Prospectively screening for eligible patients was inaccurate in predicting patient recruitment of orthopedic randomized trials

Objective

To compare the accuracy of estimates of potential recruitment from a prospective 8-week screening study compared with a retrospective chart review across sites participating in two fracture management trials.

Study Design and Setting

During the planning phase of two large, multicenter, randomized controlled fracture management trials, 74 clinical sites provided estimates of the annual recruitment rate both retrospectively (based on chart reviews) and prospectively. The prospective estimate was generated by screening, for 8 weeks, all incoming patients for eligibility in the concerning trial, without actually enrolling any patient. We compared these prospective and retrospective estimates with one another (for 74 sites in the two trials) and with actual 1-year recruitment rates in the definitive trial (for nine sites in one trial).

Results

There was a median difference of four patients (interquartile range: −14 to 18 patients; P = 0.89) between a center's prospective estimate and its retrospective estimate. Both predictions were overestimations of recruitment in the definitive trial; only 31% (95% confidence interval [CI]: 28, 35) of retrospectively estimated patients, and 31% (95% CI: 27, 35) of prospectively estimated patients were recruited in the definitive trials.

Conclusion

Compared with relatively simple chart reviews, prospectively screening for eligible patients at clinical sites, which is associated with substantial costs, did not result in more accurate predictions of accrual in large, multicenter, randomized controlled trials.     

Cardiac rehabilitation after myocardial infarction. Combined experience of randomized clinical trials

Randomized clinical trials of cardiac rehabilitation following myocardial infarction have typically demonstrated a lower mortality in treated patients, but with a statistically significant reduction in only one trial. To overcome the problem of not being able to detect small but clinically important benefits in mortality in randomized clinical trials of exercise and risk factor rehabilitation after myocardial infarction with small numbers of patients, we carried out a meta-analysis on the combined results of ten randomized clinical trials that included 4347 patients (control, 2145 patients; rehabilitation, 2202 patients). The pooled odds ratios of 0.76 (95% confidence intervals, 0.63 to 0.92) for all-cause death and of 0.75 (95% confidence intervals, 0.62 to 0.93) for cardiovascular death were significantly lower in the rehabilitation group than in the control group, with no significant difference for nonfatal recurrent myocardial infarction. These results suggest that, for appropriately selected patients, comprehensive cardiac rehabilitation has a beneficial effect on mortality but not on nonfatal recurrent myocardial infarction.     

Can we individualize the 'number needed to treat'? An empirical study of summary effect measures in meta-analyses

BACKGROUND: Meta-analyses summarize the magnitude of treatment effect using a number of measures of association, including the odds ratio (OR), risk ratio (RR), risk difference (RD) and/or number needed to treat (NNT). In applying the results of a meta-analysis to individual patients, some textbooks of evidence-based medicine advocate individualizing NNT, based on the RR and the patient's expected event rate (PEER). This approach assumes constant RR but no empirical study to date has examined the validity of this assumption. METHODS: We randomly selected a subset of meta-analyses from a recent issue of the Cochrane Library (1998, Issue 3). When a meta-analysis pooled more than three randomized controlled trials (RCT) to produce a summary measure for an outcome, we compared the OR, RR and RD of each RCT with the corresponding pooled OR, RR and RD from the meta-analysis of all the other RCT. Using the conventional P-value of 0.05, we calculated the percentage of comparisons in which there were no statistically significant differences in the estimates of OR, RR or RD, and refer to this percentage as the 'concordance rate'. RESULTS: For each effect measure, we made 1843 comparisons, extracted from 55 meta-analyses. The random effects model OR had the highest concordance rate, closely followed by the fixed effects model OR and random effects model RR. The minimum concordance rate for these indices was 82%, even when the baseline risk differed substantially. The concordance rates for RD, either fixed effects or random effects model, were substantially lower (54-65%). CONCLUSIONS: The fixed effects OR, random effects OR and random effects RR appear to be reasonably constant across different baseline risks. Given the interpretational and arithmetic ease of RR, clinicians may wish to rely on the random effects model RR and use the PEER to individualize NNT when they apply the results of a meta-analysis in their practice.     

Intellectual property considerations in the development and use of HRQL measures for clinical trial research

As a result of the expanded use of health-related quality of life (HRQL) measures in clinical trial research, a variety of legal and ethical issues have surfaced. These issues can be put in the form of the following questlons: (1) Under what circumstances should access to HRQL measures be restricted? (2) Under what circumstances is it appropriate for the developers of HRQL measures to assert their intellectual property rights to the instruments? (3) Under what circumstances is personal profit from the sale and use of HRQL measures legally and socially appropriate? Access to HRQL research is to be encouraged since this is necessary for this field to progress. However, the need for protection against misuse of ongoing work is real and may justify the assertion of intellectual property rights. HRQL measures developed entirely with public monles should remain in the public domain or be managed for the public good. Instruments developed with private funds or with a mix of public and private funds should be treated in a manner that refiects a fair balance between the rights of the private developer and those of the scientific community and the public. HRQL questionnaires are regularly being refined; such work is costly. Investigators continuing research directly related to instrument refinement might reasonably ask for compensation from those who wish to use their work.     

Symptom and quality of life assessment in urinary disorders]

OBJECTIVES: To identify all available symptom and quality of life questionnaires for men and women with urinary disorders and assess their psychometric properties. METHODS: We systematically reviewed the literature in Medline using the key words urinary disorders, urinary incontinence, bladder, score, quality of life, questionnaire, and psychometric validation. RESULTS: The first search using the terms urinary incontinence and quality of life resulted in 1018 Abstracts. Articles mentioning but not measuring quality of life were not investigated. Questionnaires were selected because their psychometric properties were tested and they assessed how much a person was bothered by urinary symptoms or quality of life specific to urinary disorders. The questionnaires were usually gender specific. Their psychometric value was far from uniform, and, for most, responsiveness was not reported. CONCLUSION: Few quality of life questionnaires are at an advanced stage of validation to be applied in clinical practice. They need to be shorter, responsive and validated in different populations to permit their easy use.     

N of 1 randomized trials for investigating new drugs

Presently, in the process of new drug development, large sample parallel group randomized trials are often begun without the detailed knowledge of optimal dose, most responsive patient group, and optimal outcomes which would be desirable. We propose that randomized trials in individual subjects (N of 1 RCTs) could be used to elucidate these issues at an early stage of drug development. In appropriate conditions N of 1 RCTs can be used to define the rapidity with which a drug begins and ceases its clinical action, the likely range of the optimal drug dose, and the optimal outcomes on which subsequent trials should focus. N of 1 RCTs can also generate initial estimates of the proportion of patients who respond to a new agent and for determining sample size, inclusion criteria, and dosage regimen(s) for subsequent parallel group trials. We provide an example of 14 N of 1 RCTs of amitriptyline in fibrositis that illustrate the ways in which N of 1 RCTs can elucidate these issues. The multiple uses of N of 1 RCTs suggest that the method has immense potential for use in the early phases of drug development programs.     

Evidence-based diagnosis in endocrinology.

In this article we present factors that determine whether one can trust the results of studies that describe the properties of diagnostic tests. We review the ways in which the results of such studies could be presented to the readers and consider factors that determine the value of such reports in one's own clinical practice.