The long march to surrogates of meaningful clinical outcomes in MS trials Are we there yet?

Neurology (Impact Factor: 8.29). 11/2011; 77(18):1658-9. DOI: 10.1212/WNL.0b013e3182364a63
Source: PubMed
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    ABSTRACT: Surrogate markers are often used in clinical trials if too much time or expense is involved to observe the effect of treatment on patient-important outcomes. We wished to estimate the ultimate effects of treatment when randomized trials have addressed only a surrogate marker, and additional, independent studies evaluate the association between the surrogate and the final outcome. We show how to calculate the overall effect of treatment on a final outcome, together with its standard error and confidence interval. The methods are illustrated with data on the effect of therapy on hepatitis B seroconversion, a surrogate marker, and its association with patient-important outcomes (cirrhosis and liver cancer). We find that the effect of treatment on the final outcome may be small even if there are strong associations between treatment and the surrogate and between the surrogate and the patient-important outcome. Apparently, robust treatment effects on surrogates are likely to lead to small and uncertain effects on patient-important outcomes. We should be cautious in advising patients to adopt a therapy when compelling evidence is restricted to its impact on surrogate outcomes, particularly if that therapy may be toxic or otherwise cause harms.
    Journal of clinical epidemiology 05/2012; 65(9):940-5. DOI:10.1016/j.jclinepi.2012.02.012 · 3.42 Impact Factor
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    ABSTRACT: As natalizumab (Tysabri(®); Elan Pharmaceuticals, Inc., Dublin, Ireland) and other disease-modifying drugs are entering the market for multiple sclerosis, the treatment repertoire is expanding beyond the established first-line treatments. This is creating new opportunities but also increasing the uncertainty in the appropriate management of this condition with its considerable societal burden. As a result, economic evaluations are increasingly influential in healthcare decision making. Seven evaluations that included natalizumab have been published to date. They largely report favorable results for this treatment compared with other drugs. However, the models used to reach these conclusions have been subjected to significant debate, owing to limited data availability as well as the methodological complexities and uncertainties in the pharmacoeconomics of multiple sclerosis. This review critically discusses the available evidence based on the cost-effectiveness of natalizumab and uses the data to explain more general issues in the evaluation of similar drugs. The review also suggests how shortcomings in current studies may potentially be addressed in the future.
    Expert Review of Pharmacoeconomics & Outcomes Research 04/2013; 13(2):171-82. DOI:10.1586/erp.13.14 · 1.67 Impact Factor

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