Do patients with type 2 diabetes mellitus included in randomised clinical trials differ from general-practice patients? A cross-sectional comparative study.

OBJECTIVES: To compare the characteristics of patients with type 2 diabetes mellitus in general practice and those included in randomised controlled trials on which clinical practice guidelines are based. DESIGN: Cross-sectional comparative study. SETTING: We asked 45 general practitioners from three French Departments to identify the 15 patients with type 2 diabetes mellitus they most recently saw in consultation. In parallel, we selected randomised controlled trials included in the Cochrane systematic review on which the clinical practice guidelines for type 2 diabetes mellitus were based. PARTICIPANTS: We included 675 patients with type 2 diabetes mellitus, and data were collected from 23 randomised controlled trials, corresponding to 36 059 patients. OUTCOME MEASURES: Characteristics of general-practice patients were extracted from medical records by a unique observer. The same baseline characteristics of patients included in randomised controlled trials from the Cochrane systematic review were extracted and meta-analysed. We assessed standardised differences between these two series of baseline characteristics. A difference greater than 0.10 in absolute value was considered meaningful. RESULTS: General-practice patients were older than randomised controlled trial patients (mean (SD) 68.8 (1.1) vs 59.9 years (standardised difference 0.8)) and had a higher body mass index (mean (SD) 31.5 (6.9) vs 28.2 kg/m2 (standardised difference 0.5)) but smoked less (11.0% vs 29.3% (standardised difference -0.6)). They more frequently used antihypertensive drugs (82.1% vs 37.5% (standardised difference 1.2)) but less frequently had a myocardial infarction (7.6% vs 23.1% (standardised difference -1.1)). CONCLUSIONS: Patients with type 2 diabetes mellitus cared for in general practice differ in a number of important aspects from patients included in randomised controlled trials on which clinical practice guidelines are based. This situation hampers the applicability of these guidelines. Future randomised trials should include patients who better fit the 'average' general-practice patient with type 2 diabetes mellitus to help improve the translation of study findings in daily practice.

A tailored psychological intervention for anxiety and depression management in people with chronic obstructive pulmonary disease: TANDEM RCT and process evaluation.

Background: People with chronic obstructive pulmonary disease have high levels of anxiety and depression, which is associated with increased morbidity and poor uptake of effective treatments, such as pulmonary rehabilitation. Cognitive-behavioural therapy improves mental health of people with long-term conditions and could potentially increase uptake of pulmonary rehabilitation, enabling synergies that could enhance the mental health of people with chronic obstructive pulmonary disease. Aim: Our aim was to develop and evaluate the clinical effectiveness and cost effectiveness of a tailored cognitive-behavioural approach intervention, which links into, and optimises the benefits of, routine pulmonary rehabilitation. Design: We carried out a pragmatic multicentre randomised controlled trial using a 1.25 : 1 ratio (intervention : control) with a parallel process evaluation, including assessment of fidelity. Setting: Twelve NHS trusts and five Clinical Commissioning Groups in England were recruited into the study. The intervention was delivered in participant's own home or at a local NHS facility, and by telephone. Participants: Between July 2017 and March 2020 we recruited adults with moderate/very severe chronic obstructive pulmonary disease and mild/moderate anxiety and/or depression, meeting eligibility criteria for assessment for pulmonary rehabilitation. Carers of participants were invited to participate. Intervention: The cognitive-behavioural approach intervention (i.e. six to eight 40- to 60-minute sessions plus telephone support throughout pulmonary rehabilitation) was delivered by 31 trained respiratory healthcare professionals to participants prior to commencing pulmonary rehabilitation. Usual care included routine pulmonary rehabilitation referral. Main outcome measures: Co-primary outcomes were Hospital Anxiety and Depression Scale - anxiety and Hospital Anxiety and Depression Scale - depression at 6 months post randomisation. Secondary outcomes at 6 and 12 months included health-related quality of life, smoking status, uptake of pulmonary rehabilitation and healthcare use. Results: We analysed results from 423 randomised participants (intervention, n = 242; control, n = 181). Forty-three carers participated. Follow-up at 6 and 12 months was 93% and 82%, respectively. Despite good fidelity for intervention delivery, mean between-group differences in Hospital Anxiety and Depression Scale at 6 months ruled out clinically important effects (Hospital Anxiety and Depression Scale - anxiety mean difference -0.60, 95% confidence interval -1.40 to 0.21; Hospital Anxiety and Depression Scale - depression mean difference -0.66, 95% confidence interval -1.39 to 0.07), with similar results at 12 months. There were no between-group differences in any of the secondary outcomes. Sensitivity analyses did not alter these conclusions. More adverse events were reported for intervention participants than for control participants, but none related to the trial. The intervention did not generate quality-of-life improvements to justify the additional cost (adjusted mean difference £770.24, 95% confidence interval -£27.91 to £1568.39) to the NHS. The intervention was well received and many participants described positive affects on their quality of life. Facilitators highlighted the complexity of participants' lives and considered the intervention to be of potential valuable; however, the intervention would be difficult to integrate within routine clinical services. Our well-powered trial delivered a theoretically designed intervention with good fidelity. The respiratory-experienced facilitators were trained to deliver a low-intensity cognitive-behavioural approach intervention, but high-intensity cognitive-behavioural therapy might have been more effective. Our broad inclusion criteria specified objectively assessed anxiety and/or depression, but participants were likely to favour talking therapies. Randomisation was concealed and blinding of outcome assessment was breached in only 15 participants. Conclusions: The tailored cognitive-behavioural approach intervention delivered with fidelity by trained respiratory healthcare professionals to people with chronic obstructive pulmonary disease was neither clinically effective nor cost-effective. Alternative approaches that are integrated with routine long-term condition care are needed to address the unmet, complex clinical and psychosocial needs of this group of patients. Trial registration: This trial is registered as ISRCTN59537391. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/146/02) and is published in full in Health Technology Assessment; Vol. 28, No. 1. See the NIHR Funding and Awards website for further award information.

People with long-standing lung problems, such as chronic obstructive pulmonary disease, often also have anxiety and depression, which further reduces their quality of life. Two existing treatments could help. Pulmonary rehabilitation (a programme of exercise and education) improves both the physical and mental health of people with chronic obstructive pulmonary disease. Cognitive­behavioural therapy (a talking therapy) may reduce anxiety and depression. The TANDEM [Tailored intervention for Anxiety and Depression Management in chronic obstructive pulmonary disease (COPD)] intervention linked these two treatments by providing talking therapy based on cognitive­behavioural therapy during the waiting time following referral for pulmonary rehabilitation. The TANDEM treatment was delivered by respiratory healthcare professionals (e.g. nurses or physiotherapists) trained to deliver the talking therapy in six to eight weekly sessions. The sessions were conducted in the participant's home (or another convenient location), with brief telephone support during the pulmonary rehabilitation. Of 423 participants recruited to the study, 242 participants received TANDEM talking therapy and 181 participants received usual care (including a referral to pulmonary rehabilitation). We measured mental health, quality of life, social life, attendance at pulmonary rehabilitation and healthcare use in both groups at 6 and 12 months. Forty-three carers joined the study and we assessed their mental well-being. We interviewed patients, carers and health professionals to find out their views and experience of the TANDEM treatment. We also examined whether or not the TANDEM treatment was good value for money. The TANDEM treatment did not improve the mental or the physical health of people with chronic obstructive pulmonary disease. In addition, the TANDEM treatment cost the NHS an extra £770 per patient, which was not good value for money. The TANDEM treatment was well received, and many participants told us how it had helped them. Heath-care professionals noted how participants did not just have chronic obstructive pulmonary disease, but were coping with many physical, mental and social problems. The TANDEM intervention was not effective and, therefore, other strategies will be needed to help people with chronic obstructive pulmonary disease and mental health problems live with their condition.

Impact d'une consultation de médecine des voyages sur les attitudes et les pratiques des voyageurs.

Introduction : Traveling regularly to malaria endemic areas increasingly exposes travelers to various risks which could be mitigated by a pre-travel health consultation. The objective was to study the impact of advice provided during a pre-travel consultation on travelers’ behaviors and practices to identify travelers’ profiles and adapt the prevention recommendations before trave-ling to intertropical zones.Methods : Two self-assessment questionnaires (Q1-before and Q2-after travelling) were proposed to 271 individuals over 5 months of traveler consultations to assess behaviors (Q1) and practices (Q2). Questionnaires gathered travelers’ profiles, source of information, travel diet and lifestyle, personal vector control, malaria chemoprophylaxis and other frequent risks.Results : Diet recommendations were the least followed (16 %), especially for people<55 (p<0.03) as well as Visiting Friends and Relatives (VFR) (p<0,001). A correlation between behaviors and practices for personal vector control and immunization and malaria chemoprophylaxis were found (resp. 89% and 78%). Mosquito nets and long sleeve clothes were underused. Changes of opinion resulting from concerns of potential side effects and lack of efficiency (<7%) explained the non-compliance to the pre-travel recommendations. During the stay, although 24% of travelers got sick, medical consultations (<5%) and hospital admissions (<1%) remained low. The General Practitioner remains the main point of contact (41%).Discussion : Better identifying travelers’ characteristics would allow to improve travel consultation, to refer to their knowledge and focus on preventive measures. It is crucial to highlight the importance of diet measures and insist on the low likelihood of adverse effects in Malaria Chemoprophylaxis.

Intervention effect estimates in randomised controlled trials conducted in primary care versus secondary or tertiary care settings: a meta-epidemiological study.

BACKGROUND: Many clinical practice guidelines are based on randomised controlled trials conducted in secondary or tertiary care setting and general practitioners frequently question their relevance for primary care patients. Our aim was to compare the intervention effect estimates between primary care setting randomised controlled trials (PC-RCTs) and secondary or tertiary care setting randomised controlled trials (ST-RCTs). METHODS: Meta-epidemiological study of meta-analyses (MAs) of a binary outcome including at least one PC-RCT and one ST-RCT. PC-RCTs were defined as trials recruiting patients in general practices, primary care practices, family practices, community centers or community pharmacies. ST-RCTs were defined as trials recruiting in hospitals, including hospitalized patients, hospital outpatients and patients from emergency departments. For each MA, we estimated a ratio of odds ratio (ROR) by using random-effects meta-regression, with an ROR less than 1 indicating lower estimates of the intervention effect in PC-RCTs than ST-RCTs. Finally, we estimated a combined ROR across MAs by using a random-effects meta-analysis. We performed subgroup analyses considering the type of outcomes (objective vs subjective), type of experimental intervention (pharmacological vs non-pharmacological), and control group (active vs inactive) as well as analyses adjusted on items of the Cochrane Risk of Bias tool. RESULTS: Among 1765 screened reviews, 76 MAs with 230 PC-RCTs and 384 ST-RCTs were selected. The main medical fields were pneumology (13.2%) and psychiatry or addictology (38.2%). Intervention effect estimates did not significantly differ between PC-RCTs and ST-RCTs (ROR = 0.97, 95% confidence interval 0.88 to 1.08), with moderate heterogeneity across MAs (I2 = 45%). Subgroup and adjusted analyses led to consistent results. CONCLUSION: We did not observe any significant difference in intervention effect estimates between PC-RCTs and ST-RCTs. Nevertheless, most of the medical fields in this meta-epidemiological study were not representative of the pathologies encountered in primary care. Further studies with pathologies more frequently encountered in primary care are needed.

Intermediate care in caring for dementia, the point of view of general practitioners: A key informant survey across Europe.

Background: Intermediate care is often defined as healthcare occurring somewhere between traditional primary (community) and secondary (hospital) care settings. High quality intermediate care is important in dementia, may prevent caregiver burnout and also lead to optimal care for people with dementia. However, very little is known about the point of intermediate care for persons with dementia in Europe. Research questions: What intermediate care services exist and how are they utilized in the care of people with dementia in Europe? Objective: This study aims at describing the point of view of General Practitioners on intermediate care services for people with dementia across Europe. Methods: Key informant survey was sent to GPs via a self-developed questionnaire with space for open ended comments. 16 European countries participated to this cross-sectional mixed method study. Given the volunteer nature of the study, no minimum sample size requirements were applied to participation. Convenience sampling technique was used to address variations due to regional variations and regulations within the same country. Descriptive analyses of all intermediate care facilities groups by countries were performed. Qualitative analyses approach was used for the optional-free text to exemplify and/or complete the reasons contained in the closed response categories. Results: The questionnaire was sent to 16 European countries. 583 questionnaires were analyzed. The responding physicians were 48 (± 11) years old on average and they had been in practice for an average of 18 (+ /11) years. The types of intermediate care considered were integrated at-home services, respite and relief services, day care centers and nursing homes. Their availability was considered very inhomogeneous by the majority of respondents. The main benefits of intermediate care cited were better medical care for the patient (78%), better quality of life for the caregiver (67%), prevention of the caregiver burden (73%) and a break for the caregiver (59%). The reported difficulties were: accessing these facilities due to limited financial support (76%) and cumbersome administrative procedures (67%). Many other facets of our findings were captured in the qualitative themes that emerged. Conclusion: Intermediate care in Europe is diverse and heterogeneous. Major concerns of GPs are about the cost issues and the cumbersome administrative procedures to access them.

Management of death-related noncompleters in cluster randomized trials carried out in nursing homes: a methodological review.

BACKGROUND: A noncompleter is defined as a participant who leaves a trial before the end of the planned follow-up. Research in nursing homes is highly exposed to this problem because of high death rates. OBJECTIVES: The aim of this trial is to assess the statistical management of noncompleters in cluster randomized trials carried out in nursing homes. STUDY DESIGN AND SETTING: A methodological review of published cluster randomized trials. RESULTS: We selected 37 articles. For 22 (59%) trials, the design was closed-cohort (i.e., participants included all at the same time when randomizing clusters). In those 22 closed-cohort trials, the median follow-up was 6.5 months (interquartile range 4-12). The median noncompleter rate was 19.5% and the median noncompletions due to death was 73.2%. In only one trial were the baseline characteristics of completers and noncompleters compared. Strategies to deal with noncompleters were an inflation of the planned sample size (11 trials), the use of repeated measurements of the outcome (12 trials), and the use of imputation methods when analyzing data (7 trials). CONCLUSION: In cluster randomized trials of nursing homes, noncompleters are managed as for any missing data, but they are essentially due to death. Methodological and statistical developments and guidance are needed.

Impact of a phone call with a medical student/general practitioner team on morbidity of chronic patients during the first French COVID-19 lockdown (COVIQuest): a cluster randomised trial.

OBJECTIVES: The first COVID-19 lockdown led to a significantly reduced access to healthcare, which may have increased decompensations in frail patients with chronic diseases, especially older patients living with a chronic cardiovascular disease (CVD) or a mental health disorder (MHD). The objective of COVIQuest was to evaluate whether a general practitioner (GP)-initiated phone call to patients with CVD and MHD during the COVID-19 lockdown could reduce the number of hospitalisation(s) over a 1-month period. DESIGN: This is a cluster randomised controlled trial. Clusters were GPs from eight French regions. PARTICIPANTS: Patients ≥70 years old with chronic CVD (COVIQuest_CV subtrial) or ≥18 years old with MHD (COVIQuest_MH subtrial). INTERVENTIONS: A standardised GP-initiated phone call aiming to evaluate patients' need for urgent healthcare, with a control group benefiting from usual care (ie, the contact with the GP was by the patient's initiative). MAIN OUTCOME MEASURES: Hospital admission within 1 month after the phone call. RESULTS: In the COVIQuest_CV subtrial, 131 GPs and 1834 patients were included in the intervention group and 136 GPs and 1510 patients were allocated to the control group. Overall, 65 (3.54%) patients were hospitalised in the intervention group vs 69 (4.57%) in the control group (OR 0.82, 95% CI 0.56 to 1.20; risk difference -0.77, 95% CI -2.28 to 0.74). In the COVIQuest_MH subtrial, 136 GPs and 832 patients were included in the intervention group and 131 GPs and 548 patients were allocated to the control group. Overall, 27 (3.25%) patients were hospitalised in the intervention group vs 12 (2.19%) in the control group (OR 1.52, 95% CI 0.82 to 2.81; risk difference 1.38, 95% CI 0.06 to 2.70). CONCLUSION: A GP-initiated phone call may have been associated with more hospitalisations within 1 month for patients with MHD, but results lack robustness and significance depending on the statistical approach used. TRIAL REGISTRATION NUMBER: NCT04359875.

The TANDEM trial: protocol for the process evaluation of a randomised trial of a complex intervention for anxiety and/or depression in people living with chronic obstructive pulmonary disease (COPD).

BACKGROUND: TANDEM is a randomised controlled trial of a complex healthcare intervention to improve the psychological and physical health of people living with chronic obstructive pulmonary disease (COPD) and anxiety and/or depression. Based on health psychology theory set out in a logic model, respiratory health professionals were recruited and trained to deliver a cognitive behavioural approach intervention (The TANDEM intervention) under the supervision of senior cognitive behavioural practitioners. Here, we describe the protocol for the process evaluation commissioned alongside the trial. A realist approach that includes attention to describing contexts and mechanisms has been adopted. METHODS: We set up a multi-disciplinary team to develop and deliver the process evaluation. The mixed-methods design incorporates quantitative process data; monitoring of intervention fidelity; qualitative interviews with patients, carers, health professionals (facilitators) and clinical supervisors about their perspectives on acceptability of the intervention; and exploration with all stakeholders (including management/policy-makers) on future implementation. Normalisation process theory (NPT) will inform data collection and interpretation with a focus on implementation. Quantitative process data will be analysed descriptively. Qualitative interview data will be analysed before the trial outcomes are known using analytic induction and constant comparison to develop themes. Findings from the different elements will be reported separately and then integrated. CONCLUSION: Detailed description and analysis of study processes in a research trial such as TANDEM enables research teams to describe study contexts and mechanisms and to examine the relationship with outcomes. In this way, learning from the trial goes beyond the randomised control trial (RCT) model where effectiveness is prioritised and makes it possible to explore issues arising for post-trial study implementation. TRIAL REGISTRATION: ISRCTN ISRCTN59537391 . Registered on 20 March 2017. Trial protocol version 6.0, 22 April 2018. Process evaluation protocol version 4.0, 1 November 2020.

How pragmatic are the randomised trials used in recommendations for control of glycosylated haemoglobin levels in type 2 diabetic patients in general practice: an application of the PRECIS II tool.

BACKGROUND: Recommendations for good clinical practice have been reported to be difficult to apply in real life by primary care clinicians. This could be because the clinical trials at the origin of the guidelines are based on explanatory trials, conducted under ideal conditions not reflecting the reality of primary care, rather than pragmatic trials conducted under real-life conditions. The objective of this study was to evaluate how pragmatic are the clinical trials used to build the French High Authority of Health's recommendations on the management of type II diabetes. METHODS: Trials from the 2013 Cochrane meta-analysis that led to the 2013 French High Authority of Health's recommendations on the management of type II diabetes were selected. Each trial was analysed by applying the PRECIS-2 tool to evaluate whether the trial was pragmatic or explanatory, according to the nine domains of PRECIS-2. Each domain was scored between 1 (very explanatory) and 5 (very pragmatic) by two blinded researchers, and consensus was reached with a third researcher in case of discrepancy. Median scores were calculated for each of the nine domains. RESULTS: Twenty-three articles were analysed. Eight out of nine domains - namely eligibility, recruitment, setting, organisation, flexibility of delivery, flexibility of adherence, follow-up, and primary outcome - had a median score of less than 3, indicating a more explanatory design. Only the primary analysis domain had a score indicating a more pragmatic approach (median score of 4). In more than 25% of the articles, data to score the domains of recruitment, flexibility of delivery, flexibility of adherence, and primary analysis were missing. CONCLUSIONS: Trials used to build French recommendations for good clinical practice for the management of type 2 diabetes in primary care were more explanatory than pragmatic. Policy-makers should encourage the funding of pragmatic trials to evaluate the different strategies proposed for managing the patient's treatment according to HbA1C levels and give clinicians feasible recommendations.

Patients' adherence to optimal therapeutic, lifestyle and risk factors recommendations after myocardial infarction: Six years follow-up in primary care.

BACKGROUND: The 20% observed mortality within 5 years among survivors of myocardial infarction may be explained in part by non-adherence to the recommended treatment over the long term. MAIN OBJECTIVE: To investigate post-myocardial infarction patients' adherence to the therapeutic, lifestyle and risk factor control recommendations of the French health authority over 6 years. MATERIALS AND METHODS: A cohort of survivors of myocardial infarction established in Tours in 2009 was followed over 6 years. The general practitioner of the patients included in the first 1-year follow-up study was contacted to collect data on treatments, cardiovascular risk factors and lifestyle between January and June 2015. Data were described and compared with the recommendations and predictors of achieving all the recommended targets were determined. RESULTS: A total of 97 patients (52%) among the 185 patients who underwent a coronary angioplasty for MI were included at baseline. Treatment was adapted by the general practitioner on the advice on the cardiologist for 75% (73/97) patients, by both of them for 12% (12/97) and by the general practitioner alone for 7% (7/97) patients. Among the 97 initial patients, 62 were included in the final analysis at 6 years. Fatal events rate was 5% (5/97) at 1 year and 12% (11/91) at 6 years. Non-fatal events rate was 44% (43/97) at 6 months, 19% (17/91) at 1 year and 29% (18/62) at 6 years. Six years after the myocardial infarction, 6 (10%) patients achieved the recommended targets in terms of prescriptions of treatment, risk factors and lifestyle targets. Exposure to a cardiac rehabilitation program after a myocardial infarction was associated with long-term achievement of optimal therapeutic objectives (OR = 7.31 [95% CI 1.74; 44.88], p<0.002). CONCLUSION: Our data show suboptimal long-term adherence to secondary prevention treatment in this high-risk population of survivors of myocardial infarction, which seems to be improved in patients exposed to a cardiac rehabilitation program.

Heterogeneous perception of the ethical legitimacy of unbalanced randomization by institutional review board members: a clinical vignette-based survey.

BACKGROUND: Institutional review boards must guarantee the ethical acceptability of a randomized controlled trial before it is conducted. However, some may regard an unbalanced randomization ratio as reflecting an absence of uncertainty between the groups being compared. The objective was to assess institutional review board members' perceptions of whether unbalanced randomization in randomized controlled trials is justified and ethically acceptable. METHODS: Institutional review board members worldwide completed a survey involving clinical vignettes modeling situations classically advocated to explain the use of unbalanced randomization. Institutional review board members were asked whether unbalanced randomization was justified and ethically sound. Answers were collected by using visual analog scales. Data were analyzed by principal component analysis, and a hierarchical ascending classification was created. Verbatim answers were assessed by qualitative content analysis. RESULTS: We analyzed responses from 148 institutional review board members. Three classes of respondents were identified: class 1 (n = 58; 39.2%), mostly skeptics who disagreed with unbalanced randomization, whatever the justification; class 2 (n = 46; 31.1%), believers who considered that unbalanced randomization was acceptable whatever the justification, except cost; and class 3 (n = 44; 29.7%), circumstantial believers for whom unbalanced randomization may be justified for methodological and safety issues but not cost or ethical issues. When institutional review board members were asked whether unbalanced randomization respected the equipoise principle, the mean quotation was low (4.5 ± 3.3 out of 10), especially for class 1 members. CONCLUSIONS: Institutional review board members perceive unbalanced randomization heterogeneously in terms of its justification and its ethical validity.

Cross-sectional multicentre study on the cohort of all the French junior lecturers in general practice.

BACKGROUND: General practice became an academic discipline quite recently in many western countries. In France, junior lecturer work is specified in a three-part mandate: medical work in general practice, teaching in the university, and research. Since 2007, 130 junior lecturers have been appointed in general practice. The aim of the creation of junior lecturer status was to align general practice with other specialties and to develop research and education in primary care. OBJECTIVES: To describe the healthcare, teaching and research undertaken by junior lecturers in general practice, practising in October 2014. METHODS: A cross-sectional multicentre study using an online self-administered questionnaire on the cohort composed of all the junior lecturers in general practice with open questions and the qualitative analysis of written verbatim accounts. RESULTS: Of the 95 junior lecturers practising at the date of the study, 75 (79%) responded; average age 32 years; gender ratio (F/M) 2.4:1. They spent five, two and three half-days per week respectively in healthcare, teaching and research. The healthcare activity was predominantly carried out in the community (73%). Thirty-nine per cent worked as part of a multi-professional team taking on 50 consultations per week. Most of the educational work involved lecturing and mentoring students specializing in general practice (median 86 hours per year). Research output increased during the fellowship. Research topics were varied and relevant to the disciplinary field. CONCLUSION: During the fellowship, the balancing, and even the reinforcement, of healthcare and research contributions were accompanied by a significant investment in educational provision.

ESCAPE ancillary blood pressure measurement study 2: changes in end-digit preference after 2 years of a cluster randomized trial.

OBJECTIVE: The aim of the ESCAPE AMPA 2 trial was to describe the evolution of end-digit preference (EDP) practices in primary care after 2 years of trial. METHODS: A descriptive analysis of the EDP in the intervention group (IG) and in the electronic control group (ECG) of the ESCAPE trial and a comparative analysis of EDP changes in blood pressure (BP) measures of both groups were carried out between baseline and 2 years. In the ESCAPE trial, physicians in the IG were new users of electronic devices provided in the trial to measure their patients' BP and physicians in the ECG were former users of electronic devices. Hierarchical mixed-effects models were used for statistical analysis in a pragmatic cluster randomized-controlled trial. RESULTS: After 2 years, the proportion of BP measures ending with a 0 or a 5 was significantly higher in the ECG than in the IG (50.4 vs. 33.4%, P<0.0001). There was no significant change in EDP tendency between baseline and the end of the trial in the ECG (65.6-56.7%, P=0.39) and in the IG (29.6-38.2%, P=0.07), with a between-groups P value of 0.11. Over 2 years, there was no significant change in systematic EDP in the ECG (18.8-20.0%, P=0.29) and in the IG (4.8-10.6%, P=0.01), with a between-groups P value of 0.17. CONCLUSION: EDP is not eliminated by electronic devices and tends to increase with time for new users.

Unbalanced rather than balanced randomized controlled trials are more often positive in favor of the new treatment: an exposed and nonexposed study.

OBJECTIVES: We aimed to assess whether the clinical equipoise principle is satisfied in unbalanced randomized controlled trials (RCTs) (i.e., with an unequal probability of subjects being allocated to one group than another). STUDY DESIGN AND SETTING: Observational and comparative study between unbalanced and balanced RCTs. We searched the "core clinical journals" of MEDLINE to identify reports of two-parallel group superiority unbalanced RCTs published between January 2009 and December 2010. For each unbalanced RCT, we identified a maximum of four reports (to maximize power) of matched balanced RCTs dealing with the same population. Our primary outcome was the proportion of positive RCTs [i.e., with statistically significant results for the primary outcome (P < 0.05), showing greater efficacy with the new treatment than the control treatment]. RESULTS: We selected 46 reports of unbalanced RCTs and 164 of balanced RCTs; 65.2% unbalanced RCTs and 43.9% of balanced RCTs were positive (odds ratio, 2.38; 95% confidence interval: 1.23, 4.63). As compared with balanced RCTs, unbalanced RCTs were more often industry funded and their control treatments were more often inactive. Adjusting for these latter variables did not modify the results. CONCLUSION: This result questions the respect of clinical equipoise in unbalanced RCTs.

Rationale for unequal randomization in clinical trials is rarely reported: a systematic review.

OBJECTIVES: To assess the reporting of the unequal randomization ratio in reports of trials with this design and to identify the justification for the design. STUDY DESIGN AND SETTING: Systematic review of reports of trials with unequal randomization. We selected all original reports of two parallel-group randomized controlled trials with unequal randomization, which were published in 2009 and 2010 in core clinical journals in MEDLINE on the basis of the abstract (and full text, if necessary). Additional information was collected by an author survey. RESULTS: We retrieved 106 reports (prevalence, 4.7%). The randomization ratio was not stated in 8.5% of reports and 51.9% of abstracts. Sample size calculation was reported in 70 reports, with unequal randomization not taken into account in 25.7% (n = 18). Justification for unequal randomization was not reported in 77.4% (n = 82) of reports. Combining information from reports and author surveys, we had justification for 41 trials. The main justification was safety issues for 20 trials. In 11 of those latter 20 reports, adverse events were not fully reported. CONCLUSION: A better reporting of the randomization ratio, sample size calculation, and justification to unequal randomization could help readers appraise the quality and risk of bias of such trials.

ESCAPE-ancillary blood pressure measurement study: end-digit preference in blood pressure measurement within a cluster-randomized trial.

BACKGROUND: In a cluster-randomized trial including 1832 hypertensive patients, all 126 general practitioners (GPs) in the intervention group (IG) used an oscillometric device that was provided for blood pressure (BP) measurements. Of the 131 GPs of the control group (CG), 24.6% used an oscillometric device (OCG), and 75.4% used a manual device (MCG). At baseline, patients in the IG and CG were comparable for all clinical and biological characteristics, except BP, which was higher in the IG (146/84 vs. 139/81 mmHg; P<0.001). The purpose of this ancillary study was to assess whether these differences in BP values were related to the end-digit preference (EDP), selection bias, or both. METHODS: Analysis was carried out and comparison was made of 3629 BP measurements by 257 GPs. Statistical analysis used hierarchical mixed-effect models with random physician effect and fixed-effect covariables. RESULTS: The frequencies of 0 end digit were 16.7% in the IG, 32.4% in the OCG and 68.8% in the MCG for systolic BP (SBP; P<0.001 for all comparisons), and respectively 17.7, 38.1, and 74.1% for diastolic BP (DBP; P=0.017 for all comparisons). SBP was higher in the IG than in OCG (+3.65 mmHg, P=0.017). The same trend was observed for DBP, though not significant (+1.50 mmHg, P=0.20). The EDP in the CG led to a mean underevaluation of 2.4 mmHg (P<0.0005) of SBP and DBP. CONCLUSION: The observed differences in BP between the groups are partly explained by the impact of EDP. Compared with the manual, oscillometric measurement may reduce EDP.