Randomized Trials Analyzed as Observational Studies

Annals of internal medicine (Impact Factor: 17.81). 09/2013; 159(8). DOI: 10.7326/0003-4819-159-8-201310150-00709
Source: PubMed
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    ABSTRACT: Scientific knowledge changes rapidly, but the concepts and methods of the conduct of research change more slowly. To stimulate discussion of outmoded thinking regarding the conduct of research, I list six misconceptions about research that persist long after their flaws have become apparent. The misconceptions are: 1) There is a hierarchy of study designs; randomized trials provide the greatest validity, followed by cohort studies, with case-control studies being least reliable. 2) An essential element for valid generalization is that the study subjects constitute a representative sample of a target population. 3) If a term that denotes the product of two factors in a regression model is not statistically significant, then there is no biologic interaction between those factors. 4) When categorizing a continuous variable, a reasonable scheme for choosing category cut-points is to use percentile-defined boundaries, such as quartiles or quintiles of the distribution. 5) One should always report P values or confidence intervals that have been adjusted for multiple comparisons. 6) Significance testing is useful and important for the interpretation of data. These misconceptions have been perpetuated in journals, classrooms and textbooks. They persist because they represent intellectual shortcuts that avoid more thoughtful approaches to research problems. I hope that calling attention to these misconceptions will spark the debates needed to shelve these outmoded ideas for good.
    Journal of General Internal Medicine 01/2014; 29(7). DOI:10.1007/s11606-013-2755-z · 3.42 Impact Factor
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    ABSTRACT: Although randomized trials and observational studies are used as the evidentiary basis of clinical practice guidelines, they are not always in agreement. Limitations in the process of randomization in the former and the selective referral of patients for treatment as a consequence of clinical "risk stratification" in the latter are underappreciated causes for these disagreements. As a result, neither is guaranteed to correctly quantify treatment benefit. This essay reviews the operational differences between these alternative evidentiary sources and shows how these differences can affect individual clinical decisions, population-based practice guidelines, and national health policy. In conclusion, the process of evidence-based medicine can be improved by independent agencies charged with the responsibility to identify and resolve these differences.
    The American journal of cardiology 02/2014; 113(8). DOI:10.1016/j.amjcard.2014.01.420 · 3.28 Impact Factor
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    ABSTRACT: Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are widely prescribed after kidney transplantation, but evidence for an improvement in outcomes is mixed. A recent trial demonstrated a significantly lower incidence of major cardiovascular events in ACEI-treated recipients. Collaborative Transplant Study data on cardiovascular death during years 2 to 10 after kidney transplantation in patients with a functioning graft were analyzed according to whether ACEI/ARB or other antihypertensive therapy (excluding diuretics) was administered at year 1. Of 39,251 transplants analyzed, 15,250 (38.9%) received ACEI/ARB and 24,001 (61.1%) received other antihypertensive therapy at year 1 after transplantation. The mean duration of follow-up was 5.8 years. During years 2 to 10 after transplantation, cardiovascular death occurred in 918 patients (cumulative incidence=4.7%) with a functioning graft. The rate of cardiovascular death was similar in patients who received ACEI/ARB therapy or other antihypertensive treatment overall and in subpopulations of patients who were considered by the transplant center to be at an increased cardiovascular risk, had no pretransplant risk factors, were aged 60 years and older, were treated for diabetes at year 1, or had serum creatinine of 130 μmol/L or higher at year 1. Multivariable Cox regression analysis confirmed that treatment with ACEI/ARB did not confer a beneficial effect beyond that conferred by other antihypertensive treatments on the cumulative incidence of cardiovascular death during years 2 to 10 (hazard ratio=1.1, P=0.24). This large-scale retrospective analysis of prospectively collected data shows that the rate of cardiovascular death in kidney transplant recipients receiving ACEI/ARB or other antihypertensive medications is virtually identical.
    Transplantation 02/2014; 97(3):310-5. DOI:10.1097/01.TP.0000437672.78716.28 · 3.83 Impact Factor
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