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The Value, Qualification, and Regulatory Use of Surrogate End Points in Drug Development
Author(s) -
Lathia CD,
Amakye D,
Dai W,
Girman C,
Madani S,
Mayne J,
MacCarthy P,
Pertel P,
Seman L,
Stoch A,
Tarantino P,
Webster C,
Williams S,
Wagner JA
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.69
Subject(s) - clinical pharmacology , drug development , clinical trial , intensive care medicine , medicine , surrogate endpoint , psychological intervention , value (mathematics) , outcome (game theory) , risk analysis (engineering) , drug , actuarial science , pharmacology , business , statistics , psychiatry , mathematics , mathematical economics
The acceptance and use of either surrogate end points (SEPs) or efficient clinical end points are associated with greater and more rapid availability of new medicines as compared with disease situations for which clinical end points are inefficient or no surrogates exist. This review of the history of the development, qualification, and acceptance of key SEPs shows that both successes and failures had three key characteristics: (i) apparent biologic plausibility, (ii) prognostic value for the outcome of the disease, and (iii) an association between changes in the SEP and changes in outcome with therapeutic intervention—the three factors recommended for SEPs in the International Conference on Harmonisation's “Statistical Principles for Clinical Trials.” We recommend that only prognostic value be an absolute prerequisite for surrogacy, because therapeutic interventions may not exist a priori , and biological plausibility can be subjective. Ideally, all three of these factors would be traded off against one another in a consistent and transparent risk‐management process. Clinical Pharmacology & Therapeutics (2009); 86 , 1, 32–43 doi: 10.1038/clpt.2009.69