Randomized crossover trials are clinical experiments in which participants are assigned randomly to a sequence of treatments and each participant serves as his/her own control in estimating treatment effect. We need a better understanding of the validity of their results to enable recommendations as to which crossover trials can be included in meta-analysis and for development of reporting guidelines.ObjectiveTo evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines.MethodsWe searched MEDLINE, EMBASE, and Cochrane’s CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report.ResultsWe identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a meta-analysis would require further manipulation and assumptions.ConclusionsThe high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials.

Background Roflumilast, a phosphodiesterase 4 inhibitor, was approved for the prevention of COPD exacerbations. It is unclear in which patients roflumilast will have a favorable benefit-harm balance. Our aim was to quantitatively assess the benefits and harms of roflumilast (500 mcg per day) compared to placebo. Methods and Findings We used trial data released by the US Food and Drug Administration to estimate the treatment effects of roflumilast. We used data from observational studies when available to estimate the baseline risks for COPD exacerbations and gastrointestinal, neurological and psychiatric harms associated with roflumilast. Using simulation, we calculated the probability that roflumilast provides net benefit. We examined the impacts of different baseline risks for exacerbations and the severity of exacerbations. We varied weights (i.e., relative importance) for outcomes and treated death as a competing risk in the analyses. The probability that roflumilast provides net benefit approximates 0% across different age categories of men and women with varying baseline risks for exacerbations. Using different weights for outcomes did not change the probability that roflumilast provides net benefit. Only in the sensitivity analysis restricted to the prevention of severe exacerbations there was a probability of >50% that roflumilast provides net benefit if the baseline risk of having at least one severe exacerbation per year exceeds 22%. Conclusions Our results suggest roflumilast only provides net benefit to patients at a high risk of severe exacerbations. Guideline developers should consider different recommendations for COPD patients at different baseline risks for exacerbations.

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Purpose To set priorities for new systematic reviews and randomized clinical trials (RCTs) on the management of primary angle closure (PAC) using clinical practice guidelines and a survey of Asia-Pacific clinicians. Methods We restated the American Academy of Ophthalmology’s Preferred Practice Patterns recommendations for management of PAC into answerable clinical questions. We asked participants at the Asia-Pacific Joint Glaucoma Congress 2010 in Taipei to rate the importance of having an answer to each question for providing effective patient care, using a Likert-type scale and scoring from 0 (not important at all) to 10 (highly important). We identified relevant systematic reviews and mapped the evidence to clinical questions to identify evidence gaps. Results We generated 42 clinical questions. One hundred seventy five individuals agreed to participate in the survey, 132 responded (75.4% response rate) and 96 completed the questionnaire (54.9% usable response rate). Questions rated important include laser iridotomy for the prevention of angle closure in primary angle-closure suspects, further therapies in eyes with plateau iris syndrome after laser iridotomy, and evaluation of the fellow eye in acute angle-closure patients for improving prognosis. Up-to-date and conclusive systematic review evidence was not available for any of the 42 clinical questions. Conclusion We identified high priority clinical questions on the management of PAC, none of which had reliable systematic review evidence available. New systematic reviews and RCTs can be initiated to address these evidence gaps.

BackgroundPatient preferences are key parameters to evaluate benefit-harm balance of statins for primary prevention but they are not readily available to guideline developers and decision makers. Our study aimed to elicit patient preferences for benefit and harm outcomes related to use of statins for primary cardiovascular disease prevention and to examine how the preferences differ across economically and socio–culturally different environments.MethodsWe conducted preference-eliciting surveys using best-worst scaling designed with a balanced incomplete-block design (BIBD) on 13 statins-related outcomes on 220 people in Ethiopia and Switzerland. The participants made tradeoff decisions and selected the most and least worrisome outcomes concurrently from each scenario generated using the BIBD. The design yielded 34,320 implied paired-comparisons and 2860 paired-responses as unit of analysis for eliciting the preferences that were analyzed using a conditional-logit model on a relative scale and surface under the cumulative ranking curve from multivariate random-effects meta-analysis model on a scale of 0 to 1.ResultsThere was high internal consistency of responses and minimal amount of measurement error in both surveys. Severe stroke was the most worrisome outcome with a ceiling preference of 1 (on 0 to 1 scale) followed by severe myocardial infarction, 0.913 (95% CI, 0.889–0.943), and cancer, 0.846 (0.829–0.855); while treatment discontinuation, 0.090 (0.023–0.123), and nausea/headache, 0.060 (0.034–0.094) were the least worrisome outcomes. Preferences were similar between Ethiopia and Switzerland with overlapping uncertainty intervals and concordance correlation of 0.97 (0.90–0.99).ConclusionsOur study provides much needed empirical evidence on preferences that help clinical guidelines consider for weighing the benefit and harm outcomes when recommending for or against statins for primary prevention of cardiovascular disease. The preferences are consistent across the disparate settings; however, we recommend inclusion of more countries in future studies to ensure the generalizability of the preferences to all environments.Electronic supplementary materialThe online version of this article (10.1186/s12872-018-0838-9) contains supplementary material, which is available to authorized users.