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Helfand M, Peterson K. Drug Class Review: Triptans: Final Report Update 4 [Internet]. Portland (OR): Oregon Health & Science University; 2009 Jun.

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Drug Class Review: Triptans: Final Report Update 4 [Internet].

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Methods

Literature Search

To identify relevant citations, we searched Ovid MEDLINE® (1996 to week 4 of January 2009), the Cochrane Database of Systematic Reviews® (2nd Quarter 2008), Database of Abstracts of Reviews of Effects (3rd Quarter 2008), and the Cochrane Central Register of Controlled Trials® (3rd Quarter 2008) using terms for included drugs, indications, and study designs (see Appendix B for complete search strategies). We attempted to identify additional studies through hand searches of reference lists of included studies and reviews. In addition, we searched the US Food and Drug Administration’s Center for Drug Evaluation and Research website for medical and statistical reviews of individual drug products. Finally, we requested dossiers of published and unpublished information from the relevant pharmaceutical companies for this review. All received dossiers were screened for studies or data not found through other searches. All citations were imported into an electronic database (Endnote® version X2).

Study Selection

Selection of included studies was based on the inclusion criteria created by the Drug Effectiveness Review Project participants, as described above. Titles and abstracts of citations identified through literature searches were assessed for inclusion using the criteria below. Full-text articles of potentially relevant citations were retrieved and again were assessed for inclusion. Results published only in abstract form were not included because inadequate details were available for quality assessment.

Data Abstraction

The following data were abstracted from included trials: study design, setting, population characteristics (including sex, age, ethnicity, diagnosis), eligibility and exclusion criteria, interventions (dose and duration), comparisons, numbers screened, eligible, enrolled, and lost to follow-up, method of outcome ascertainment, and results for each outcome. We recorded intention-to-treat results when reported. If true intention-to-treat results were not reported, but loss to follow-up was very small, we considered these results to be intention-to-treat results. In cases where only per-protocol results were reported, we calculated intention-to-treat results if the data for these calculations were available. Data abstraction was performed by one reviewer and was independently checked by a second reviewer.

Validity Assessment

We assessed the internal validity (quality) of trials based on the predefined criteria listed in Appendix C. These criteria are based on the US Preventive Services Task Force and the National Health Service Centre for Reviews and Dissemination (United Kingdom) criteria.17, 18 We rated the internal validity of each trial based on the methods used for randomization, allocation concealment, and blinding; the similarity of compared groups at baseline; maintenance of comparable groups; adequate reporting of dropouts, attrition, crossover, adherence, and contamination; loss to follow-up; and the use of intention-to-treat analysis. Trials that had a fatal flaw were rated poor quality; trials that met all criteria were rated good quality; the remainder were rated fair quality. As the fair-quality category is broad, studies with this rating vary in their strengths and weaknesses: The results of some fair-quality studies are likely to be valid, while others are only possibly valid. A poor-quality trial is not valid; the results are at least as likely to reflect flaws in the study design as a true difference between the compared drugs. A fatal flaw is reflected by failure to meet combinations of items of the quality assessment checklist. A particular randomized trial might receive 2 different ratings, one for effectiveness and another for adverse events.

Appendix C also shows the criteria we used to rate observational studies of adverse events. These criteria reflect aspects of the study design that are particularly important for assessing adverse event rates. We rated observational studies as good quality for adverse event assessment if they adequately met 6 or more of the 7 predefined criteria, fair quality if they met 3 to 5 criteria, and poor quality if they met 2 or fewer criteria.

Included systematic reviews were also rated for quality (see Appendix C). We rated the internal validity based a clear statement of the questions(s); reporting of inclusion criteria; methods used for identifying literature (the search strategy), validity assessment, and synthesis of evidence; and details provided about included studies.Again, these studies were categorized as good when all criteria were met.

The overall strength of evidence for a body of evidence pertaining to a particular key question or outcome reflects the risk of bias of the studies (based on quality and study designs), consistency of results, directness of evidence, and precision of pooled estimates resulting from the set of studies relevant to the question. Strength of evidence is graded as insufficient, low, moderate, or high.

Data Synthesis

We constructed evidence tables showing the study characteristics, quality ratings, and results for all included studies. We reviewed studies using a hierarchy of evidence approach, where the best evidence is the focus of our synthesis for each question, population, intervention, and outcome addressed. Studies that evaluated one triptan against another provided direct evidence of comparative effectiveness and adverse event rates. Where possible, these data are the primary focus. Direct comparisons were preferred over indirect comparisons. Similarly, effectiveness and long-term safety outcomes were preferred to efficacy and short-term tolerability outcomes.

In theory, trials that compare triptans with other drug classes or with placebos can also provide evidence about effectiveness. This is known as an indirect comparison and can be difficult to interpret for a number of reasons, primarily issues of heterogeneity between trial populations, interventions, and outcomes assessment. Data from indirect comparisons are used to support direct comparisons, where they exist, and are used as the primary comparison where no direct comparisons exist. Indirect comparisons should be interpreted with caution.

Quantitative analyses were conducted using meta-analyses of outcomes reported by a sufficient number of studies that were homogeneous enough that combining their results could be justified. In order to determine whether meta-analysis could be meaningfully performed, we considered the quality of the studies and the heterogeneity among studies in design, patient population, interventions, and outcomes. When necessary, indirect meta-analyses were done to compare interventions where there were no head-to-head comparisons and where there was a common intervention across studies. All pooled relative risks and 95% confidence intervals were calculated based on random-effects models using StatsDirect statistical software package Version 2.7.0 (7/7/2008). The Q-statistic was calculated to assess heterogeneity in effects between studies. Otherwise, the data are summarized qualitatively.

Copyright © 2009, Oregon Health & Science University, Portland, Oregon.
Bookshelf ID: NBK47293

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