Table I.

Accelerated approvals based on intermediate clinical endpoints (top) or biomarker surrogate endpoints (bottom)

Drug	Indication	Date of approval	Accelerated approval/confirmatory study
Accelerated approval based on an intermediate clinical endpoint.
Betaseron	For use in ambulatory patients with relapsing-remitting multiple sclerosis.	7/23/1993	Accelerated approval based on the rate and extent of exacerbations of multiple sclerosis (intermediate clinical endpoint, although the size of the treatment effect was small); and improvements in MRI-measured lesion area (surrogate). Confirmatory study: 4—6 year study using disability as measured by the Kurtzke Expanded Disability Status Scale (EDSS); plus correlation of MR imaging with clinical endpoints.
Remicade	Treatment of moderately to severely active Crohn’s disease.	8/24/1998	Accelerated approval based on “clinical response,” defined as a reduction from baseline in the Crohn’s Disease Activity Index (CDAI) of at least 70 at 4 weeks. CDAI is a research tool used to quantify the status of patients with Crohn’s disease that includes a combination of clinical features (number of stools, abdominal pain, well-being, abdominal mass and other clinical features) in addition to quantitative measures such as amount of anti-diarrheal drug use, hematocrit and body weight. Confirmatory study: Maintaining a sustained clinical outcome (“clinical response” at week 30 and “clinical remission” at week 54) in patients with moderate to severely active Crohn’s disease.
Remodulin	Treatment for pulmonary arterial hypertension.	5/21/2002	Accelerated approval based on a combined exercise (6-minute walk test/Borg score) analysis. Confirmatory study: Time to first occurrence of death, hospitalization for complications of hypertension or other clear evidence of deterioration.
Tysabri	For the treatment of patients with relapsing forms of multiple sclerosis.	11/23/2004	Accelerated approval based on a large therapeutic effect on relapse rate through approximately 13 months of treatment. Confirmatory study: Continue the existing trials into the post-marketing period to confirm the durability of the observed effect at 2 years.
Makena	To reduce the risk of preterm birth.	2/3/2011	Accelerated approval based on a demonstration of delay in delivery. Confirmatory studies: Post-marketing studies to demonstrate improved long-term postnatal outcomes.
Accelerated approval based on a biomarker as a surrogate.
Priftin	Treatment of pulmonary tuberculosis.	6/22/1998	Accelerated approval based on sputum culture status at 6 months. Confirmatory study: Negative sputum culture up to 2 years post-treatment.
Synercid	Treatment of patients with infections associated with vancomycin-resistant Enterococcus faecium (VREF) bacteremia.	9/21/1999	Accelerated approval based on a laboratory measurement of bacteria in the blood. Confirmatory study: Clinical resolution of infection.
Celebrex	To reduce the number ofadenomatous colorectal polyps in familial adenomatous polyposis (FAP), as an adjunct to usual care.	12/23/1999	Accelerated approval based on the % change in the number of colorectal adenomas. Confirmatory study: Reduction in the incidence of FAP-related events (e.g., polypectomy, surgery, cancer, desmoids, death). The sponsor did not demonstrate the link between polyp number and onset of colonic cancer after the allotted time allowed to produce these data; thus, this indication and dose were removed from the label.
Sirturo	Combination therapy in adults with pulmonary multi-drug resistant tuberculosis (MDR-TB).	12/28/2012	Accelerated approval based on sputum culture status at 6 months. Confirmatory study: Resolution of pulmonary tuberculosis.
Ferriprox	Treatment of patients with transfusional iron overload due to thalassemia syndromes.	9/9/2015	Accelerated approval based on a decrease in iron stores for patients with iron overload caused by thalassemia. Confirmatory study: Decrease in transfusion-related adverse events caused by iron overload in the body.