TY - JOUR
T1 - Strength of Validation for Surrogate End Points Used in the US Food and Drug Administration's Approval of Oncology Drugs
AU - Kim, Chul
AU - Prasad, Vinay
N1 - Publisher Copyright:
© 2016 Mayo Foundation for Medical Education and Research
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Objective To determine the strength of the surrogate-survival correlation for cancer drug approvals based on a surrogate. Participants and Methods We performed a retrospective study of the US Food and Drug Administration (FDA) database, with focused searches of MEDLINE and Google Scholar. Among cancer drugs approved based on a surrogate end point, we examined previous publications assessing the strength of the surrogate-survival correlation. Specifically, we identified the percentage of surrogate approvals lacking any formal analysis of the strength of the surrogate-survival correlation, and when conducted, the strength of such correlations. Results Between January 1, 2009, and December 31, 2014, the FDA approved marketing applications for 55 indications based on a surrogate, of which 25 were accelerated approvals and 30 were traditional approvals. We could not find any formal analyses of the strength of the surrogate-survival correlation in 14 out of 25 accelerated approvals (56%) and 11 out of 30 traditional approvals (37%). For accelerated approvals, just 4 approvals (16%) were made where a level 1 analysis (the most robust way to validate a surrogate) had been performed, with all 4 studies reporting low correlation (r≤0.7). For traditional approvals, a level 1 analysis had been performed for 15 approvals (50%): 8 (53%) reported low correlation (r≤0.7), 4 (27%) medium correlation (r>0.7 to r<0.85), and 3 (20%) high correlation (r≥0.85) with survival. Conclusions The use of surrogate end points for drug approval often lacks formal empirical verification of the strength of the surrogate-survival association.
AB - Objective To determine the strength of the surrogate-survival correlation for cancer drug approvals based on a surrogate. Participants and Methods We performed a retrospective study of the US Food and Drug Administration (FDA) database, with focused searches of MEDLINE and Google Scholar. Among cancer drugs approved based on a surrogate end point, we examined previous publications assessing the strength of the surrogate-survival correlation. Specifically, we identified the percentage of surrogate approvals lacking any formal analysis of the strength of the surrogate-survival correlation, and when conducted, the strength of such correlations. Results Between January 1, 2009, and December 31, 2014, the FDA approved marketing applications for 55 indications based on a surrogate, of which 25 were accelerated approvals and 30 were traditional approvals. We could not find any formal analyses of the strength of the surrogate-survival correlation in 14 out of 25 accelerated approvals (56%) and 11 out of 30 traditional approvals (37%). For accelerated approvals, just 4 approvals (16%) were made where a level 1 analysis (the most robust way to validate a surrogate) had been performed, with all 4 studies reporting low correlation (r≤0.7). For traditional approvals, a level 1 analysis had been performed for 15 approvals (50%): 8 (53%) reported low correlation (r≤0.7), 4 (27%) medium correlation (r>0.7 to r<0.85), and 3 (20%) high correlation (r≥0.85) with survival. Conclusions The use of surrogate end points for drug approval often lacks formal empirical verification of the strength of the surrogate-survival association.
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U2 - 10.1016/j.mayocp.2016.02.012
DO - 10.1016/j.mayocp.2016.02.012
M3 - Article
AN - SCOPUS:84973449789
SN - 0025-6196
VL - 91
SP - 713
EP - 725
JO - Mayo Clinic Proceedings
JF - Mayo Clinic Proceedings
IS - 6
ER -