Issues in comparison between meta-analysis and large trials

Clinical Research Division, Tufts University, Бостон, Georgia, United States
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 04/1998; 279(14):1089-93. DOI: 10.1001/jama.279.14.1089
Source: PubMed


The extent of concordance between meta-analyses and large trials on the same topic has been investigated with different protocols. Inconsistent conclusions created confusion regarding the validity of these major tools of clinical evidence.
To evaluate protocols comparing meta-analyses and large trials in order to understand if and why they disagree on the concordance of these 2 clinical research methods.
Systematic comparison of protocol designs, study selection, definitions of agreement, analysis methods, and reported discrepancies between large trials and meta-analyses.
More discrepancies were claimed when large trials were selected from influential journals (which may prefer trials disagreeing with prior evidence) than from already performed meta-analyses (which may target homogeneous trials) and when both primary and secondary (rather than only primary) end points were considered. Depending on how agreement was defined, kappa coefficients varied from 0.22 (low agreement) to 0.72 (excellent agreement). The correlation of treatment effects between large trials and meta-analyses varied from -0.12 to 0.76, but was more similar (0.50-0.76) when only primary end points were considered. When both the magnitude and uncertainty of treatment effects were considered, large trials disagreed with meta-analyses 10% to 23% of the time. Discrepancies were attributed to different disease risks, variable protocols, quality, and publication bias.
Comparisons of large trials with meta-analyses may reach different conclusions depending on how trials and meta-analyses are selected and how end points and agreement are defined. Scrutiny of these 2 major research methods can enhance our appreciation of both for guiding medical practice.

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Available from: Joseph C Cappelleri, Jan 20, 2015
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    • "This review excluded studies conducted exclusively in pure palliative care settings or inpatients, as this was not the focus of this review. It also excluded studies with fewer than 50 patients because of the high risk of publication bias associated with very small studies [13]. The search included publications between January 1, 1990 till December 31, 2012. "
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    ABSTRACT: Purpose: Increasing interest in the Quality of Life outcomes in cancer patients led to increase implementation of their use in routine clinical practice. The aim of this systemic review is to review the scientific evidence behind recommending the use of quality of life (QoL) scales routinely in outpatient evaluation. Methods: Systematic review for all published randomized controlled trials in English language between January 1, 1990 till December 31, 2012. Out of 487 articles (476 identified by electronic search+11 articles identified by manual search), six trials satisfied the eligibility criteria: (1) the study was a randomized controlled trial (RCT) with randomization of patients or health care providers; (2) the findings of the administered questionnaire or scale (the intervention) were given to health care provider, and compared to standard care with no questionnaire administered (the control); (3) study was conducted in outpatient oncology clinics; and (4) an outcome was measured that related to (i) QoL improvement, (ii) reduction in morbidity, (iii) reduction in stress for the patients, (iv) improvement in communication between patients and health care provider, or (v) improved patient satisfaction. Assessment for the quality of the study was done using the GRADE methodology. Results: Serious methodological issues were affecting most of the trials. Overall the evaluation of the quality of the evidence from these identified trials suggests that there is a weak recommendation to use QoL scales in routine oncology practice to improve communication between physicians and patients. Conclusion: The routine use of such tools in the outpatient settings at improving the patient outcome or satisfaction cannot be recommended based on the available evidence. The potential harm with the excess use of resources needed to implement, collect, store, analyse, and present such data to health care providers should be also considered. Further research and better designed trials is required using recent methodological techniques such as item-response theory based questionnaire and cluster randomization might help to reach an answer to this question.
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    • "These publications have been used to inform clinical practice, to aid teaching, direct health policy, guide future research and to serve as a foundation for practice guidelines.[5] Accordingly, systemic reviews and meta-analyses of high-quality primary studies are the highest level of evidence for issues of prevention and treatment in evidence-based medicine.[6] Indeed, the Oxford Centre for Evidence-Based Medicine ranks meta-analyses as level 1a evidence. "
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    • "Our second hypothesis suggests that trials with larger sample sizes will have higher descriptive validity. In the medical literature, descriptive validity tends to be greater in trials with larger sample sizes (Ioannidis et al. 1998; Kjaergard et al. 2001). One of the reasons behind this argument is that larger trials are generally backed by external funders and can require more rigorous methods of delivery, peerreview processes and the funding of studies allows for careful construction of the randomization design. "
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