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 MEDLINE, AVLINE, BIOETHICSLINE,
CANCERLIT, CATLINE, HEALTH, POPLINE and TOXLINE. 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
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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 MED
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
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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 Medicus*. 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
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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
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Thompson DF, Heflin NR. Frequency and appropriateness of
drug prescribing for unlabeled uses in pediatric
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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.