An Analysis of Regulatory Review Times of Supplemental Indications for Already-Approved Drugs: 1989-1994

Abstract

Food and Drug Administration (FDA) review times for supplemental indications of already-approved new chemical entities (NCEs) were compared to the review times for their associated original indications. The data show that mean supplemental indication review time for NCEs that had supplemental indications approved by the FDA during 1989-1994 was 28.3 months, 3.7 months longer than the mean review time for the original indications associated with those supplemental indications. The hypothesis of a positive mean difference between a drug's supplemental and original indication review times for the period 1989-1994 can be accepted (P = .044). Mean review time for the supplemental indications approved during 1993 and 1994 was 19.2 months, compared to 23.8 months for their associated original indications. Over this period, however, the mean difference between a drug's supplemental and original indication review times did not differ from zero by a statistically significant amount. Regression analysis provided support for the hypothesis that supplemental indications that the FDA has identified as important were reviewed, other things being equal, more quickly than other approved follow-on uses. The review time distributions for important supplemental indications and for their associated original indications, though, did not differ by a statistically significant amount.

Keywords

Supplemental indication Approval time FDA Off-label use User fees

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References

Kessler

. Drug promotion and scientific exchange: the role of the clinical investigator. N Engl J Med. 1991; July 18;325(3):201–203.

Drug advancement and promotion. Talk Paper T91-40. Rockville, MD: Food and Drug Administration, July 18, 1991.

Draft policy statement on industry-supported scientific and educational activities: Food and Drug Administration.

Fed Reg. 1992; November 27:57(229):56412.

Pendergast

. Statement on FDA's regulation of prescription drug promotion. Before the Subcommittee on Regulation, Business Opportunities, and Technology, Committee on Small Business, US House of Representatives. October 12, 1994.

Raiford

Shulman

Lasagna

. Determining appropriate reimbursement for prescription drugs: off-label uses and investigational therapies. Food Drug Law J. 1994;49(1):37–76.

FDA Commissioner Kessler to describe off-label use policy in upcoming medical journal article; supplemental approvals may be based on literature references.

The Pink Sheet. 1992 May 4; 54(18):3–5.

Pediatric use drug labeling NDA supplements due by December 1996 — FDA final rule; agency establishing pediatric subcommittee to track implementation.

The Pink Sheet. 1994 Dec 19; 56(51):3–5.

Spivey

Lasagna

Trimble

. New indications for already-approved drugs: time trends for the new drug application review phase. Clin Pharmacol Ther. 1987;41(4):368–370.

DiMasi

Kaitin

Fernandez-Carol

Lasagna

. New indications for already-approved drugs: an analysis of regulatory review times. J Clin Pharmacol. 1991;31(3):205–215.

10.

Offices of drug evaluation statistical report. Rockville, MD: Office of Management, Food and Drug Administration (various years), 1989–1993.

11.

The NDA pipeline. Chevy Chase, MD: F-D-C Development Corp. (various years), 1989–94.

12.

Drug and device product approvals. Rockville, MD: FOI Services (various issues), Jan 1989-Dec 1994.

13.

Chow

. Tests of equality between sets of coefficients in two linear regressions. Econometrica. 1960;28:591–605.

14.

Second annual performance report: Prescription Drug User Fee Act of 1992: Fiscal year 1994 report to Congress. Rockville, MD, Food and Drug Administration, December 1, 1994.

15.

DiMasi

Hansen

Grabowski

Lasagna

. Cost of innovation in the pharmaceutical industry. J Health Econ. 1991;10(2):107–142.

16.

DiMasi

Hansen

Grabowski

Lasagna

. Research and development costs for new drugs by therapeutic category: a study of the US pharmaceutical industry. PharmacoEcon. 1995; 7(2): 152–169.

17.

Specific requirements on content and format of labeling for human prescription drugs; revision of “pediatric use” subsection in the labeling.

Fed Reg. 1994, December 13;59(238):64240.

18.

Outside reviews of supplemental NDAs could expedite FDA review process — Merck's Scolnick; Kessler announces plans for outside review of devices. The Pink Sheet. 1995 Apr 10;57(15):5–6.

19.

Shulman

Hewitt

Manocchia

. Studies and inquiries into the FDA regulatory process: an historical review. Drug Inf J. 1995;29(2):385–413.

20.

FDA reform proposals under consideration by the 104th Congress. The Pink Sheet. 1995 Jul 10; 57(28):6–7.

21.

Lenard

Epstein

Tollison

Viscusi

Wardell

. A new approach for bringing medical products to market: Interim report. Washington, DC: The Progress and Freedom Foundation; June 19, 1995.

22.

Kassenbaum

. Food and Drug Administration Performance and Accountability Act of 1995: discussion draft. Labor and Human Resources Committee, U.S. Senate. November 3, 1995.

23.

Outside NDA reviews may be feasible with GRP guidelines, CDER's Woodcock indicates; FDA reassessing pharm/tox requirements to ease IND filings.

The Pink Sheet. 1995 Apr 17;57(16):19–20.

24.

Beales

III . Marketing information and pharmaceuticals: new uses for old drugs. In: Competitive strategies in the pharmaceutical industry. Washington, DC: American Enterprise Institute; 1996.

25.

Medical societies could petition FDA for approval of new indications under Senate Labor Committee FDA reform proposal; bill language to be drafted during recess. The Pink Sheet. 1995 Aug 14;57(33):3–4.

26.

PhRMA deregulation of educational materials and journal reprints would rely on definition of peer-reviewed journals to maintain level of scientific discourse. The Pink Sheet. 1995 Jun 19; 57(25):3.

27.

Journal reprints with “reference to” unapproved uses would be allowed under FDA promotion reform; textbook dissemination okay if off-label use not “highlighted.”

The Pink Sheet. 1995 Nov 27;57(58):3.

28.

Beales

III . Economic analysis and the regulation of pharmaceutical advertising. Seton Hall Law Review. 1994;24(3):1370–1398.