CBM 92-11 Off-Label Use of Prescription Drugs January 1986 through December 1992 103 Citations Prepared by Jacqueline van de Kamp, M.L.S., Specialized Information Services Division U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Library of Medicine Reference Section 8600 Rockville Pike Bethesda, Maryland 20894 1992 SERIES NOTE Current Bibliographies in Medicine (CBM) is a continuation in part of the National Library of Medicine's Literature Search Series, which ceased in 1987 with No. 87-15. In 1989 it also subsumed the Specialized Bibliography Series. Each bibliography in the new series covers a distinct subject area of biomedicine and is intended to fulfill a current awareness function. Citations are usually derived from searching a variety of online databases. NLM databases utilized include MEDLINEþ, AVLINEþ, BIOETHICSLINEþ, CANCERLITþ, CATLINEþ, HEALTH, POPLINEþ and TOXLINEþ. The only criterion for the inclusion of a particular published work is its relevance to the topic being presented; the format, ownership, or location of the material is not considered. Comments and suggestions on this series may be addressed to: Karen Patrias, Editor Current Bibliographies in Medicine Reference Section National Library of Medicine Bethesda, MD 20894 Phone: 301-496-6097 Fax: 301-402-1384 Internet: patrias@nlm.nih.gov Ordering Information: Current Bibliographies in Medicine is sold by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402. To order the entire CBM series for the calendar year 1992 (approx. 14 bibliographies), send $41.00 ($51.25 foreign) to the Superintendent of Documents citing GPO List ID: CBM92. To order the series for 1993 (approximately 7 bibliographies), send $24.00 ($30.00 foreign) citing GPO list ID: CBM93. Orders for individual bibliographies in the series ($3.25, $4.06 foreign) should be sent to the Superintendent of Documents citing the title, CBM number, and the GPO List ID given above. OFF-LABEL USE OF PRESCRIPTION DRUGS Since the early 1960s, the Food and Drug Administration (FDA) has required that drugs used in the United States be both safe and effective. The label information -- on the container, in the package insert, in the Physicians Desk Reference (PDR), and in any advertising -- can indicate a drug's use only in certain "approved" doses and routes of administration for a particular condition. The use of a drug for a disease not listed on the label, or in a dose or by a route not listed on the label, is considered to be a "nonapproved" or "unlabel" or "off-label" use of the drug. Physicians, based on their knowledge and on available current information, may use a drug for a use not indicated in the "approved" labeling if it seems reasonable or appropriate. With the rising costs of health care and the desire to curb these costs, the issue of coverage and reimbursement for the "off-label" use of drugs has become an issue. This bibliography contains selected references to English language publications on the general concept of "off-label" uses of drugs. It includes journal articles, books and book chapters, editorials, and letters to the editor. The NLM wishes to acknowledge the assistance of Drs. Peter Rheinstein and Freddie Ann Hoffman of the Office of Health Affairs, Food and Drug Administration, in final review of this publication. SEARCH STRATEGY A variety of online databases are usually searched in preparing bibliographies in the CBM series. To assist you in updating or otherwise manipulating the material in this search, the strategy used for the NLM's MEDLINE database is given below. Please note that the search strategies presented here differ from individual demand searches in that they are generally broadly formulated and irrelevant citations edited out prior to printing. SS 1 = (TW) OFF AND LABEL SS 2 = TS (TI) :OFF#LABEL: OR :OFF#LABEL: (AB) SS 3 = (TF) ALL UNLABEL: OR UNAPPROVED OR NONAPPROVED SS 4 = 3 AND ALL INDICATION# (TF) OR 3 AND ALL CONDITION# (TF) OR 3 AND ALL DRUG# (TF) OR 3 AND ALL DEVICE# (TF) OR 3 AND ALL REGIMEN# (TF) OR 3 AND ALL MEDICATION# (TF) SS 5 = (TW) ALL PRESCRI: OR APPROVED SS 6 = 5 AND ALL DRUG# (TW) OR 5 AND ALL DEVICE# (TW) OR 5 AND ALL REGIMEN# (TW) OR 5 AND ALL INDICATION# (TW) OR 5 AND ALL CONDITION# (TW) SS 7 = 6 AND UNAPPROVED (TW) OR 6 AND NONAPPROVED (TW) SS 8 = 2 OR 4 OR 7 GRATEFUL MEDþ To make online searching easier and more efficient, the Library offers GRATEFUL MED, microcomputer-based software that provides a user-friendly interface to most NLM databases. This software was specifically developed for health professionals and features multiple choice menus and "fill in the blank" screens for easy search preparation. GRATEFUL MED runs on an IBM PC (or IBM-compatible) with DOS 2.0 or a Macintosh, and requires a Hayes (or Hayes- compatible) modem. It may be purchased from the National Technical Information Service in Springfield, Virginia, for $29.95 (plus $3.00 per order for shipping). SAMPLE CITATION Citations in this bibliographic series are formatted according to the rules established for Index Medicusþ*. A sample journal citation appears below. Journal Article: Authors Article Title Klecker RJ, Cipolle RJ. Procedures for emergency or treatment use of investigational drugs. Am J Hosp Pharm 1987 May;44(5):1086-9. Abbreviated Journal Date Volume Issue Pages Title _________________________________ *For details of the formats used for references, see the following publication: Patrias, Karen. National Library of Medicine recommended formats for bibliographic citation. Bethesda (MD): The Library; 1991 Apr. Available from: NTIS, Springfield, VA; PB91-182030. BIBLIOGRAPHY Abeloff MD. Off-label uses of anticancer drugs [letter]. JAMA 1992 May 13; 267(18):2473-4. Americans want choice to use unapproved drugs. Hosp Formul 1991;26(12):922, 924. APhA supports reimbursement for off-label drug uses. Hosp Formul 1990;25(6):597. Appler WD. The FDA's treatment IND rule - A glimpse into the future of drug regulation in the U.S.? Food Drug Cosmet Law J 1988;43(4):649-58. Appler WD, McMann GL. View from the Nation's Capital. "Off-label" uses of approved drugs: limits on physicians' prescribing behavior. J Clin Psychopharmacol 1989 Oct;9(5):368-70. ASCO supports government report: "Off-label drugs" reimbursement policies constrain physicians in choice of cancer therapies. Oncology (Williston Park) 1991 Oct;5(10): 29-30, 33. Beardsley T. Unapproved drugs for export [news]. Nature 1986 Oct 23-29;323(6090): 657. BLR update: "John and Mary Doe" appeal refusal of request for preliminary injunction: Judge Harris had declined to forbid use of unapproved drugs in Persian Gulf without individual informed consent. Biotechnol Law Rep 1991;10(3):216-7. Blue Cross recommending coverage for off-label drug uses; against routine payment for Treatment INDs. Drug Res Rep Blue Sheet 1989 Nov 1;32(44):2-3. Blue Cross/Blue Shield "can no longer rely" on FDA approval as "adequate evidence" of a drug's efficacy for coverage eligibility -- Blues' Tennenbaum. FDC Rep Pink Sheet 1989 May 1;51(18):14-5. Blue Cross/Blue Shield recommending coverage for off-label drug uses; policy against routine payment for Treatment IND, Group C drugs stands. FDC Rep Pink Sheet 1989 Oct 30;51(44):13-4. Calandra GB, Garelik JP, Kohler PT, Brown KR. Problems and benefits of an antibiotic compassionate therapy program. Rev Infect Dis 1987 Nov-Dec;9(6):1095-101. Cardinale V. Off-label potential of biotech drugs is significant: Huber. Hosp Pharm Rep 1991 Feb;5(2):19. Carey J, Weber J. The FDA is growling at drugmakers, too: It gets tough with companies that promote drugs for unapproved uses. Bus Week 1991 Jul 13; (220):34-5. Charles D. Gulf troops may be guinea pigs for untested drugs. New Scientist 1991 Jan 12;129(1751):23. Cocchetto DM. Issues regarding compassionate treatment with investigational new drugs. Drug Inf J 1989;23(1):87-93. Cohen C, Shevitz A, Mayer K. Expanding access to investigational new therapies. Prim Care 1992 Mar;19(1):87-96. Conlan MF. FDA scrutinizing promotion of unapproved uses. Drug Topics 1991 Jul; 8135(13):53-5. Conlan MF. HHS urged to get moving on off-label cancer uses. Drug Topics 1991 Nov 25;135(22):41. Corrado GC. The export and import of U.S. biopharmaceuticals. Biopharm 1989 Feb; 2(2):18-21. Dangerous `therapies' from abroad. FDA Consumer 1986 Nov;20(9):2-3. de Sousa H. "Unapproved" use of drugs [letter]. Anesth Analg 1987 Apr;66(4): 370. Dickinson J. Bending FDA's marketing rules. Med Mark Media 1990 May;25(5):4, 6, 9. Ereshefsky L. The P and T committee and unlabeled uses of medicines. P T 1991; 16(3):223-4, 229-30, 233-4. Farber MS, Garabedian-Ruffalo SM. Applying drug-use evaluation principles to investigational or unlabeled drug use. Am J Hosp Pharm 1990 Mar;47(3):598-9. FDA encouraging supplemental NDA filings for off-label uses of cancer drugs; agency already has approached two oncology companies, Kessler tells NCAB. FDC Rep Pink Sheet 1992 Feb 3;54(5):8-9. FDA is putting final touches on off-label drugs letter to industry and medical societies; agency seeking information on extent of use, existing research data. FDC Rep Pink Sheet 1992 Jun 15;54(24):7. FDA letters to industry requesting information on unapproved indications will issue "shortly"; NDA supplement backlog has been reduced to 50. FDC Rep Pink Sheet 1992 May 11;54(19):14. FDA standards for cancer approvals are not prime cause of off-label use, Mayo oncologist argues; compendia approach has "shortcomings," GAO says. FDC Rep Pink Sheet 1991 Dec 9;53(49):6-7. FDA watching prescription drug promotion. FDA Consumer 1991 Oct;25(8):2. FDA's Kessler on warpath. Chem Mark Rep 1991 Jun 17;239(24):41. Flannery EJ. Should it be easier or harder to use unapproved drugs and devices? Hastings Cent Rep 1986 Feb;16(1):17-23. Freudenheim M. F.D.A. gets tough on drugs offered for unapproved uses. New York Times 1991 Jun 29;140(48646):1, 9. Gatty B. FDA warns against promoting unapproved drugs, uses. Dermatol Times 1991 Aug;12(8):15. Gebhart F. This off-putting problem of off-label drugs. Hosp Pharm Rep 1991 Apr; 5(4):24-5. General Accounting Office (US). Off-label drugs: initial results of a national survey: briefing report to the chairman, Committee on Labor and Human Resources, U.S. Senate. Washington: The Office; 1991. 27 p. General Accounting Office (US). Off-label drugs reimbursement policies constrain physicians in their choice of cancer therapies: report to the Chairman, Committee on Labor and Human Resources, U.S. Senate. Washington: The Office; 1991 Sep. Report No.: GAO/PEMD-91-14. 59 p. Graham M. The quiet drug revolution. Med Econ 1991 Feb 18;68(4):129-33. Guidance for the emergency use of unapproved medical devices; availability--FDA. Notice. Fed Regist 1985 Oct 22;50(204):42866-7. Haakenson C, Fye CL, Sather MR, Toussaint DJ. The investigator-sponsored IND in clinical trials. Control Clin Trials 1987; 8(2):101-9. Hayman S. BLR update: request denied for preliminary injunction enjoining DoD from using unapproved drugs without individual informed consent. Biotechnol Law Rep 1991;10(2):106-7. HCFA home I.V. Medicare coverage draft list of over 100 drugs includes 14 chemotherapy agents, specifies reimbursable off-label indications. FDC Rep Pink Sheet 1989 May 29;51(22):3-4. HCFA reimbursement for "off-label" uses of approved drugs: Medicare contractors will review reimbursement on a drug- by-drug basis -- HCFA's Buto. FDC Rep Pink Sheet 1989 Mar 20;51(12):9. Higgins LC. Off-label Rx. Insurers starting to balk. Med World News 1988 Oct 24; 29(20):22-4, 26, 31-2. High cost of new biopharmaceuticals triggers reimbursement scrutiny: high manufacturing costs dictate high prices for biopharmaceuticals. Genet Technol News 1992 Apr;12(4):1-2. Howe EG, Martin ED, Annas GJ, Grodin MA, Levine RJ. Treating the troops. Hastings Cent Rep 1991 Mar- Apr;21(2): 21-4. Insurance: the roadblock to providing AIDS care. AIDS Alert 1990 Jan;5(1):1-7. Insurers should reimburse for "off-label" uses of cancer drugs in three standard compendia -- ACCC. Drug Res Rep Blue Sheet 1989 Mar 22;32(12):2-3. James FE. Approved drugs find unapproved uses. Wall Street Journal 1988 Jul 12; 212(7):35. Judge backs Gulf use of unapproved drugs. [news]. New York Times 1991 Feb 1:A9. Kasik JE. Use of approved drugs in a nonapproved way. Iowa Med 1987 Oct; 77(10):513-5. Kempfer L. Minnesota takes stand in extra-label drug use. DVM News Mag 1989 Sep;20(9):1+. Kessler DA. The regulation of investigational drugs. N Engl J Med 1989 Feb 2;320(5): 281-8. Kessler warns about drug, device promotion. FDA Consumer 1991 Sep;25(7):3. Klecker RJ, Cipolle RJ. Procedures for emergency or treatment use of investigational drugs. Am J Hosp Pharm 1987 May;44(5):1086-9. Laetz T, Silberman G. Reimbursement policies constrain the practice of oncology. JAMA 1991;266(21):2996-9. Lasagna L. Practice needs and concerns with regard to unlabeled uses of drugs. P T 1991;16(3):235-6, 238. Lee PP, Yang JC. The nonapproved use of medications. Ophthalmology 1991 Jul; 98(7):1071-4. Levine RJ. AIDS treatment drugs: clinical trials and compassionate use. AIDS Publ Policy J 1987 Spring- Summer;2(2):6-8. Leyland-Jones B, Davies BR, Clagett-Carr K, Shoemaker D, Macfarlane D, Fortner C, O'Dwyer PJ, Sarosy G, Foster BJ, Chun HG, Hoth DF, Rubinstein LV. Patient treatment on a compassionate basis: documentation of high adverse drug reaction rate. Ann Oncol 1992;3(1): 59-62. Lipman AG, Neu HC, Singh BN, Weintraub M. Editors' roundtable: current formulas for P & T Committee success (Part 1). Hosp Formul 1987 Mar;22(3):288-98. Lipman AG, Neu HC, Singh BN, Weintraub M. Editors' roundtable: current formulas for P & T Committee success (Part 2). Hosp Formul 1987 Apr;22(4):373-82. Margolis RE. Investigational new drug regs: icing or cake? Healthspan 1988 Dec;5(11): 25-6. McClung HJ, Kauffman RE. Use of nonapproved drugs in children (12). J Pediatr 1992;120(4I):668-9. McCormack J. Denials limit access to state-of-the-art cancer treatment. Hospitals 1991 Jun 5;65(11):56-7. McIntosh H. Off-label drug coverage tackled by states [news]. J Natl Cancer Inst 1990 Jul 18;82(14):1176-7. Medicare policy on off-label drug coverage. FDC Rep Pink Sheet 1991 Sep 30;53(39): T&G 5-6. Medicare to continue covering Group C but not Treatment IND drugs. FDC Rep Pink Sheet 1991 Jan 14;53(2):T&G 10-1. Medicare will continue covering NCI's Group C but not Treatment IND drugs, HCFA draft rules direct. Drug Res Rep Blue Sheet 1991 Jan 16;34(3):6-7. Merz B. Quicker release of drugs spurs logistical challenges. Am Med News 1990 Mar 2;33(9):2, 9. Moertel CG. Off-label drug use for cancer therapy and national health care priorities. JAMA 1991;266(21):3031-2. Mortenson LE. The off-label debate: a threat to the future of cancer care. Cancer Invest 1991;9(5):597-9. Nightingale SL. Action against illegally promoted, foreign-manufactured, unapproved prescription drugs. JAMA 1992;267(11):1442. Nightingale SL. Unlabeled uses of approved drugs. Drug Inform J 1992 Apr-Jun; 26(2):141-7. Nightingale SL. Use of drugs for unlabeled indications. Am Fam Physician 1986 Sep; 34(3):269. Off-label cancer drugs: increased reimbursement denials reported by oncologists. FDC Rep Pink Sheet 1991 Mar 4;53(9):18. Off-label drug uses, new technology adoption could be financed through a trust fund. FDC Rep Pink Sheet 1989 Jun 5;51(23): T&G 5-6. Off-label use of cancer drugs: oncologists report increased denials for reimbursement -- GAO survey. Drug Res Rep Blue Sheet 1991 Mar 6;34(10):5-6. Oldham RK. Speculations for the 1990s. In: Oldham RK, editor. Principles of cancer biotherapy. New York: Marcel Dekker; 1991. p. 667-74. Oncology drug off-label promotions should be judged by FDA. FDC Rep Pink Sheet 1991 Jul 15;53(28):T&G 13-4. Pier NH. Compassionate release of anti-HIV drugs (II). Lancet 1989;2(8676):1399-400. Pugh MC. Unlabeled uses for approved drugs. Am Druggist 1987 Feb;195:127-8, 130, 133-4. Randall T. FDA scrutinizes `off-label' promotions [news]. JAMA 1991 Jul 3; 266(1):11. Reimbursement denials growing for off-label uses of cancer therapies. Hosp Formul 1991;26(6):446, 448. Reimbursement for unapproved uses could be enhanced if drug labeling cites compendia with off-label indications, PMA's Petricciani tells cancer panel. FDC Rep Pink Sheet 1989 Mar 20;51(12):10. Schwab L. New York legislation mandates some off-label drug coverage [news]. J Natl Cancer Inst 1991 May 1;83(9): 602-3. Serradell J, Patwell JT. Unlabeled drug use patterns in a contemporary outpatient setting. J Pharmacoepidemiol 1991;2(2):19-43. Serradell J, Rucker TD. Prescribing for unlabeled conditions: patient benefit or therapeutic roulette? J Pharm Technol 1990 Jan-Feb;6(1):15-20. Serradell J, Wertheimer AI. Unlabeled indications drug use: an international perspective. Clin Res Pract Drug Reg Affairs 1989;7(1):27-34. Shulman SR, Raiford DS. FDA regulations provide broader access to unapproved drugs. J Clin Pharmacol 1990 Jul; 30(7):585-7. Southwick K. Off-label prescribing spurs hope, conflict. Healthweek 1989 Apr 3; 3(7):1, 34. Staver S. Use unproven therapies - or wait? AIDS doctors weigh harm, value of `underground' drugs. Am Med News 1991 Jul 22;34(27):3-4. Strom BL, Tugwell P. Pharmacoepidemiology: current status, prospects, and problems [editorial]. Ann Intern Med 1990 Aug 1;113(3):179-81. Thompson DF, Heflin NR. Frequency and appropriateness of drug prescribing for unlabeled uses in pediatric patients. Am J Hosp Pharm 1987 Apr;44(4):792-4. Thompson RC. Playing hide and seek with the FDA. FDA Consumer 1987 Apr; 21(3):36-7. Treatment INDs should be reimburseable by Medicare, Rep. Waxman says in coverage rule comments; PMA, AHA, AMA oppose cost-effectiveness criterion. FDC Rep Pink Sheet 1989 Apr 10;51(15):10-1. Wagner M. Hospital pharmacies watch prescriptions as debate rages over `off-label' drug use. Mod Healthc 1992 May 11;22(19):62. Weary PE, Lamberg SI. Approved drugs for unapproved indications: some clouds on the horizon [editorial]. J Am Acad Dermatol 1992 Jul;27(1):133-5. Weber J. An FDA rule that's poor science and poor policy. Bus Week 1991 Dec 9; (3243):36. Weddington WW. Use of unproven and unapproved drugs to treat cocaine addiction [letter]. Am J Psychiatry 1990 Nov; 147(11):1576. Weitzman SA, Marcy T. FDA treatment use regulations: a compassionate response. AIDS Publ Policy J 1987 Spring- Summer; 2(2):22-32. Williams HM. Cancer therapy: reimbursement of new therapeutic technologies. Yale J Biol Med 1992 Mar-Apr;65(2):83-97. Winslow R. Report says health insurers' policies put constraints on treatment of cancer. Wall Street Journal 1991 Dec 4; 218(110):B4.