normalisation. This provides a possible mechanism of action to explain the results of the trial. TRIAL REGISTRATION: The trial is registered with the ISRCTN registry, number 44898617 , https://www.isrctn.com

Most patients reported positively or neutrally of having served as controls in the trials within cohorts design

Objectives: To evaluate patients’ experience of having served as controls without a notification at the time of randomization in the context of the trial within cohorts (TwiCs) design. Methods: Patients were asked for their opinion on having served as controls in TwiCs, before and after having been provided the trial results. Patients had provided broad consent to randomization at cohort entry and had served as controls in one of two TwiCs (an exercise program after breast cancer treatment or radiotherapy dose-escalation for rectal cancer). Results: Two to 6 years after cohort entry, 15% (n = 16) of all patients remembered having provided broad consent to randomization. Before disclosure of trial results, 47% (n = 52) of patients thought positively, 45% (n = 50) neutrally, and 2% (n = 2) negatively of having served as controls in one of the two trials. Seventeen percent (n = 18) of patients were positive, 65% (n = 71) neutral, and 11% (n = 12) negative about not having been notified when serving as controls. The survey results were comparable after disclosure of trial results. Conclusions: These results support the use of the TwiCs design with the staged-informed consent procedure. Keeping patients engaged and aware of the consents provided might further improve patients’ experience of serving as controls in TwiCs

Prevalence of homeopathy use by the general population worldwide: a systematic review

Aim: To systematically review surveys of 12-month prevalence of homeopathy use by the general population worldwide Methods: Studies were identified via database searches to October 2015. Study quality was assessed using a six-item tool. All estimates were in the context of a survey which also reported prevalence of any complementary and alternative medicine use. Results: A total of 36 surveys were included. Of these, 67% met four of six quality criteria. Twelve-month prevalence of treatment by a homeopath was reported in 24 surveys of adults (median 1.5%, range 0.2% to 8.2%). Estimates for children were similar to those for adults. Rates in the US, UK, Australia and Canada all ranged from 0.2% to 2.9% and remained stable over the years surveyed (1986-2012). Twelve-month prevalence of all use of homeopathy (purchase of over-the-counter homeopathic medicines and treatment by a homeopath) was reported in 10 surveys of adults (median 3.9%, range 0.7% to 9.8%) while a further 11 surveys which did not define the type of homeopathy use reported similar data. Rates in the US and Australia ranged from 1.7% to 4.4% and remained stable over the years surveyed. The highest use was reported by a survey in Switzerland where homeopathy is covered by mandatory health insurance. Conclusions: This review summarises 12-month prevalence of homeopathy use from surveys conducted in eleven countries (USA, UK, Australia, Israel, Canada, Switzerland, Norway, Germany, South Korea, Japan and Singapore). Each year a small but significant percentage of these general populations use homeopathy. This includes visits to homeopaths as well as purchase of over-the-counter homeopathic medicines