Informing breast cancer patients about clinical trials: a randomized clinical trial of an educational booklet. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses.
To evaluate the impact of an educational booklet on women's knowledge of and willingness to participate in a randomized clinical trial of treatment for breast cancer.
                Women undergoing surgery for newly diagnosed early stage breast cancer were randomized to receive, or not, an information booklet explaining the need for and manner in which randomized trials are conducted.
                Eighty-three women with newly diagnosed early stage breast cancer completed a questionnaire assessing attitudes to random clinical trials (RCTs) and were randomized to receive usual information treatment options provided from their oncologist, or the educational booklet in addition to usual information from their oncologist (42 usual information, 41 booklet). Fewer women who received the clinical trials booklet (40% versus 47%) would consider participating in the hypothetical clinical trial (P = 0.6). Mean knowledge scores increased for both groups; moreover, women who did not receive the booklet showed similar improvements to women who received the booklet [mean difference 0.09, 95% confidence interval (CI) -0.66 to 0.83]. In a multivariate analysis women who would consider participating in the clinical trial were more anxious [odds ratio (OR) 5.9, P = 0.02] had involved lymph nodes (OR 5.8, P = 0.02) and were less influenced by negative aspects of clinical trials (OR 7.7, P = 0.0001). After adjustment for these variables women who received the educational booklet were significantly less likely to consider trial participation (OR 0.22, P = 0.05).
                Educating women about clinical trials in this manner appears ineffective in improving recruitment to RCTs. Women appear to be more influenced by their perception of risk than understanding. This finding has ethical implications for communication of information about RCTs. To explore whether reported methodologic quality affects estimated intervention effects in randomized trials and contributes to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.
                Meta-analyses of randomized trials that included at least one large trial (>/=1000 participants) were included, regardless of the therapeutic area. Eligible meta-analyses were identified through electronic searches and bibliographies of relevant articles.
                Full-length randomized trials.
                Methodologic quality was assessed according to reported randomization, double blinding, and follow-up as separate components and by using the Jadad composite scale.
                Fourteen meta-analyses involving 190 randomized trials from eight therapeutic areas were included. Compared with large trials, intervention effects were exaggerated in small trials with inadequate allocation sequence generation (ratio of odds ratios, 0.46 [95% CI, 0.25 to 0.83]; P = 0.011), inadequate allocation concealment (ratio of odds ratios, 0.49 [CI, 0.27 to 0.86]; P = 0.014), and no double blinding (ratio of odds ratios, 0.52 [CI, 0.28 to 0.96]; P = 0.01). Large trials did not differ significantly from small trials with adequate generation of the allocation sequence, adequate allocation concealment, or adequate double blinding. No association was seen between reported follow-up and intervention effects. The Jadad scale provided no additional information because the scale and the quality components overlapped substantially.
                Inadequate generation of the allocation sequence, allocation concealment, and double blinding lead to exaggerated estimates of intervention benefit and may contribute to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.
There are currently insufficient data to confidently inform clinical practice. The limitations of these studies are plentiful and the risk of bias is high. These trials, however, are invaluable guides for current and future study design. Well conducted randomised trials are possible. Some may be underway. Current practice outside of well designed randomised trials should be clearly justified.