PRESCRIPTION DRUG USE, ABUSE, AND DIVERSION

NIH GUIDE, Volume 23, Number 21, June 3, 1994



PA NUMBER:  PA-94-070



P.T. 34



Keywords:

  Drugs/Drug Abuse 

  Mental Disorders 

  Pharmaceuticals 



National Institute on Drug Abuse

National Institute of Mental Health



PURPOSE



The purpose of this program announcement is to encourage research on

the use, misuse, abuse, and diversion of prescription psychoactive

medications such as the opioids, stimulants, antipsychotics,

antidepressants, anti-parkinsonism agents, anxiolytics, and

sedative-hypnotics.  Studies on the risk of addiction in patients

being appropriately treated with psychoactive medications

(particularly the analgesics, stimulants, anxiolytics, and

sedative-hypnotics) for acute and chronic medical and psychiatric

illnesses are particularly encouraged.  Studies that assess the risk

of abuse or addiction to prescribed psychoactive medications for

known therapeutic indications in patients with a history of polydrug

abuse are also encouraged.



HEALTHY PEOPLE 2000



The Public Health Service (PHS) is committed to achieving the health

promotion and disease prevention objectives of "Healthy People 2000,"

a PHS-led national activity for setting priority areas.  This program

announcement, Prescription Drug Use, Abuse, and Diversion, is

primarily related to the priority area of alcohol and other drugs.

Potential applicants may obtain a copy of "Healthy People 2000" (Full

Report:  Stock No. 017-001-00474-0, or Summary Report:  Stock No.

017-001-00473-1) through the Superintendent of Documents, Government

Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).



ELIGIBILITY REQUIREMENTS



Applications may be submitted by foreign and domestic for-profit and

non-profit organizations, public and private, such as universities,

colleges, hospitals, laboratories, units of State and local

governments, and eligible agencies of the Federal government.  Women

and minority investigators are encouraged to apply.  Foreign

institutions are not eligible for First Independent Research Support

and Transition (FIRST) (R29) awards.



MECHANISM OF SUPPORT



The mechanisms available for support of this program announcement are

the research project grant (R01), small grant award (R03), and FIRST

award (R29).  Because the nature and scope of the research proposed

in response to this program announcement may vary, it is anticipated

that the size of an award will vary also.



RESEARCH OBJECTIVES



Background



This program announcement is a direct result of a prior request to

the National Institute on Drug Abuse (NIDA) by the Office of National

Drug Control Policy to evaluate the impact of prescription drug

diversion control systems on medical practice and patient care.  In

response to this request, NIDA funded a review of available data and

held two Technical Reviews to identify specific research areas.  This

review presented preliminary evidence that the treatment of patients

with chronic and recurrent illnesses may be adversely affected by

health professionals' fears that patients may abuse or become

addicted to psychoactive medications.  In addition, physicians may

have concerns that regulatory agencies will discipline their

prescribing practices and, as a result, undermedicate patients with

legitimate need.  (Reference, NIDA Research Monograph #131, 1993).

While there is a need to prevent prescription drug abuse and

diversion, this must be balanced with the need to have psychoactive

medications available for legitimate medical and psychotherapeutic

use.



Many anecdotes suggest that drug diversion control programs may

adversely affect patient care.  However, no systematic patient-based

clinical research studies in which prescriptions are related to

therapeutic need and risk of drug dependence are available to

evaluate the merits of these reports.  To evaluate validly and

effectively any changes in prescribing patterns and the impact of

comprehensive prescription drug regulatory mechanisms on patient

care, research is needed that incorporates medical care data about

individual patients and their use of psychoactive medications.

Clinical studies are needed that take into account patients'

histories, diagnoses and treatment, and the clinical appropriateness

or inappropriateness of changes in prescribing practices.  Surveys

are also necessary to determine how attitudes, knowledge, and

patterns of prescribing vary across categories of patients and

prescribers in response to prescription drug control programs.



While existing data suggest that many patients benefit from long-

term therapeutic use of psychoactive medications without evidence of

abuse or addiction, no systematic studies exist either to identify

those at risk of such consequences or to specify practice strategies

best suited for at-risk patients.  A range of research is needed to

develop these strategies--from specifying the extent and nature of

the problem (including health and social consequences) and

identifying their determinants, to discovering effective clinical

practices that identify those at risk and disseminating these

practices to foster more appropriate care.  Research on addiction

risk factors associated with the chronic therapeutic use of

analgesics, stimulants, and sedative-hypnotics for psychiatric and

other medical illnesses is especially needed.  Improved means of

identifying who is at high risk of abusing or becoming addicted to

prescribed psychoactive medications are needed to develop more

effective prevention and intervention strategies.



Program Description



The primary purpose of this program announcement is to stimulate

research on risk factors for abuse and addiction associated with the

therapeutic use of analgesics, stimulants, anxiolytics, and

sedative-hypnotics prescribed for psychiatric and other medical

conditions (e.g., treatment-resistant depression, anxiety, panic

disorder, attention-deficit hyperactivity disorder, obesity,

malignant and non-malignant pain).  Research is encouraged on the

development and use of screening and assessment instruments to assess

conveniently and reliably predictors of addiction in patients being

treated with psychoactive medications for well-established medical

and psychiatric indications.  In addition, research on various

clinical intervention strategies is also encouraged, particularly if

the strategies present some potential for wide dissemination.

Furthermore, studies to evaluate comprehensively the impact of

prescription drug regulatory programs on medical practice and patient

care are especially pertinent to the needs of this program.

Applicants are advised to review existing information relevant to the

Impact of Prescription Drug Diversion Control Systems on Medical

Practice and Patient Care, published in the NIDA Research Monograph

#131, 1993.  Areas of research interest include, but are not limited

to, the following:



o  Discovery of risk factors for abuse and addiction in patients with

chronic or recurring psychiatric or medical conditions who take

psychoactive medications chronically or recurrently.  Obviously, in

this group of patients, dependence upon medications needs to be

distinguished from abuse of or addiction to them, if possible.



o  Clinical studies that assess the risk of abuse or addiction to any

prescribed psychoactive medication for known therapeutic indications

in patients with a history of polydrug abuse.



o  Clinical studies to determine effective clinical practices in the

management of pain or anxiety in substance abusing patients.



o  Studies to develop better screening and assessment instruments for

primary care settings to assess the need for and addictive risk of

analgesics, stimulants, anxiolytics, and sedative-hypnotics in those

patients being treated for medical or psychiatric complaints or

conditions.



o  Surveys of the attitudes that primary care physicians have toward

prescribing psychotropic medications, particularly in relation to

attitudes about use of triplicate forms for prescribing controlled

substances and in relation to attitudes about patients with drug

abuse or psychiatric problems.



o  Detailed, comparative studies of the prescribing habits of various

medical specialties.  Since the populations that various specialties

treat differ, these comparative studies should compare how case mix

may influence the sensitivity and specificity of prescribing

practices in relation to indications for prescribing controlled

medications or for alternative treatments.  Understanding the

separate prescribing practices of internists, pediatricians, family

practitioners, psychiatrists, anesthesiologists, neurologists, and

oncologists is important.



o  Clinical research studies to determine the impact of diversion

control mechanisms on medical practice and patient care, particularly

prospective clinical outcome studies that incorporate prescriber and

patient-level data from records of medical services, prescription

drug utilization, data from health insurance claim files, and patient

and practitioner interviews.  Clinical studies are needed that take

into account patients' histories, diagnoses, treatments and the

clinical appropriateness or inappropriateness of changes in

prescribing practices.



o  Epidemiologic and clinical studies to determine whether some

patient populations may be under- or overmedicated or have difficulty

obtaining adequate treatment with controlled substances as a result

of prescription drug control programs.  Models and instruments that

have been developed to measure patients' satisfaction, quality of

life, and functional status should be included in these studies.



o  Epidemiologic studies that explore the current prevalence of use

of treatments for treatment-resistant depression, anxiety, panic

disorder, attention-deficit hyperactivity disorder, obesity, and

malignant and non-malignant pain.  Alternative treatments include the

use of non-controlled medications, as well as psychotherapeutically

or physically based interventions.  Studies that investigate any

population-based feasibility of using effective and appropriate

treatments that do not involve use of controlled substances are

especially desirable.



o  Additional emphasis must be placed on including minorities and

women of all ages in studies of diseases, disorders, and conditions

that affect them specifically.



o  Policy studies to determine the impact of specific prescription

drug regulatory mechanisms on medical practice and patient care.



o  Development of criteria or standards to be used in case

identification of irresponsible prescribers and study of their use

during case review by prescription drug diversion control systems

(encompasses practice parameters and peer review).



o  Studies of the nature and magnitude of prescription drug diversion

from both licit and illicit sources, the cost of processes involved

in diversion control, reductions in diversion, and related outcomes

resulting from regulatory changes.



o  Cost/benefit studies to determine how prescription drug regulatory

programs affect the balance between preventing diversion and

over-regulating medical prescribing practices.



o  Development and testing of epidemiological systems that utilize

Federal and State data bases and are capable of effectively

monitoring any diversion of pharmaceuticals.  Systems that have the

potential for generalized application in many jurisdictions and

States, and for research purposes additional to monitoring drug

diversion, are especially desirable.



o  Behaviorally based studies of physicians, pharmacists, nurses, and

patients to determine the impact of comprehensive prescription drug

regulatory mechanisms on health care practices, prescribing

behaviors, medication dispensing, and delivered patient care.

Studies of factors influencing prescribing decisions are needed to

develop effective practitioner and patient education programs.



o  Clinical and epidemiological studies of drug-abusing populations

in and out of treatment and in various treatment settings (e.g.,

primary care, emergency rooms) pursuing the objectives:  (1) to

determine the nature, extent, and patterns of abuse of prescription

drugs (including non-controlled drugs); (2) to find the sources of

abused prescription drugs (including "doctor shopping"); (3) to

understand the consequences of prescription drug use, misuse, and

abuse to these individuals and their communities; (4) to assess the

practical consequences of drug diversion to drug-abusing individuals

and their communities; and (5) to estimate the incidence and

prevalence of medical and psychiatric conditions in drug-abusing

populations.



o  Development and evaluation of innovative, skills-based, curricula

in medical education that teaches how to prescribe medications and

treatments appropriately and heightens professional awareness

concerning patients likely to abuse psychoactive drugs.



o  Development of interventions, ranging from one-to-one approaches

to computerized strategies, to change patterns of misprescribing.

Assessment of the stability of improved prescribing and its effects

on patient outcomes would be integral to evaluating an intervention's

utility.



The importance of a sound research plan and qualified research staff

cannot be over-emphasized.  It is recommended that investigators use

the most rigorous methodology consistent with the purposes of the

research.  All applications must address issues of project

feasibility, collaborative arrangements, study design and

methodology, sampling procedures, instrumentation, data collection,

quality control, and data analyses as appropriate.  Since these kinds

of research focus on areas of stigmatization and drug abuse,

investigators should consider carefully how the confidentiality of

patients and physicians will be protected during the course of the

research.



STUDY POPULATIONS



INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN

SUBJECTS



It is the policy of the NIH that women and members of minority groups

and their subpopulations must be included in all NIH supported

biomedical and behavioral research projects involving human subjects,

unless a clear and compelling rationale and justification is provided

that inclusion is inappropriate with respect to the health of the

subjects or the purpose of the research.  This new policy results

from the NIH Revitalization Act of 1993 (Section 492B of Public Law

103-43) and supersedes and strengthens the previous policies

(Concerning the Inclusion of Women in Study Populations, and

Concerning the Inclusion of Minorities in Study Populations), which

have been in effect since 1990.  The new policy contains some new

provisions that are substantially different from the 1990 policies.



All investigators proposing research involving human subjects should

read the "NIH Guidelines For Inclusion of Women and Minorities as

Subjects in Clinical Research", which have been published in the

Federal Register of March 9, 1994 (FR 59 11146-11151), and reprinted

in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume

23, Number 11.



Investigators may obtain copies from these sources or from the

program staff or contact person listed below.  Program staff may also

provide additional relevant information concerning the policy.



APPLICATION PROCEDURES



Applications are to be submitted on the grant application form PHS

398 (rev. 9/91) and will be accepted at the standard application

deadlines as indicated in the application kit.  Application kits are

available at most institutional offices of sponsored research and

from the Office of Grants Information, Division of Research Grants,

National Institutes of Health, Westwood Building, Room 449, Bethesda,

MD 20892, telephone 301/710-0267.  The title and number of the

program announcement must be typed in item 2a of face page of the

application.



FIRST applications must include at least three sealed letters of

reference attached to the face page of the original application.

FIRST applications submitted without the required number of reference

letters will be considered incomplete and will be returned without

review.



The completed original application and five legible copies of the PHS

398 form must be sent or delivered to:



Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



REVIEW CONSIDERATIONS



The Division of Research Grants, NIH, serves as a central point for

receipt of applications for most discretionary DHHS grant programs.

Applications received under this program announcement will be

assigned to an initial review group (IRG) in accordance with

established PHS referral guidelines.  The IRGs, consisting primarily

of non-Federal scientific and technical experts, will review the

applications for scientific and technical merit in accordance with

the standard NIH peer review procedures.  Notification of the review

recommendations will be sent to the applicant after the initial

review.  Applications will receive a second-level review by an

appropriate National Advisory Council, whose review may be based on

policy considerations as well as scientific merit.  Only applications

recommended for further consideration by the Council may be

considered for funding.



AWARD CRITERIA



Applications recommended for further consideration by an appropriate

National Advisory Council will compete for available funds with all

other approved applications assigned to the appropriate Institute.

The following will be considered in making funding decisions:

quality of the proposed project as determined by peer review;

availability of funds; and institute program needs and balance.



INQUIRIES



Written and telephone inquiries are encouraged.  The opportunity to

clarify any issues or questions from potential applicants is welcome.



Direct inquiries regarding the programmatic issues focusing upon

epidemiology or services research on addiction risk in patients being

treated with analgesics, stimulants, anxiolytics and

sedative-hypnotics for chronic medical and psychiatric illnesses and

for studies that assess the risk of abuse or addiction to prescribed

medications in patients with a history of drug abuse to:



Dorynne Czechowicz, M.D.

Division of Clinical Research

National Institute on Drug Abuse

5600 Fishers Lane, Room 10A-12

Rockville, MD  20857

Telephone:  (301) 443-4877



Direct inquiries regarding programmatic issues focusing primarily

upon epidemiology or services research regarding the psychiatric

uses/abuses of anti-psychotic medications, antidepressant medications

(including tricyclic antidepressants, monoamine oxidase inhibitors,

selective serotonin reuptake inhibitors), buspirone and related

medications, and medications used to treat pseudo-parkinsonism to:



Douglas Moul, M.D., M.P.H

Division of Epidemiology and Services Research

National Institute of Mental Health

5600 Fishers Lane, Room 10C-09

Rockville, MD  20857

Telephone:  (301) 443-3774



Direct inquires regarding fiscal issues to:



Gary Fleming, J.D., M.A.

Grants Management Branch

National Institute on Drug Abuse

5600 Fishers Lane, Room 8A-54

Rockville, MD  20857

Telephone:  (301) 443-6710



Diana S. Trunnell

Grants Management Branch

National Institute of Mental Health

5600 Fishers Lane, Room 7C-08

Rockville, MD  20857

Telephone:  (301) 443-3065



AUTHORITY AND REGULATIONS



This program is described in the Catalog of Federal Domestic

Assistance No. 93.279.  Awards are made under authorization of

Section 301 of the Public Health Service Act (42 USC 241) and

administered under PHS policies and Federal Regulations at Title 42

CFR 52 "Grants for Research Projects,"  Title 45 CFR Part 74 and 92,

"Administration of Grants" and 45 CFR Part 46, "Protection of Human

Subjects".  Title 42 CFR Part 2, "Confidentiality of Alcohol and Drug

Abuse Patient Records" may also be applicable to these awards.  This

program is not subject to the intergovernmental review requirements

of Executive Order 12372 or Health Systems Agency review.



Sections of the Code of Federal Regulations are available in booklet

form from the U.S. Government Printing Office.  Grants must be

administered in accordance with the PHS Grants Policy Statement,

(revised 10/90), which may be available from your office of sponsored

research.



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