Laura Clark

Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial

BACKGROUND Despite effective assessment methods and medications targeting osteoporosis and related fractures, screening for fracture risk is not currently advocated in the UK. We tested whether a community-based screening intervention could reduce fractures in older women. METHODS We did a two-arm randomised controlled trial in women aged 70-85 years to compare a screening programme using the Fracture Risk Assessment Tool (FRAX) with usual management. Women were recruited from 100 general practitioner (GP) practices in seven regions of the UK: Birmingham, Bristol, Manchester, Norwich, Sheffield, Southampton, and York. We excluded women who were currently on prescription anti-osteoporotic drugs and any individuals deemed to be unsuitable to enter a research study (eg, known dementia, terminally ill, or recently bereaved). The primary outcome was the proportion of individuals who had one or more osteoporosis-related fractures over a 5-year period. In the screening group, treatment was recommended in women identified to be at high risk of hip fracture, according to the FRAX 10-year hip fracture probability. Prespecified secondary outcomes were the proportions of participants who had at least one hip fracture, any clinical fracture, or mortality; and the effect of screening on anxiety and health-related quality of life. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN 55814835. FINDINGS 12 483 eligible women were identified and participated in the trial, and 6233 women randomly assigned to the screening group between April 15, 2008, and July 2, 2009. Treatment was recommended in 898 (14%) of 6233 women. Use of osteoporosis medication was higher at the end of year 1 in the screening group compared with controls (15% vs 4%), with uptake particularly high (78% at 6 months) in the screening high-risk subgroup. Screening did not reduce the primary outcome of incidence of all osteoporosis-related fractures (hazard ratio [HR] 0·94, 95% CI 0·85-1·03, p=0·178), nor the overall incidence of all clinical fractures (0·94, 0·86-1·03, p=0·183), but screening reduced the incidence of hip fractures (0·72, 0·59-0·89, p=0·002). There was no evidence of differences in mortality, anxiety levels, or quality of life. INTERPRETATION Systematic, community-based screening programme of fracture risk in older women in the UK is feasible, and could be effective in reducing hip fractures. FUNDING Arthritis Research UK and Medical Research Council.

Allocation concealment in randomised controlled trials: are we getting better?

Laura Clark and colleagues assess the allocation concealment methods in a sample of randomised controlled trial publications

Poor reporting quality of key Randomization and Allocation Concealment details is still prevalent among published RCTs in 2011: a review

RATIONALE, AIMS AND OBJECTIVES Randomized controlled trials (RCTs) are powerful tools; it is essential that these trials are not only conducted rigorously, but reported accurately. The aim of this paper was to describe the reporting quality among a set of RCTs published in 2011 on methodological details essential to judging the adequacy of allocation concealment methods employed. METHODS Medline was searched using the Ovid platform to identify all those RCTs published in January 2011 in core clinical journals. Methodological details in relation to allocation concealment were extracted from the identified RCTs to allow the reporting quality to be assessed. If the information was not available in the paper the corresponding author was contacted. RESULTS Eighty-five papers were identified, 74% (n = 63) endorsed the CONSORT statement. 73% (n = 62) required the author to be contacted for further information. Sequence generation methods were ascertained in 74% of trials, allocation concealment method in 41%, details of who recruited participants and who generated the randomization sequence in 38%. CONCLUSIONS There is evidence to suggest that in 2011 key methodological information relating to allocation concealment is still not reported well in RCTs. Authors and journal editors need to ensure explicit and clear methods are reported in RCTs published.

Important outcome predictors showed greater baseline heterogeneity than age in two systematic reviews

OBJECTIVES An unknown number of randomized controlled trials (RCTs) have their treatment allocation subverted. If such trials are included in systematic reviews, biased results may be used to change policy. To assess whether a systematic review contains subverted trials, a meta-analysis of group differences regarding a baseline variable can be undertaken. In this article, the performance of age with another prognostic variable in detecting selection bias within systematic reviews is compared. STUDY DESIGN AND SETTING Two Cochrane systematic reviews, one of low back pain and one of hip protectors for fracture prevention, were identified. The component RCT texts were obtained, and data were extracted on age, baseline back pain score (low back pain review), and baseline body mass (hip protector review). In this exemplar, we tested for baseline heterogeneity with a fixed-effects meta-analysis. RESULTS Heterogeneity in age between the intervention and control groups was found. The observed heterogeneity increased with baseline back pain and body mass relative to age in each review. CONCLUSION We found that covariates predictive of outcome demonstrate greater heterogeneity than age. However, there were fewer missing data relating to age. Reviewers should consider using age and another prognostic covariate in baseline meta-analyses to check the validity of their results.

Aspirin for Venous Ulcers: Randomised Trial (AVURT): study protocol for a randomised controlled trial

BackgroundVenous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs – it is estimated that the cost of treatment for 1 ulcer is up to £1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is often prolonged and up to one quarter of venous leg ulcers do not heal despite standard care. Two previous trials have suggested that low-dose aspirin, as an adjunct to standard care, may hasten healing, but these trials were small and of poor quality. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established.Methods/DesignAVURT is a phase II randomised double blind, parallel-group, placebo-controlled efficacy trial. The primary objective is to examine whether aspirin, in addition to standard care, is effective in patients with chronic VLUs (i.e. over 6 weeks in duration or a history of VLU). Secondary objectives include feasibility and safety of aspirin in this population. A target of 100 participants, identified from community leg ulcer clinics and hospital clinics, will be randomised to receive either 300 mg of aspirin once daily or placebo. All participants will receive standard care with compression therapy. The primary outcome will be time to healing of the reference ulcer. Follow-up will occur for a maximum of 27 weeks. The primary analysis will use a Cox proportional hazards model to compare time to healing using the principles of intention-to-treat. Secondary outcomes will include ulcer size, pain evaluation, compliance and adverse events.DiscussionThe AVURT trial will investigate the efficacy and safety of aspirin as a treatment for VLU and will inform on the feasibility of proceeding to a larger phase III study. This study will address the paucity of information currently available regarding aspirin therapy to treat VLU.Trial registrationThe study is registered on a public database with clinicaltrials.gov (NCT02333123; registered on 5 November 2014).

Determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease: The DOC study

RATIONALE, AIMS, AND OBJECTIVES Early identification of chronic obstructive pulmonary disease (COPD) results in patients receiving appropriate management for their condition at an earlier stage in their disease. The determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease (DOC) study was a case-finding study to enhance early identification of COPD in primary care, which evaluated the diagnostic accuracy of a series of simple lung function tests and symptom-based case-finding questionnaires. METHODS Current smokers aged 35 or more were invited to undertake a series of case-finding tools, which comprised lung function tests (specifically, spirometry, microspirometry, peak flow meter, and WheezoMeter) and several case-finding questionnaires. The effectiveness of these tests, individually or in combination, to identify small airways obstruction was evaluated against the gold standard of spirometry, with the quality of spirometry tests assessed by independent overreaders. The study was conducted with general practices in the Yorkshire and Humberside area, in the UK. RESULTS Six hundred eighty-one individuals met the inclusion criteria, with 444 participants completing their study appointments. A total of 216 (49%) with good-quality spirometry readings were included in the analysis. The most effective case-finding tools were found to be the peak flow meter alone, the peak flow meter plus WheezoMeter, and microspirometry alone. In addition to the main analysis, where the severity of airflow obstruction was based on fixed ratios and percent of predicted values, sensitivity analyses were conducted by using lower limit of normal values. CONCLUSIONS This research informs the choice of test for COPD identification; case-finding by use of the peak flow meter or microspirometer could be used routinely in primary care for suspected COPD patients. Only those testing positive to these tests would move on to full spirometry, thereby reducing unnecessary spirometric testing.

AVURT: aspirin versus placebo for the treatment of venous leg ulcers – a Phase II pilot randomised controlled trial

BACKGROUND Venous leg ulcers (VLUs) are the most common cause of leg ulceration, affecting 1 in 100 adults. VLUs may take many months to heal (25% fail to heal). Estimated prevalence is between 1% and 3% of the elderly population. Compression is the mainstay of treatment and few additional therapies exist to improve healing. Two previous trials have indicated that low-dose aspirin, as an adjunct to standard care, may improve healing time, but these trials were insufficiently robust. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. OBJECTIVES Primary objective - to assess the effects of 300 mg of aspirin (daily) versus placebo on the time to healing of the reference VLU. Secondary objectives - to assess the feasibility of leading into a larger pragmatic Phase III trial and the safety of aspirin in this population. DESIGN A multicentred, pilot, Phase II randomised double-blind, parallel-group, placebo-controlled efficacy trial. SETTING Community leg ulcer clinics or services, hospital outpatient clinics, leg ulcer clinics, tissue viability clinics and wound clinics in England, Wales and Scotland. PARTICIPANTS Patients aged ≥ 18 years with a chronic VLU (i.e. the VLU is > 6 weeks in duration or the patient has a history of VLU) and who are not regularly taking aspirin. INTERVENTIONS 300 mg of daily oral aspirin versus placebo. All patients were offered care in accordance with Scottish Intercollegiate Guidelines Network (SIGN) guidance with multicomponent compression therapy aiming to deliver 40 mmHg at the ankle when possible. RANDOMISATION Participants were allocated in a 1 : 1 (aspirin : placebo) ratio by the Research Pharmacy, St Georges University Hospitals NHS Foundation Trust, using a randomisation schedule generated in advance by the investigational medicinal product manufacturer. Randomisation was stratified according to ulcer size (≤ 5cm2 or > 5cm2). MAIN OUTCOME MEASURE The primary outcome was time to healing of the largest eligible ulcer (reference ulcer). FEASIBILITY RESULTS – RECRUITMENT 27 patients were recruited from eight sites over a period of 8 months. The target of 100 patients was not achieved and two sites did not recruit. Barriers to recruitment included a short recruitment window and a large proportion of participants failing to meet the eligibility criteria. RESULTS The average age of the 27 randomised participants (placebo, n = 13; aspirin, n = 14) was 62 years (standard deviation 13 years), and two-thirds were male (n = 18). Participants had their reference ulcer for a median of 15 months, and the median size of ulcer was 17.1 cm2. There was no evidence of a difference in time to healing of the reference ulcer between groups in an adjusted analysis for log-ulcer area and duration (hazard ratio 0.58, 95% confidence interval 0.18 to 1.85; p = 0.357). One expected, related serious adverse event was recorded for a participant in the aspirin group. LIMITATIONS The trial under-recruited because many patients did not meet the eligibility criteria. CONCLUSIONS There was no evidence that aspirin was efficacious in hastening the healing of chronic VLUs. It can be concluded that a larger Phase III (effectiveness) trial would not be feasible. TRIAL REGISTRATION Clinical Trials.gov NCT02333123; European Clinical Trials Database (EudraCT) 2014-003979-39. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 55. See the NIHR Journals Library website for further project information.

The impact of lung function case‐finding tests on smoking behaviour: A nested randomised trial within a case‐finding cohort

Increasing awareness of peoples lung health through the use of lung function tests or symptom‐based questionnaires is a potential method to aid smoking cessation. We investigated the impact of case‐finding lung function tests for chronic obstructive pulmonary disease on smoking behaviour.

Randomised controlled feasibility trial of the Active Communication Education programme plus hearing aid provision versus hearing aid provision alone (ACE to HEAR): a study protocol

Introduction Up to 30% of hearing aids fitted to new adult clients are reported to be of low benefit and used intermittently or not at all. Evidence suggests that additional interventions paired with service-delivery redesign may help improve hearing aid use and benefit. The range of interventions available is limited. In particular, the efficacy of interventions like the Active Communication Education (ACE) programme that focus on improving communication success with hearing-impaired people and significant others, has not previously been assessed. We propose that improved communication outcomes associated with the ACE intervention, lead to an increased perception of hearing aid value and more realistic expectations associated with hearing aid use and ownership, which are reported to be key barriers and facilitators for successful hearing aid use. This study will assess the feasibility of delivering ACE and undertaking a definitive randomised controlled trial to evaluate whether ACE would be a cost-effective and acceptable way of increasing quality of life through improving communication and hearing aid use in a public health service such as the National Health Service. Methods and analysis This will be a randomised controlled, open feasibility trial with embedded economic and process evaluations delivered in audiology departments in two UK cities. We aim to recruit 84 patients (and up to 84 significant others) aged 18 years and over, who report moderate or less than moderate benefit from their new hearing aid. The feasibility of a large-scale study and the acceptability of the ACE intervention will be measured by recruitment rates, treatment retention, follow-up rates and qualitative interviews. Ethics and dissemination Ethical approval granted by South East Coast-Surrey Research Ethics Committee (16/LO/2012). Dissemination of results will be via peer-reviewed research publications both online and in print, conference presentations, posters, patient forums and Trust bulletins. Trial registration number ISRCTN28090877.

Scoop pen sub-study-a ‘trial within a trial’ of enclosing a pen in questionnaire mailings to increase response rate

Results Of the 3,789 participants sent a 60-month questionnaire in the pen group, 3,500 (92.4%) returned it compared with 3,462/3,793 (91.3%) in the control group (OR 1.16, 95% CI 0.98 to 1.37, p=0.08). There was evidence of a reduction of the number of reminders required (p=0.02) and the time taken to respond (p=0.01) in the pen group. Some difference was found in the completeness of the primary outcome (p=0.05). The pooled OR of response rates from the meta-analysis was 1.21 (95% CI 1.05 to 1.39, p=0.01).