Jill Porthouse

Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care

Abstract Objective To assess whether supplementation with calcium and cholecaliferol (vitamin D3) reduces the risk of fracture in women with one or more risk factors for fracture of the hip. Design Pragmatic open randomised controlled trial. Setting Practice nurse led clinics in primary care. Participants 3314 women aged 70 and over with one or more risk factors for hip fracture: any previous fracture, low body weight (< 58 kg), smoker, family history of hip fracture, or fair or poor self reported health. Intervention Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls, or leaflet only (control group). Main outcome measures Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment, falls, and quality of life (measured with the SF-12). Results 69% of the women who completed the follow-up questionnaire at 24 months were still taking supplements (55% with inclusion of randomised participants known to be alive). After a median follow-up of 25 months (range 18 to 42 months), clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures (odds ratio for fracture in supplemented group 1.01, 95% confidence interval 0.71 to 1.43). The odds ratio for hip fracture was 0.75 (0.31 to 1.78). The odds of a woman having a fall at six and 12 months was 0.99 and 0.98, respectively. Quality of life did not significantly differ between the groups. Conclusion We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture. Registration ISRCTN26118436, controlled trials registry.

A comparison of randomised controlled trials in health and education

Health care and educational trials face similar methodological challenges. Methodological reviews of health care trials have shown that a significant proportion have methodological flaws. Whether or not educational trials have a similar proportion of poor-quality trials is unknown. The authors undertook a methodological comparison between health care and educational trials published since 1990. The authors aimed (1) to assess whether the quality of trial reports in education and health care are similar; and (2) to assess whether trial reporting quality is improving. The characteristics of a sample of trials, published since 1990, were taken from health and educational journals. Trials were assessed using the following quality criteria: rationale for sample size; concealment of allocation; blinded follow-up; use of confidence intervals; adequate sample size. Ninety-six placebo drug trials and 54 non-drug trials published in major general journals were identified. These were compared with 54 trials in specialist health journals and 84 trials in educational journals. No educational trial used concealed allocation or reported the rationale for sample size calculation and only one trial used confidence intervals. There was a trend for the reporting of health care trials to improve with time, whilst the reporting quality of educational trials declined. The authors concluded that poor quality of trial reporting is more prevalent in educational journals than in health care journals.

A systematic review and meta-analysis of randomised controlled trials evaluating interventions in adult literacy and numeracy

This paper reports a systematic review of the trial literature in the field of adult literacy and numeracy. The review was undertaken to investigate the effectiveness of teaching strategies and pedagogies designed to increase adult literacy and numeracy. The objectives were to search for and locate, synthesise and quality appraise all the randomised controlled trials aiming to evaluate interventions in adult literacy and/or numeracy, published between 1980 and 2002. Fifty-nine papers were included in the descriptive map. Twelve papers were included that contained nine randomised controlled trials. All of the trials included in the review were of high quality in the sense that they had adopted an appropriate study design for assessing effectiveness. However, within that study design many of the studies had methodological problems, for example: small sample size and lack of justification of sample size calculation; unclear method of random allocation; high attrition rate and lack of ‘intention to teach’ analysis. There was evidence of publication bias. Pooling three studies that compared teaching against no teaching showed a strong, positive and statistically significant effect on outcome. Two other studies examined the use of computer-assisted instruction (CAI) on literacy among imprisoned adults. Pooling these two studies showed a modest but not statistically significant benefit. There is a dearth of rigorous RCTs in the field of adult literacy and numeracy. The evidence is suggestive of a benefit of adult literacy and numeracy interventions; however, because of the heterogeneity of studies, the precise role of any intervention is uncertain and this finding may be undermined by the presence of substantial publication bias. We recommend that a series of large, well-designed and well-conducted randomised trials should be undertaken in the field of adult literacy and numeracy.

Increasing response rates to postal questionnaires: a randomised trial of variations in design

Objectives: Low response rates to postal questionnaires can threaten the validity of studies by reducing the effective sample size and introducing bias. The identification of methods with which to optimise response rates could, therefore, improve the quality of studies. In an attempt to identify such methods, we undertook a randomised trial of two simple variations in questionnaire design. Methods: Using a 2 × 2 factorial design, we conducted a randomised trial to test two variations in questionnaire design; the questionnaires were printed on either single-sided or double-sided paper and had either a single- or multiple-booklet layout. Using equal random allocation, 3836 women were randomised to receive one of these questionnaires as part of a study investigating risk factors for osteoporotic fractures. Results: One thousand eight hundred and seventy questionnaires were returned, giving an overall response rate of 48.7%. There were no significant differences in the overall response to each of the four questionnaire designs. When the number of responders who completed at least 50% of each of the three sections was identified, it was found that single-booklet questionnaires had a better response than the multiple-booklet questionnaires and that single-sided questionnaires had a better response than double-sided questionnaires. However, these results were not significant at the 5% level. There were no significant differences in the response to questions on the odd (left-hand side) pages for the single- compared with the double-sided questionnaires. Conclusion: As the most cost-effective use of resources, we would advocate the use of double- rather than single-sided questionnaires, and use of a single- rather than multiple-booklet design.

The Need for Randomized Controlled Trials in Podiatric Medical Research

The randomized controlled trial is the most robust method available to evaluate health-care treatments. If podiatric medical practice is to be based on rigorous evidence, then high-quality randomized controlled trials are needed to inform that practice. In this article, we examine the extent to which randomized controlled trials are used in recent podiatric medical research and appraise the quality of those that are available. Using the Cochrane database of all randomized controlled trials in health care, we found only six relevant trials undertaken in podiatric medicine since 1997. These studies were of variable quality. We also discuss the key features of a rigorous trial design. To date, the clinical practice of podiatric medicine is not adequately informed by the best available evidence. We call for more high-quality randomized controlled trials to be undertaken in podiatric medical research.

Regarding the systematic review of hip protectors undertaken by Waldegger et al.

Dear editor, The cost effectiveness analysis of hip protectors reported by Waldegger et al. [1] is heavily influenced by the use of a systematic review of hip protectors undertaken by the authors. The review has a number of shortcomings. First, the review is outdated. The search strategy was completed in May 2001, making the review nearly 2 years old. Whilst there is always an inevitable delay between completing any systematic review and publication, the authors ideally ought to continue updating the review until the latest possible time (e.g., when the paper is undergoing peer review). The consequence of this delay is that the authors have not included a number of individually randomised trials. These include: Cameron et al. [2] (published at the end of 2001), a study of ours published as an abstract (summer 2001 [3]) and now as a full paper [4] and finally, the most recently published data by van Schoor et al. [5]. The data from these larger trials show no beneficial effect of hip protectors. If we combine data from the trials that were available in 2001 (i.e., Cameron et al. and Hildreth et al.) and also a trial by Heikinheimo et al. (present in the Cochrane review [6], but not this one) we note a revised effect size of 0.59, which is no longer statistically significant (95% confidence interval 0.21 to 1.70). It also could be argued that the paper by Hubacher and Wettstein should have been included in the analysis. In that study the allocation mechanism is not clearly described, and the trial could either be a controlled study or a proper randomised controlled trial (RCT). If it is defined as the latter the effect sizes of the meta-analysis would diminish even further (i.e., 0.71, 95% CI 0.42 to 1.20). Therefore, data that were in the public domain before the end of 2001 would have reduced the apparent benefit of hip protectors from individually randomised trials into non-significance. Finally, if we include the latest study by van Schoor et al., the effect size declines still further (0.78 95% CI 0.41 to 1.49). The evidence, therefore, for individually randomised trials is less compelling than suggested in the Waldegger paper. If we turn to the cluster trials, many of these have severe methodological flaws that may make their results unreliable. The Ekman trial [7] has only one cluster allocated to the intervention group. There should be at least three if not four clusters in each treatment arm in order to balance any cluster level co-variates; therefore, at best, this trial is an observational study and should not be included in a meta-analysis of randomised trials. The Kannus trial [8] did not use intention-to-treat analysis and is therefore extremely flawed and susceptible to bias (possibly evidenced by the fact that a 30% reduction in forearm fractures was also observed in the intervention group). Finally, all of the trials included in this review made unit of analyses errors (i.e., randomised at the group level but analysed at the patient level). This error was repeated in the meta-analysis by Waldegger et al. as they used an individual patient meta-analysis, thus giving confidence intervals smaller than they should be. The latest published cluster trial, not included in the review, did use cluster level analysis and appeared to show a benefit of hip protectors (although this was not statistically significant). Nevertheless, this trial by Meyer and colleagues [9] also noted a difference in reported falling between the groups, suggesting that the cluster level intervention may have had an effect on overall fall risk factors rather than the hip protectors being effective per se. In conclusion, if hip protectors were as effective as suggested by Waldegger and colleagues, they would be a relatively cost-effective intervention. Until we have available robust trial data, their effectiveness is still open to doubt. Osteoporos Int (2003) 14: 868–869 DOI 10.1007/s00198-003-1485-1