Practices, patients and (im)perfect data - feasibility of a randomised controlled clinical drug trial in German general practices

<p>Abstract</p> <p>Background</p> <p>Randomised controlled clinical (drug) trials supply high quality evidence for therapeutic strategies in primary care. Until now, experience with drug trials in German general practice has been sparse. In 2007/2008, the authors conducted an investigator-initiated, non-commercial, double-blind, randomised controlled pilot trial (HWI-01) to assess the clinical equivalence of ibuprofen and ciprofloxacin in the treatment of uncomplicated urinary tract infection (UTI). Here, we report the feasibility of this trial in German general practices and the implementation of Good Clinical Practice (GCP) standards as defined by the International Conference on Harmonisation (ICH) in mainly inexperienced general practices.</p> <p>Methods</p> <p>This report is based on the experience of the HWI-01 study conducted in 29 German general practices. Feasibility was defined by 1) successful practice recruitment, 2) sufficient patient recruitment, 3) complete and accurate data collection and 4) appropriate protection of patient safety.</p> <p>Results</p> <p>The final practice recruitment rate was 18%. In these practices, 79 of 195 screened UTI patients were enrolled. Recruitment differed strongly between practices (range 0-12, mean 2.8 patients per practice) and was below the recruitment goal of approximately 100 patients. As anticipated, practice nurses became the key figures in the screening und recruitment of patients. Clinical trial demands, in particular for completing symptom questionnaires, documentation of source data and reporting of adverse events, did not agree well with GPs' documentation habits and required support from study nurses. In many cases, GPs and practice staff seemed to be overwhelmed by the amount of information and regulations. No sudden unexpected serious adverse reactions (SUSARs) were observed during the trial.</p> <p>Conclusions</p> <p>To enable drug trials in general practice, it is necessary to adapt the setup of clinical research infrastructure to the needs of GPs and their practice staff. Risk adaption of clinical trial regulations is necessary to facilitate non-commercial comparative effectiveness trials in primary health care.</p> <p>Trial Registration</p> <p>Trial registration number: <a href="http://www.controlled-trials.com/ISRCTN00470468">ISRCTN00470468</a></p

The broad spectrum of unbearable suffering in end of life cancer studied in dutch primary care

<p>Abstract</p> <p>Background</p> <p>Unbearable suffering most frequently is reported in end-of-life cancer patients in primary care. However, research seldom addresses unbearable suffering. The aim of this study was to comprehensively investigate the various aspects of unbearable suffering in end-of-life cancer patients cared for in primary care.</p> <p>Methods</p> <p>Forty four general practitioners recruited end-of-life cancer patients with an estimated life expectancy of half a year or shorter. The inclusion period was three years, follow-up lasted one additional year. Practices were monitored bimonthly to identify new cases. Unbearable aspects in five domains and overall unbearable suffering were quantitatively assessed (5-point scale) through patient interviews every two months with a comprehensive instrument. Scores of 4 (serious) or 5 (hardly can be worse) were defined unbearable. The last interviews before death were analyzed. Sources providing strength to bear suffering were identified through additional open-ended questions.</p> <p>Results</p> <p>Seventy six out of 148 patients (51%) requested to participate consented; the attrition rate was 8%, while 8% were alive at the end of follow-up. Sixty four patients were followed up until death; in 60 patients interviews were complete. Overall unbearable suffering occurred in 28%. A mean of 18 unbearable aspects was present in patients with serious (score 4) overall unbearable suffering. Overall, half of the unbearable aspects involved the domain of traditional medical symptoms. The most frequent unbearable aspects were weakness, general discomfort, tiredness, pain, loss of appetite and not sleeping well (25%-57%). The other half of the unbearable aspects involved the domains of function, personhood, environment, and nature and prognosis of disease. The most frequent unbearable aspects were impaired activities, feeling dependent, help needed with housekeeping, not being able to do important things, trouble accepting the situation, being bedridden and loss of control (27%-55%). The combination of love and support was the most frequent source (67%) providing strength to bear suffering.</p> <p>Conclusions</p> <p>Overall unbearable suffering occurred in one in every four end-of-life cancer patients. Half of the unbearable aspects involved medical symptoms, the other half concerned psychological, social and existential dimensions. Physicians need to comprehensively assess suffering and provide psychosocial interventions alongside physical symptom management.</p

Evaluation of a Theory-Informed Implementation Intervention for the Management of Acute Low Back Pain in General Medical Practice: The IMPLEMENT Cluster Randomised Trial

Introduction: This cluster randomised trial evaluated an intervention to decrease x-ray referrals and increase giving advice to stay active for people with acute low back pain (LBP) in general practice. Methods: General practices were randomised to either access to a guideline for acute LBP (control) or facilitated interactive workshops (intervention). We measured behavioural predictors (e.g. knowledge, attitudes and intentions) and fear avoidance beliefs. We were unable to recruit sufficient patients to measure our original primary outcomes so we introduced other outcomes measured at the general practitioner (GP) level: behavioural simulation (clinical decision about vignettes) and rates of x-ray and CT-scan (medical administrative data). All those not involved in the delivery of the intervention were blinded to allocation. Results: 47 practices (53 GPs) were randomised to the control and 45 practices (59 GPs) to the intervention. The number of GPs available for analysis at 12 months varied by outcome due to missing confounder information; a minimum of 38 GPs were available from the intervention group, and a minimum of 40 GPs from the control group. For the behavioural constructs, although effect estimates were small, the intervention group GPs had greater intention of practising consistent with the guideline for the clinical behaviour of x-ray referral. For behavioural simulation, intervention group GPs were more likely to adhere to guideline recommendations about x-ray (OR 1.76, 95%CI 1.01, 3.05) and more likely to give advice to stay active (OR 4.49, 95%CI 1.90 to 10.60). Imaging referral was not statistically significantly different between groups and the potential importance of effects was unclear; rate ratio 0.87 (95%CI 0.68, 1.10) for x-ray or CT-scan. Conclusions: The intervention led to small changes in GP intention to practice in a manner that is consistent with an evidence-based guideline, but it did not result in statistically significant changes in actual behaviour. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN01260600009853

Strategies for improving patient recruitment to focus groups in primary care: a case study reflective paper using an analytical framework

<p>Abstract</p> <p>Background</p> <p>Recruiting to primary care studies is complex. With the current drive to increase numbers of patients involved in primary care studies, we need to know more about successful recruitment approaches. There is limited evidence on recruitment to focus group studies, particularly when no natural grouping exists and where participants do not regularly meet. The aim of this paper is to reflect on recruitment to a focus group study comparing the methods used with existing evidence using a resource for research recruitment, PROSPeR (Planning Recruitment Options: Strategies for Primary Care).</p> <p>Methods</p> <p>The focus group formed part of modelling a complex intervention in primary care in the Resources for Effective Sleep Treatment (REST) study. Despite a considered approach at the design stage, there were a number of difficulties with recruitment. The recruitment strategy and subsequent revisions are detailed.</p> <p>Results</p> <p>The researchers' modifications to recruitment, justifications and evidence from the literature in support of them are presented. Contrary evidence is used to analyse why some aspects were unsuccessful and evidence is used to suggest improvements. Recruitment to focus group studies should be considered in two distinct phases; getting potential participants to contact the researcher, and converting those contacts into attendance. The difficulty of recruitment in primary care is underemphasised in the literature especially where people do not regularly come together, typified by this case study of patients with sleep problems.</p> <p>Conclusion</p> <p>We recommend training GPs and nurses to recruit patients during consultations. Multiple recruitment methods should be employed from the outset and the need to build topic related non-financial incentives into the group meeting should be considered. Recruitment should be monitored regularly with barriers addressed iteratively as a study progresses.</p

Projection of participant recruitment to primary care research: a qualitative study.

BACKGROUND: Recruitment to clinical trials remains a challenge, particularly in primary care settings. Initial projections of participant recruitment need to be as accurate as possible in order to avoid the financial, clinical and ethical costs of trial extensions or failures. However, estimation of recruitment rates is challenging and often poorly executed, if attempted at all. We used qualitative methods to explore the experiences and views of researchers on the planning of recruitment in this setting. METHODS: Participants had registered accrual to a UK-based primary care research study between April 2009 and March 2012. We conducted nine interviews with chief investigators or study managers, using a semi-structured topic guide. Analysis was conducted using the framework approach. RESULTS: Three themes are presented: 1) the factors affecting recruitment rates, 2) the use of planning techniques, and 3) influences on poor estimation. 1) A large number of factors affecting recruitment rates were discussed, including those relating to the study protocol, the clinical setting and the research setting. Use of targeted mail-outs to invite apparently eligible individuals to participate was preferred in order to eliminate some of the uncertainty in the recruitment rate associated with opportunistic clinician referrals. 2) The importance of pilot work was stressed. We identified significant uncertainty as to how best to schedule trial timelines to maximise efficiency. 3) Several potential sources of bias involved in the estimation of recruitment rates were explored and framed as technological, psychological or political factors. CONCLUSIONS: We found a large number of factors that interviewees felt impact recruitment rates to primary care research and highlighted the complexity of realistic estimation. Suitable early planning of the recruitment process is essential, and there may be potential to improve the projection of trial timelines by reducing biases involved in the process. Further research is needed to develop formal approaches that would be suitable for use in this setting

Compression for preventing recurrence of venous ulcers

BACKGROUND: Up to 1% of adults will have a leg ulcer at some time. The majority of leg ulcers are venous in origin and are caused by high pressure in the veins due to blockage or weakness of the valves in the veins of the leg. Prevention and treatment of venous ulcers is aimed at reducing the pressure either by removing/repairing the veins, or by applying compression bandages/stockings to reduce the pressure in the veins.The majority of venous ulcers heal with compression bandages, however ulcers frequently recur. Clinical guidelines therefore recommend that people continue to wear compression, usually in the form of hosiery (tights, stockings, socks) after their ulcer heals, to prevent recurrence. OBJECTIVES: To assess the effects of compression (socks, stockings, tights, bandages) in preventing the recurrence of venous ulcers. If compression does prevent ulceration compared with no compression, then to identify whether there is evidence to recommend particular levels of compression (high, medium or low, for example), types of compression, or brands of compression to prevent ulcer recurrence after healing. SEARCH METHODS: For this second update we searched The Cochrane Wounds Group Specialised Register (searched 4 September 2014) which includes the results of regular searches of MEDLINE, EMBASE and CINAHL; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8). SELECTION CRITERIA: Randomised controlled trials (RCTs)evaluating compression bandages or hosiery for preventing the recurrence of venous ulcers. DATA COLLECTION AND ANALYSIS: Two review authors undertook data extraction and risk of bias assessment independently. MAIN RESULTS: Four trials (979 participants) were eligible for inclusion in this review. One trial in patients with recently healed venous ulcers (n = 153) compared recurrence rates with and without compression and found that compression significantly reduced ulcer recurrence at six months (Risk ratio (RR) 0.46, 95% CI 0.27 to 0.76).Two trials compared high-compression hosiery (equivalent to UK class 3) with moderate-compression hosiery (equivalent to UK class 2). The first study (n=300) found no significant reduction in recurrence at five years follow up with high-compression hosiery compared with moderate-compression (RR 0.82, 95% CI 0.61 to 1.12). The second study (n = 338) assessed ulcer recurrence at three years follow up and found that high-compression hosiery reduced recurrence compared with moderate-compression (RR 0.57, 95% CI 0.39 to 0.81). Statistically significant heterogeneity precluded meta-analysis of the results from these studies. Patient-reported compliance rates were reported in both trials;,there was significantly higher compliance with medium-compression than with high-compression hosiery in one and no significant difference in the second.A fourth trial (166 patients) found no statistically significant difference in recurrence between two types of medium (UK class 2) compression hosiery (Medi versus Scholl: RR 0.74, 95% CI 0.45 to 1.2).No trials of compression bandages for preventing ulcer recurrence were identified. AUTHORS' CONCLUSIONS: There is evidence from one trial that compression hosiery reduces rates of reulceration of venous ulcers compared with no compression. Results from one trial suggest that recurrence is lower in high-compression hosiery than in medium-compression hosiery at three years whilst another trial found no difference at 5 years. Rates of patient intolerance of compression hosiery were high. There is insufficient evidence to aid selection of different types, brands, or lengths of compression hosiery