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Ann Neurol. 2009 Aug;66(2):184-90. doi: 10.1002/ana.21676.

Pivotal studies of orphan drugs approved for neurological diseases.

Author information

  • 1College of Physicians and Surgeons, Columbia University, New York, NY, USA. jmm2174@columbia.edu

Abstract

OBJECTIVE:

To identify design elements of clinical trials leading to US Food and Drug Administration approval of drugs for neurological diseases with and without orphan indications.

METHODS:

We used publicly available information to identify approvals for drugs for neurological diseases with an orphan indication (n = 19) and compared them with recent approvals for drugs for neurological diseases without an orphan indication (n = 20). We identified "pivotal trials" from drug labels and drug approval packages, and assessed them on four elements of clinical trial design: control, blinding, randomization, and size.

RESULTS:

All drugs for neurological diseases (100%) approved without an orphan indication included at least two randomized, double-blind, placebo-controlled trials. In comparison, 32% of drugs with an orphan indication had at least two such trials (p < 0.001) and 74% had at least one (p = 0.02). Thirty-three pivotal trials were conducted for the 19 drugs approved with an orphan indication. Of the 33 trials, 11 (33%) did not use a placebo control, 9 (27%) were not double blind, and 4 (12%) were not randomized. Drugs approved without an orphan indication had more pivotal trials per drug (3.8 vs 1.7 trials; p < 0.001) and a larger mean trial size (506 vs 164 trial participants; p < 0.001).

INTERPRETATION:

The US Food and Drug Administration has approved orphan drugs for neurological diseases without randomized, doubled-blind, placebo-controlled pivotal trials. As orphan drug development grows, demand will likely increase for alternative designs for conducting adequate and well-controlled studies to demonstrate drug efficacy.

PMID:
19743448
[PubMed - indexed for MEDLINE]
PMCID:
PMC3785304
Free PMC Article
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