Evidence for risk of bias in cluster randomised trials: review of recent trials published in three general medical journals

Objective To examine the prevalence of a risk of bias associated with the design and conduct of cluster randomised controlled trials among a sample of recently published studies.Design Retrospective review of cluster randomised trials published in the BMJ, Lancet, and New England Journal of Medicine from January 1997 to October 2002.Main outcome measures Prevalence of secure randomisation of clusters, identification of participants before randomisation (to avoid foreknowledge of allocation), differential recruitment between treatment arms, differential application of inclusion and exclusion criteria, and differential attrition.Results Of the 36 trials identified, 24 were published in the BMJ,11 in the Lancet, and a single trial in the New England Journal of Medicine. At the cluster level, 15 (42%) trials provided evidence for secure allocation and 25 (69%) used stratified allocation. Few trials showed evidence of imbalance at the cluster level. However, some evidence of susceptibility to risk of bias at the individual level existed in 14 (39%) studies.Conclusions Some recently published cluster randomised trials may not have taken adequate precautions to guard against threats to the internal validity of their design.     

Conflicts of interest at medical journals: the influence of industry-supported randomised trials on journal impact factors and revenue - cohort study

Background

Transparency in reporting of conflict of interest is an increasingly important aspect of publication in medical journals. Publication of large industry-supported trials may generate many citations and journal income through reprint sales and thereby be a source of conflicts of interest for journals. We investigated industry-supported trials'' influence on journal impact factors and revenue.

Methods and Findings

We sampled six major medical journals (Annals of Internal Medicine, Archives of Internal Medicine, BMJ, JAMA, The Lancet, and New England Journal of Medicine [NEJM]). For each journal, we identified randomised trials published in 1996–1997 and 2005–2006 using PubMed, and categorized the type of financial support. Using Web of Science, we investigated citations of industry-supported trials and the influence on journal impact factors over a ten-year period. We contacted journal editors and retrieved tax information on income from industry sources. The proportion of trials with sole industry support varied between journals, from 7% in BMJ to 32% in NEJM in 2005–2006. Industry-supported trials were more frequently cited than trials with other types of support, and omitting them from the impact factor calculation decreased journal impact factors. The decrease varied considerably between journals, with 1% for BMJ to 15% for NEJM in 2007. For the two journals disclosing data, income from the sales of reprints contributed to 3% and 41% of the total income for BMJ and The Lancet in 2005–2006.

Conclusions

Publication of industry-supported trials was associated with an increase in journal impact factors. Sales of reprints may provide a substantial income. We suggest that journals disclose financial information in the same way that they require them from their authors, so that readers can assess the potential effect of different types of papers on journals'' revenue and impact. Please see later in the article for the Editors'' Summary     

Discussing randomised clinical trials of cancer therapy: evaluation of a Cancer Research UK training programme

Objective To evaluate a training intervention aimed at improving healthcare professionals'' communication with cancer patients about randomised clinical trials.Design Before and after evaluation of training programme.Setting Members of the National Cancer Research Network, Scottish Trials Network, and the Welsh Cancer Trials NetworkParticipants 101 healthcare professionals (33 clinicians and 68 research nurses).Intervention Four modules delivered by a trained facilitator using videotapes and interactive exercises to cover general issues about discussing randomised clinical trials with patients, problems specific to adjuvant trials, trials with palliation as the goal, and trials where patients had a strong preference for one treatment arm.Main outcome measures Before and after the intervention, participants were videotaped discussing a trial with an actor portraying a patient. These consultations were assessed for presence of information required by good clinical practice guidelines. The actor patients gave an assessment after each interview. Participants reported their self confidence about key aspects of trial discussion.Results Analysis of the videotaped consultations showed that, after intervention, significantly more participants displayed key communication behaviours such as explaining randomisation (69 v 81, odds ratio 2.33, P = 0.033), checking patients'' understanding (11 v 31, odds ratio 3.22, P = 0.002), and discussing standard treatment (73 v 88, odds ratio 4.75, P = 0.005) and side effects (69 v 85, odds ratio 3.29, P = 0.006). Participants'' self confidence increased significantly (P < 0.001) across all areas. Actor patients'' ratings of participants'' communication showed significant improvements for 12/15 key items.Conclusion This intensive 8 hour intervention significantly improved participants'' confidence and competence when communicating about randomised clinical trials.     

What is meant by intention to treat analysis? Survey of published randomised controlled trials

ObjectivesTo assess the methodological quality of intention to treat analysis as reported in randomised controlled trials in four large medical journals.DesignSurvey of all reports of randomised controlled trials published in 1997 in the BMJ, Lancet, JAMA, and New England Journal of Medicine.Results119 (48%) of the reports mentioned intention to treat analysis. Of these, 12 excluded any patients who did not start the allocated intervention and three did not analyse all randomised subjects as allocated. Five reports explicitly stated that there were no deviations from random allocation. The remaining 99 reports seemed to analyse according to random allocation, but only 34 of these explicitly stated this. 89 (75%) trials had some missing data on the primary outcome variable. The methods used to deal with this were generally inadequate, potentially leading to a biased treatment effect. 29 (24%) trials had more than 10% of responses missing for the primary outcome, the methods of handling the missing responses were similar in this subset.ConclusionsThe intention to treat approach is often inadequately described and inadequately applied. Authors should explicitly describe the handling of deviations from randomised allocation and missing responses and discuss the potential effect of any missing response. Readers should critically assess the validity of reported intention to treat analyses.

Key messages

• Intention to treat gives a pragmatic estimate of the benefit of a change in treatment policy rather than of potential benefit in patients who receive treatment exactly as planned
• Full application of intention to treat is possible only when complete outcome data are available for all randomised subjects
• About half of all published reports of randomised controlled trials stated that intention to treat was used, but handling of deviations from randomised allocation varied widely
• Many trials had some missing data on the primary outcome variable, and methods used to deal with this were generally inadequate, potentially leading to bias
• Intention to treat analyses are often inadequately described and inadequately applied

     

Participant informed consent in cluster randomized trials: review

Background

The Nuremberg code defines the general ethical framework of medical research with participant consent as its cornerstone. In cluster randomized trials (CRT), obtaining participant informed consent raises logistic and methodologic concerns. First, with randomization of large clusters such as geographical areas, obtaining individual informed consent may be impossible. Second, participants in randomized clusters cannot avoid certain interventions, which implies that participant informed consent refers only to data collection, not administration of an intervention. Third, complete participant information may be a source of selection bias, which then raises methodological concerns. We assessed whether participant informed consent was required in such trials, which type of consent was required, and whether the trial was at risk of selection bias because of the very nature of participant information.

Methods and Findings

We systematically reviewed all reports of CRT published in MEDLINE in 2008 and surveyed corresponding authors regarding the nature of the informed consent and the process of participant inclusion. We identified 173 reports and obtained an answer from 113 authors (65.3%). In total, 23.7% of the reports lacked information on ethics committee approval or participant consent, 53.1% of authors declared that participant consent was for data collection only and 58.5% that the group allocation was not specified for participants. The process of recruitment (chronology of participant recruitment with regard to cluster randomization) was rarely reported, and we estimated that only 56.6% of the trials were free of potential selection bias.

Conclusions

For CRTs, the reporting of ethics committee approval and participant informed consent is less than optimal. Reports should describe whether participants consented for administration of an intervention and/or data collection. Finally, the process of participant recruitment should be fully described (namely, whether participants were informed of the allocation group before being recruited) for a better appraisal of the risk of selection bias.     

Relation between the global burden of disease and randomized clinical trials conducted in Latin America published in the five leading medical journals

Background

Since 1990 non communicable diseases and injuries account for the majority of death and disability-adjusted life years in Latin America. We analyzed the relationship between the global burden of disease and Randomized Clinical Trials (RCTs) conducted in Latin America that were published in the five leading medical journals.

Methodology/Principal Findings

We included all RCTs in humans, exclusively conducted in Latin American countries, and published in any of the following journals: Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, and New England Journal of Medicine. We described the trials and reported the number of RCTs according to the main categories of the global burden of disease. Sixty-six RCTs were identified. Communicable diseases accounted for 38 (57%) reports. Maternal, perinatal, and nutritional conditions accounted for 19 (29%) trials. Non-communicable diseases represent 48% of the global burden of disease but only 14% of reported trials. No trial addressed injuries despite its 18% contribution to the burden of disease in 2000.

Conclusions/Significance

A poor correlation between the burden of disease and RCTs publications was found. Non communicable diseases and injuries account for up to two thirds of the burden of disease in Latin America but these topics are seldom addressed in published RCTs in the selected sample of journals. Funding bodies of health research and editors should be aware of the increasing burden of non communicable diseases and injuries occurring in Latin America to ensure that this growing epidemic is not neglected in the research agenda and not affected by publication bias.     

Centre Selection for Clinical Trials and the Generalisability of Results: A Mixed Methods Study

Background

The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice.

Methods and Findings

Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists’ views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively.

Conclusions

Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize ‘generalisability’ and incorporate it at the design stage of RCTs so that results are readily transferable to ‘real world’ practice.     

Long-term dietary intervention trials: critical issues and challenges

ABSTRACT: BACKGROUND: There are many challenges involved in running randomised controlled dietary intervention trials that investigate health outcomes. The aim of this paper was to evaluate the recruitment process, retention of participants and challenges faced in our dairy intervention trial, and to provide strategies to combat the difficulties of running long-term dietary intervention trials. METHODS: A 12-month, randomised, two-way crossover study in overweight adults with habitually low dairy food consumption designed to assess the effects of a high dairy intake (HD; 4 serves of reduced fat dairy per day) compared to a low dairy intake (LD; 1 serve of reduced fat dairy per day) on measures of cardiometabolic and cognitive health was conducted. On completion of the HD phase, each participant was interviewed about their experience in the trial and responses were used to evaluate the key issues for study participants. RESULTS: Although the recruitment target was achieved, high rates of attrition (49.3%) and difficulties maintaining participant compliance (reported by 37.8% of participants) were major threats to the viability of the study. Factors that contributed to the high attrition included inability to comply with the dietary requirements of the study protocol (27.0%), health problems or medication changes (24.3%) and time commitment (10.8%). CONCLUSIONS: Attrition and adherence to study requirements present challenges to trials requiring longer-term dietary change. Including a run-in period to further assess the motivation, commitment and availability of participants, maintaining regular contact with participants during control phases, minimising time commitment, providing flexibility with dietary requirements, facilitating positive experiences, and stringent monitoring of diet are some key recommendations for future dietary intervention trials.     

Economic evaluation alongside pragmatic randomised trials: developing a standard operating procedure for clinical trials units

Background

There is wide recognition that pragmatic randomised trials are the best vehicle for economic evaluation. This is because trials provide the best chance of ensuring internal validity, not least through the rigorous prospective collection of patient-specific data. Furthermore the marginal cost of collecting economic data alongside clinical data is typically modest. UK Clinical Research Collaboration (UKCRC) does not require a standard operating procedure (SOP) for economic evaluation as a prerequisite for trial unit registration. We judge that such a SOP facilitates the integration of health economics into trials.

Methods

A collaboration between health economists and trialists at Bangor University led to the development of a SOP for economic evaluation alongside pragmatic trials, in addition to the twenty SOPs required by UKCRC for registration, which include randomisation, data management and statistical analysis.

Results

Our recent telephone survey suggests that no other UKCRC-registered trials unit currently has an economic SOP.

Conclusion

We argue that UKCRC should require, from all Trials Units undertaking economic evaluation and seeking registration or re-registration, a SOP for economic evaluation as one of their portfolio of supporting SOPs.     

Using incentives to recruit physicians into behavioral trials: lessons learned from four studies

Objective

To describe lessons learned from the use of different strategies for recruiting physicians responsible for trauma triage, we summarize recruitment data from four behavioral trials run in the United States between 2010 and 2016.

Results

We ran a series of behavioral trials with the primary objective of understanding the influence of heuristics on physician decision making in trauma triage. Three studies were observational; one tested an intervention. The trials used different methods of recruitment (in-person vs. email), timing of the honorarium (pre-paid vs. conditional on completion), type of honorarium [a $100 gift card (monetary reward) vs. an iPad mini 2 (material incentive)], and study tasks (a vignette-based questionnaire, virtual simulation, and intervention plus virtual simulation). We recruited 989 physicians, asking each to complete a questionnaire or virtual simulation online. Recruitment and response rates were 80% in the study where we approached physicians in person, used a pre-paid material incentive, and required that they complete both an intervention plus a virtual simulation. They were 56% when we recruited physicians via email, used a monetary incentive conditional on completion of the task, and required that they complete a vignette-based questionnaire. Trial registration clinicaltrials.gov; NCT02857348

     

Strategies for increasing recruitment to randomised controlled trials: systematic review

Background

Recruitment of participants into randomised controlled trials (RCTs) is critical for successful trial conduct. Although there have been two previous systematic reviews on related topics, the results (which identified specific interventions) were inconclusive and not generalizable. The aim of our study was to evaluate the relative effectiveness of recruitment strategies for participation in RCTs.

Methods and Findings

A systematic review, using the PRISMA guideline for reporting of systematic reviews, that compared methods of recruiting individual study participants into an actual or mock RCT were included. We searched MEDLINE, Embase, The Cochrane Library, and reference lists of relevant studies. From over 16,000 titles or abstracts reviewed, 396 papers were retrieved and 37 studies were included, in which 18,812 of at least 59,354 people approached agreed to participate in a clinical RCT. Recruitment strategies were broadly divided into four groups: novel trial designs (eight studies), recruiter differences (eight studies), incentives (two studies), and provision of trial information (19 studies). Strategies that increased people''s awareness of the health problem being studied (e.g., an interactive computer program [relative risk (RR) 1.48, 95% confidence interval (CI) 1.00–2.18], attendance at an education session [RR 1.14, 95% CI 1.01–1.28], addition of a health questionnaire [RR 1.37, 95% CI 1.14–1.66]), or a video about the health condition (RR 1.75, 95% CI 1.11–2.74), and also monetary incentives (RR1.39, 95% CI 1.13–1.64 to RR 1.53, 95% CI 1.28–1.84) improved recruitment. Increasing patients'' understanding of the trial process, recruiter differences, and various methods of randomisation and consent design did not show a difference in recruitment. Consent rates were also higher for nonblinded trial design, but differential loss to follow up between groups may jeopardise the study findings. The study''s main limitation was the necessity of modifying the search strategy with subsequent search updates because of changes in MEDLINE definitions. The abstracts of previous versions of this systematic review were published in 2002 and 2007.

Conclusion

Recruitment strategies that focus on increasing potential participants'' awareness of the health problem being studied, its potential impact on their health, and their engagement in the learning process appeared to increase recruitment to clinical studies. Further trials of recruitment strategies that target engaging participants to increase their awareness of the health problems being studied and the potential impact on their health may confirm this hypothesis. Please see later in the article for the Editors'' Summary     

Incorporating a gender perspective into the development of clinical guidelines: a training course for guideline developers

Background

The Research-Based Education and Quality Improvement (ReBEQI) European partnership aims to establish a framework and provide practical tools for the selection, implementation, and evaluation of quality improvement (QI) interventions. We describe the development and preliminary evaluation of the software tool NorthStar, a major product of the ReBEQI project.

Methods

We focused the content of NorthStar on the design and evaluation of QI interventions. A lead individual from the ReBEQI group drafted each section, and at least two other group members reviewed it. The content is based on published literature, as well as material developed by the ReBEQI group. We developed the software in both a Microsoft Windows HTML help system version and a web-based version. In a preliminary evaluation, we surveyed 33 potential users about the acceptability and perceived utility of NorthStar.

Results

NorthStar consists of 18 sections covering the design and evaluation of QI interventions. The major focus of the intervention design sections is on how to identify determinants of practice (factors affecting practice patterns), while the major focus of the intervention evaluation sections is on how to design a cluster randomised trial. The two versions of the software can be transferred by email or CD, and are available for download from the internet. The software offers easy navigation and various functions to access the content. Potential users (55% response rate) reported above-moderate levels of confidence in carrying out QI research related tasks if using NorthStar, particularly when developing a protocol for a cluster randomised trial

Conclusion

NorthStar is an integrated, accessible, practical, and acceptable tool to assist developers and evaluators of QI interventions.     

The Effects of Intravenous Immunoglobulins in Women with Recurrent Miscarriages: A Systematic Review of Randomised Trials with Meta-Analyses and Trial Sequential Analyses Including Individual Patient Data

Background

Immunological disturbances are hypothesised to play a role in recurrent miscarriage (RM) and therefore intravenous immunoglubulins (IVIg) have been tested in RM patients.

Objectives

The objectives were to investigate the benefits and harms of IVIg versus placebo, no intervention, or treatment as usual in women with RM.

Search Strategy

We searched the published literature in all relevant databases.

Selection Criteria

Randomised trials investigating IVIg versus placebo, no intervention, or treatment as usual in women with RM.

Data Collection and Analysis

We undertook meta-analyses of aggregated data and individual patient data using a two-step approach, and we conducted bias domain assessments and trial sequential analyses to assess the risks of systematic and random errors.

Main Results

We identified 11 randomised clinical trials. No significant difference in the frequency of no live birth was found when IVIg was compared with placebo or treatment as usual (RR 0.92, 95% CI 0.75–1.12, p = 0.42). Trial sequential analysis showed that the required information size of 1,008 participants was not obtained. IVIg compared with placebo seems to increase the risk of adverse events. Subgroup analysis suggests that women with RM after a birth (secondary RM) seemed most likely to obtain a potential beneficial effect of IVIg (RR for no live birth 0.77, 95%CI 0.58–1.02, p = 0.06), however, trial sequential analysis showed that insufficient information is presently accrued.

Conclusion

We cannot recommend or refute IVIg in women with RM. IVIg should therefore be assessed in further randomised clinical trials with positive outcomes before any clinical use is considered.     

Male inclusion in randomized controlled trials of lifestyle weight loss interventions

The prevalence of obesity is similar for men (32.2%) and women (35.5%). It has been assumed that lifestyle weight loss interventions have been developed and tested in predominately female samples, but this has not been systematically investigated. The aim of this review was to investigate total and ethnic male inclusion in randomized controlled trials of lifestyle interventions. PUBMED, MEDLINE, and PSYCHINFO were searched for randomized controlled trials of lifestyle weight loss interventions (N = 244 studies with a total of 95,207 participants) published in the last 10 years (1999-2009). A trial must be in English, included weight loss as an outcome, and tested a dietary, exercise, and/or other behavioral intervention for weight loss. Results revealed samples were on average 27% male vs. 73% female (P < 0.001). Trials recruiting a diseased sample included a larger proportion of males than those not targeting a disease (35% vs. 21%; P < 0.001). About 32% of trials used exclusively female samples, whereas only 5% used exclusively male samples (P < 0.001). No studies in the past 10 years specifically targeted minority males. Ethnic males identified composed 1.8% of total participants in US studies. Only 24% of studies that underrepresented males provided a reason. Males, especially ethnic males, are underrepresented in lifestyle weight loss trials.     

Applying results of randomised trials to clinical practice: impact of losses before randomisation.

The problem of generalisability in randomised clinical trials was highlighted by studies that entered only 10-14% of screened patients. To determine the magnitude and source of prerandomisation losses in clinical trials a survey was conducted of 41 trials listed in the 1979 inventory of the National Institute of Health. Two thirds of the trials maintained screening logs, but only half maintained any records of the number of patients who met the eligibility criteria but were not entered into the trial. Among 21 trials (51%) that kept data on the number of patients who were eligible but not entered, losses of eligible subjects were attributable to refusals by patients in 25% and refusals by physicians in 29%. Other protocol requirements accounted for the remaining losses of eligible patients. Only a few trials documented the characteristics of patients who were eligible but not entered; in those trials the patients who were not entered were similar demographically but differed clinically from those enrolled. Thus minimising prerandomisation losses of eligible patients requires the use of less restrictive criteria for entering patients. Twenty four of the trials achieved 75% or more of their recruitment goals, eight between 25% and 74%, and six less than 25%. Among trials that screened less than twice their projected sample size, only three out of 13 (23%) achieved 75% or more of their recruitment goal. By contrast, 12 out of 16 trials (75%) that screened more than twice their projected sample size achieved 75% or more of their recruitment goal. Screening large numbers of patients appears to be a pragmatic requirement for success in achieving recruitment goals; therefore, trials should not be criticised as lacking generalisability on that basis alone. The number and characteristics of eligible patients who were not entered, however, were documented by only a few trials; these data are critical in the assessment of generalisability. Additionally, the number of patients with the index disease who did not meet the eligibility criteria should also be documented. Together, these two types of data characterise the population to whom the trial results may be applied.     

Multifactorial day hospital intervention to reduce falls in high risk older people in primary care: a multi-centre randomised controlled trial [ISRCTN46584556]

Background

There are many barriers to patient participation in randomised controlled trials of cancer treatments. To increase participation in trials, strategies need to be identified to overcome these barriers. Our aim was to assess the effectiveness of interventions to overcome barriers to patient participation in randomised controlled trials (RCTs) of cancer treatments.

Methods

A systematic review was conducted. Published and unpublished studies in any language were searched for in fifteen electronic databases, including MEDLINE, EMBASE, CINAHL and PsycINFO, from inception to the end of 2004. Studies of any interventions to improve cancer patient participation in RCTs, which reported the change in recruitment rates, were eligible for inclusion. RCTs and non-randomised controlled trials as well as before and after studies reporting baseline rates specific to the population being investigated were included. Data were extracted by one reviewer into structured summary tables and checked for accuracy by a second reviewer. Each included study was assessed against a checklist for methodological quality by one reviewer and checked by a second reviewer. A narrative synthesis was conducted.

Results

Eight studies were identified that met the inclusion criteria: three RCTs, two non-randomised controlled trials and three observational studies. Six of the studies had an intervention that had some relevance to the UK. There was no robust evidence that any of the interventions investigated led to an increase in cancer patient participation in RCTs, though one good quality RCT found that urologists and nurses were equally effective at recruiting participants to a treatment trial for prostate cancer. Although there was no evidence of an effect in any of the studies, the evidence was not of sufficient quality to be able to conclude that these interventions therefore do not work.

Conclusion

There is not a strong evidence-base for interventions that increase cancer patient participation in randomised trials. Further research is required to evaluate the effectiveness of strategies to increase participation in cancer treatment trials.     

Informing participants of allocation to placebo at trial closure: postal survey

ObjectivesTo assess whether and how investigators of placebo controlled randomised trials inform participants of their treatment allocation at trial closure and to assess barriers to feedback.DesignPostal survey with a semistructured questionnaire.ParticipantsAll investigators who published a placebo controlled randomised trial in 2000 in five leading medical journals, and a random sample of 120 trials listed in the national research register database.Results45% of investigators informed either all or most participants of their treatment allocation, and 55% did not inform any participant or only informed those who asked. The main reasons for not informing participants were that the investigators never considered this option (40%) or to avoid biasing results at study follow up (24%).ConclusionFurther research is required to examine sensitive ways to communicate treatment information to trial participants.

What is already known on this topic

Information is poor on the nature, extent, and effect of informing participants of placebo controlled randomised trials about their treatment allocation at trial closureLess than 50% of participants receiving placebo are informed about their treatment allocation

What this study adds

No standard procedure is available for informing patients of their treatment arm or of study results at the end of a trialEffective and sensitive ways of communicating treatment allocation to participants are required, as is information on the effects on placebo responders     

Randomised controlled feasibility trial of an evidence-informed behavioural intervention for obese adults with additional risk factors

Background

Interventions for dietary and physical activity changes in obese adults may be less effective for participants with additional obesity-related risk factors and co-morbidities than for otherwise healthy individuals. This study aimed to test the feasibility and acceptability of the recruitment, allocation, measurement, retention and intervention procedures of a randomised controlled trial of an intervention to improve physical activity and dietary practices amongst obese adults with additional obesity related risk factors.

Method

Pilot single centre open-labelled outcome assessor-blinded randomised controlled trial of obese (Body Mass Index (BMI)≥30 kg/m2) adults (age≥18 y) with obesity related co-morbidities such as type 2 diabetes, impaired glucose tolerance or hypertension. Participants were randomly allocated to a manual-based group intervention or a leaflet control condition in accordance to a 2∶1 allocation ratio. Primary outcome was acceptability and feasibility of trial procedures, secondary outcomes included measures of body composition, physical activity, food intake and psychological process measures.

Results

Out of 806 potentially eligible individuals identified through list searches in two primary care general medical practices N = 81 participants (63% female; mean-age = 56.56(11.44); mean-BMI = 36.73(6.06)) with 2.35(1.47) co-morbidities were randomised. Scottish Index of Multiple Deprivation (SIMD) was the only significant predictor of providing consent to take part in the study (higher chances of consent for invitees with lower levels of deprivation). Participant flowcharts, qualitative and quantitative feedback suggested good acceptance and feasibility of intervention procedures but 34.6% of randomised participants were lost to follow-up due to overly high measurement burden and sub-optimal retention procedures. Participants in the intervention group showed positive trends for most psychological, behavioural and body composition outcomes.

Conclusions

The intervention procedures were found to be acceptable and feasible. Attrition rates were unacceptably high and areas for improvements of trial procedures were identified.

Trial Registration

Controlled-Trials.com ISRCTN90101501     

Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials

Background

Recruitment of sufficient participants in an efficient manner is still widely acknowledged to be a major challenge to the mounting and completion of randomised controlled trials (RCTs). Few recruitment interventions have involved staff undertaking recruitment. This study aimed i) to understand the recruitment process from the perspective of recruiters actively recruiting RCT participants in six pragmatic RCTs, and ii) to identify opportunities for interventions to improve recruitment.

Methods

Interviews were undertaken with 72 individuals (32 doctors or RCT Chief investigators (CIs); 40 nurses/other health professionals) who were actively recruiting participants in six RCTs to explore their experiences of recruitment. The RCTs varied in scale, duration, and clinical contexts. Interviews were fully transcribed and analysed using qualitative content and thematic analytic methods derived from grounded theory. For this analysis, data were systematically extracted from each RCT and synthesised across all six RCTs to produce a detailed and nuanced understanding of the recruitment process from the perspectives of the recruiters.

Results

Recruiters readily identified organisational difficulties, fewer than expected eligible patients, and patients’ treatment preferences as the key barriers to recruitment. As they described their experiences of recruitment, several previously hidden issues related to their roles as researchers and clinicians emerged, imbued with discomfort and emotion. The synthesis across the RCTs showed that doctors were uncomfortable about aspects of patient eligibility and the effectiveness of interventions, whereas nurses were anxious about approaching potential RCT participants and conflicts between the research and their clinical responsibilities. Recruiters seemed unaware that their views contributed to recruitment difficulties. Their views were not known to RCT CIs. Training and support needs were identified for both groups of staff.

Conclusions

The synthesis showed that recruitment to these RCTs was a complex and fragile process. Clear obstacles were identified but hidden challenges related to recruiters’ roles undermined recruitment, unbeknown to RCT CIs. Qualitative research can elicit and identify the hidden challenges. Training and support are then needed for recruiters to become more comfortable with the design and principles of RCTs, so that they can engage more openly with potentially eligible participants and create a more resilient recruitment process.