Current Bibliographies in Medicine 92-11

Off-Label Use of Prescription Drugs

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.

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          Karen Patrias, Editor
          Current Bibliographies in Medicine
          Reference Section
          National Library of Medicine
          Bethesda, MD  20894
          Phone: 301-496-6097
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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
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GRATEFUL MED runs on an IBM PC (or IBM-compatible) with DOS
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$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
  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.