Full Text HS-92-03


NIH GUIDE, Volume 21, Number 12, March 27, 1992

RFA:  HS-92-03

P.T. 34

  Therapy Evaluation 

Agency for Health Care Policy and Research

Application Receipt Date:  July 15, 1992


The purpose of this announcement is to solicit applications from non-
profit organizations to conduct research on the outcomes of
pharmaceutical therapy.  The Agency for Health Care Policy and Research
(AHCPR) is encouraging innovative and timely health services research
on the effectiveness of pharmaceutical therapy and care.  This Request
for Applications (RFA) is an activity of the research component of the
Medical Treatment Effectiveness Program (MEDTEP) in the Department of
Health and Human Services, to assess the appropriateness and
effectiveness of alternative strategies to prevent, diagnose, treat,
and manage clinical conditions.  P.L. 101-239, which established the
AHCPR in December 1989, refers specifically to the need to study the
appropriate use of prescription drugs.  The RFA benefited from
extensive formal discussion with representatives from government,
academia, and industry.


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 RFA, The
Study of Patient Outcomes Associated with Pharmaceutical Therapy, is
related to the section on "Food and Drug Safety" (Objectives 12.5 and
12.6).  Potential applicants may obtain a copy of "Healthy People 2000"
(Full Report:  Stock No. 017-001-00474-0) or "Healthy People 2000"
(Summary Report:  Stock No. 017-001-00473-1) through the Superintendent
of Documents, Government Printing Office, Washington, DC 20402-9325
(telephone 202-783-3238).


Applications may be submitted by domestic and foreign non-profit
organizations, public and private, including universities, clinics,
units of State and local governments, non-profit firms, and non-profit
foundations.  For-profit institutions are not eligible for AHCPR
grants.  Applications from women members of minority population groups
are encouraged.


This RFA will use the research grant mechanism (R01).  Responsibility
for the planning, direction, and execution of the proposed project will
be solely that of the applicant.

This RFA is a one-time solicitation.  If the AHCPR determines that
there is a sufficient continuing program need, the AHCPR may announce
a request for new and competitive continuation applications.  The total
project period for applications submitted in response to this RFA may
not exceed five years.  The continuation of each awarded project will
depend on an annual progress review by the AHCPR and the availability
of funds.


The AHCPR expects to commit up to $3 million in competitive awards for
outcomes research associated with pharmaceutical therapy in Fiscal Year
1993.  Approximately six to ten awards are expected to be made, at the
earliest, in February 1993.  The issuance of awards will be contingent
on the availability of funds and the quality of the applications.


The enabling legislation for the AHCPR (P.L. 101-239) authorizes the
study of the appropriateness and effectiveness of the use of services
and procedures in the prevention, diagnosis, treatment, and management
of clinical conditions.  Priority is given to the study of conditions
and treatment strategies that affect large numbers of people; that
result in substantial expense; that are important in the Medicare and
Medicaid programs; and for which there are significant variations in
patterns of care, implying uncertainty of effectiveness.  The law
recognizes drug therapy as an important form of treatment and refers
specifically to the need to investigate the appropriate use of
prescription drugs.  The purpose of this RFA is to encourage studies on
the patient outcomes of pharmaceutical therapy as part of the ongoing
work supported under MEDTEP.

The Food and Drug Administration (FDA) requires pharmaceutical
manufacturers to provide evidence of safety and efficacy as a condition
for the marketing of drugs.  The FDA's laws and regulations for drug
approval do not contain a requirement for studies of comparative drug
effectiveness (although comparison with a control, which is often a
placebo but may be an active drug, is required to demonstrate
efficacy), alternative therapies (e.g., drug versus surgery), or cost.
The FDA may require comparative studies of drug safety.

An approved drug may enter the market with relatively little
information available for the practitioner, the third party payer, or
the patient about how the drug compares with the array of other
therapies available.  The same indication may be shared by a multitude
of drugs or classes of drugs.  Serious, but rare, adverse reactions, as
well as unique benefits, may remain unknown at the time the drug is
introduced into the market.  After marketing, especially after the
expiration of a product's patent, there may be limited incentive for
continued study of the positive or negative effects of the drug
relative to other competing products or other competing treatment
modalities (including non-treatment).

Patient outcomes research has been driven by the increasing need for
information on appropriateness and effectiveness, as the number of
alternative clinical strategies and related costs increase. Relatively
new methods, such as decision analysis, meta-analysis, and small area
analysis of practice variations, have emerged as major contributors to
the study of patient outcomes.  Research designs and approaches
suitable for the analysis of large computerized claims databases, and
other secondary and primary data sources, have been further developed,
as have tools and instruments that facilitate the measurement and
comparison of risks, benefits, costs, and patient preferences.  This
methodological and design work, however, is in its infancy with regard
to the study of the outcomes of pharmaceutical treatment and care.

In order to generate information useful for the development of an
agenda on this area of outcomes research, AHCPR convened a series of
meetings with representatives from government, academia, and industry.
Many sessions with groups and individuals with expertise in
drug-related research and policy resulted in a list of topics
recommended for study.  This list was categorized into five general
research areas:

o  drug utilization review
o  pharmacists' cognitive services
o  patient factors
o  data and information needs
o  research methods

This RFA emphasizes the relationship between prescription drugs,
pharmaceutical services, and patient outcomes in ambulatory care
settings.  Of particular importance is the need to increase the
availability and the use of data and empirical methods in all areas of
research on the outcomes of pharmaceutical therapy.

For this RFA, the original five categories were aggregated into three
general areas of research:

o  data and analytic methods
o  factors affecting the appropriateness of prescribing
o  the role of the patient

These areas are described below, including sample questions for
research.  The issues and questions raised, however, are illustrative
only, and other study topics relevant to this RFA are welcome.

Data and Analytic Methods

There is a critical need for comprehensive, comparative assessment of
the appropriateness and effectiveness of alternative pharmaceutical
therapies.  Current state-of-the-art methodology for the study of
marketed drugs includes the use of large, linked, administrative
databases (e.g., those used by Medicaid programs); non-randomized,
Phase IV studies (e.g., post-marketing studies by pharmaceutical
firms); registries of adverse events (e.g., the FDA Adverse Drug
Reaction Reporting System); and multi-center, large-scale clinical
trials (e.g., the NIH Cardiac Arrhythmia Suppression Trials).  There
are few comprehensive evaluations of the validity, reliability,
sensitivity/specificity, and generalizability of findings from
post-marketing data.

In order to study alternative pharmaceutical therapies, researchers
should consider using existing data collected for either administrative
or research purposes.  Examples of data sources include State Medicaid
program data, computerized medical and pharmacy records found in
managed care settings, and data recorded in long-term clinical trials.
These sources can be supplemented with primary data collection.

Data sources should allow for the detection, measurement, and/or
control of:  drug exposure, indication for drug use, severity of
illness, co-morbidities, relevant confounders, and the actual costs of
care.  Appropriate outcomes measures and pre-treatment health status
information are required.  Emphasis is to be given to the study of
clinical conditions that meet the following criteria:

o  the predominant mode of therapy is pharmaceutical;
o  a large number of patients are affected;
o  the use of health care resources is substantial, especially for
Medicaid and/or Medicare beneficiaries; and
o  a variety of therapeutic choices exist.

Examples of clinical conditions relevant for study include:
cardiovascular disease; asthma and allergies; bacterial infections;
psychiatric conditions; endocrine diseases; and arthritis.  However,
studies of any conditions treated in an ambulatory care setting that
meet the above criteria are welcome.  The AHCPR encourages studies of
the following:

o  What is the feasibility of using and/or developing comprehensive
databases to address questions concerning the outcomes of
pharmaceutical therapy?  How can multiple data sources, such as
insurance claims for medical and pharmaceutical services and other
administrative records linked for research purposes, provide valid
measures of drug exposure and outcomes?  Which methodological
approaches can be used to increase the utility of these data sources?
What additional information is needed to complement information from
these sources in order to address hypotheses on relationships between
alternative therapies and patient outcomes?

o  In order to relate drug therapy to specific patient outcomes, the
accurate ascertainment of drug exposure is essential.  Markers or
surrogate measures of drug exposure are often used (e.g., numbers of
prescriptions filled).  How valid are currently used measures of drug
exposure at the individual and/or population level?

o  Current therapeutic practice frequently includes pharmacological
treatment to achieve surrogate clinical endpoints.  The example often
cited where treatment and surrogate measures have been linked with
outcomes successfully is the treatment of hypertension for the
prevention of stroke and myocardial infarction.  For other clinical
conditions, how can the association between pharmaceutical treatment to
achieve surrogate endpoints and patient outcomes be validated?

o  Evaluation of the cost effectiveness of a drug therapy is not
required for FDA's approval to market drugs in the United States.  The
results from cost-effectiveness studies are used in drug advertising
and in third-party reimbursement decisions.  However, the relative
technical quality and objectivity of cost- effectiveness analyses have
been questioned.  Separate economic analyses of the same interventions
can lead to very different conclusions because of differences in
methodology.  In addition, because of inter-study methodological
differences, it is difficult to compare the cost effectiveness or net
benefits of a variety of interventions examined in separate studies,
limiting the usefulness of cost-effectiveness analyses for
policymakers.  The process of developing a standard methodology
requires that comparisons between various approaches be undertaken, and
that they be evaluated using patient outcomes as an indicator of the
appropriateness of the tool.  Comparative cost-effectiveness studies
that can be used by the industry and research community as models or
standards for analysis would be especially useful.  What are the
conceptual and methodological issues that merit attention in
comparative cost-effectiveness studies of alternative drug therapies?

o  In some countries (e.g., Canada and the United Kingdom) there are
computerized databases that record drug utilization for the entire
population.  What hypotheses about the outcomes associated with
pharmaceutical therapy can be tested using these international sources
of data?

Factors Affecting the Appropriateness of Drug Prescribing

Previous studies have explored the effects of policy and educational
interventions on the appropriateness of drug prescribing.  For example,
Soumerai (1991) reported that the imposition of a cap on the number of
Medicaid prescriptions per month, per patient increased the number of
admissions to long-term care facilities.  Bloom (1985) demonstrated
that hospital admissions for ulcer disease rose when the State Medicaid
program reduced access to H-2 antagonists.  Shaffner (1983) documented
the relative success of academic detailing in discouraging the
prescribing of tetracycline for children.  Many questions remain,
however, about the long-term effects of private and public programs
that monitor and intervene in the prescribing process.  Existing and
new programs need to be evaluated to determine whether or not they
actually affect patient outcomes.

The AHCPR is interested in new research on the effects on patient
outcomes of programs designed to improve the appropriateness of drug
prescribing.  Examples of these studies include assessment of drug
utilization review (DUR) programs within States or health maintenance
organizations (HMOs); analysis of the relationships among pharmacists'
cognitive services, prescriber behavior, and patient outcomes; and the
comparative long-term success of academic detailing or other
educational interventions aimed at the health care provider in the
managed care setting.

Emphasis will be placed on studies involving existing programs that
have available a comprehensive, longitudinal database including
generalizable patient information, diagnostic data, and data on the use
of prescription drugs.  Primary data collection can be used to augment
existing data sources and to develop and evaluate patient outcomes data
that combine objective and subjective measures, and may be necessary to
validate existing information.

The AHCPR encourages studies of the following:

o  Drug utilization review refers to programs that are expected to
assess and promote the quality of pharmaceutical therapy, minimize
unnecessary expenditure, and intervene whenever inappropriate choice or
actions have been identified.  The Omnibus Budget Reconciliation Act of
1990 requires State Medicaid programs to implement a comprehensive DUR
program by January 1, 1993.  The DUR program is to have a prospective
component in which pharmacists monitor drug therapy; a retrospective
component in which previous patterns of inappropriate drug prescribing
are identified; and an educational component in which health care
providers are targeted for remedial action.  Each State is required to
develop explicit criteria for use by Medicaid DUR programs.  Of
particular interest for this RFA are questions dealing with the linkage
between DUR and patient outcomes in this authorized Medicaid program
and other DUR programs in the private ambulatory care setting.  What is
the effect of variation in drug prescribing patterns on patient
outcomes?  Are differences in the criteria used for monitoring quality
of pharmaceutical therapy associated with different outcomes?  What
specific therapeutic issues should DUR focus on to optimize the
clinical and cost effectiveness of the review process?

o  The Omnibus Budget Reconciliation Act of 1990 also authorizes
demonstrations of the cost effectiveness of pharmacists' cognitive
services for Medicaid recipients.  These services involve the use of
specialized knowledge by the pharmacist to maintain or improve the
quality of drug therapy.  Examples of pharmacists' cognitive services
include patient counseling and education; provider education; the
monitoring of medication profiles and compliance; the development and
enforcement of formularies; and the detection and correction of
prescribing errors.  While demonstrations are not within the scope of
this RFA, several evaluative questions are appropriate for study.  The
focus of these questions should be on the relationships between the
provision of pharmaceutical care, including cognitive services, the
appropriateness of prescribing behavior, and patient outcomes.  How do
organizational, legal/regulatory, reimbursement, and other market or
system factors affect the type and level of available services, the
pattern of prescribing behavior, and related patient outcomes?  What
are the data needs and problems involved in designing and implementing
databases for evaluating the cost effectiveness of cognitive services?

o  Interventions to change prescribing behavior range from face-to-face
academic detailing to less costly computer-generated messages and
letters with specific prescribing information.  Further study of the
effects of these interventions on prescribing behavior and on patient
outcomes is needed.  What are the level and duration of these effects?
Can varying the setting, mechanism, or targeted population lead to more
cost-effective interventions?

The Role of the Patient

Therapeutic goals are condition- and patient-specific, and desired
outcomes will vary by disease, severity of illness, consequences of
therapy, and associated treatment costs.  In addition to objectively
measured consequences of treatment, such as morbidity, mortality, and
hospital readmissions, outcomes of importance include subjective
measures of the patients' quality of life, satisfaction, and perceived
functional status.  Both provider and patient perspectives, including
patient preferences, need to be considered in defining optimal
treatment and outcomes.

Studies on the medication-taking behavior of patients typically focus
on self-care and compliance with a prescribed regimen, with little or
no attention to outcomes.  Self-treatment includes self-diagnosis, home
remedies, over-the-counter (OTC) medications, and often the use of
prescribed medications obtained through unconventional sources (e.g.,
shared by a friend or relative).  Estimates of patient compliance or
cooperation with a prescribed regimen range from thirty to eighty
percent, varying by medical condition, data source, and measures used.
Many tools and strategies have been devised to increase patient
compliance, but the effects on outcomes have not been evaluated.

The AHCPR is interested in studies that will address the following:

o  How does patient compliance with a prescribed drug regimen vary with
respect to changes in perceived quality of life and functional status,
controlling for factors such as access to care and costs of care?  How
do organizational and administrative barriers (e.g., waiting lists,
lack of continuity of care) affect patient outcomes?  To what extent do
health care provider services such as counseling and medication profile
monitoring affect patient outcomes?  How does this effect vary by type
of provider (e.g., physician, nurse, or pharmacist) and by patient
characteristics (e.g., sociodemographic, economic, and behavioral)?

o  For many conditions, objective indicators are the primary choice for
measuring patient outcomes.  For other conditions, for which objective
measures are less precise, subjective measures, such as quality of life
and patient satisfaction, may be more appropriate indicators of
effectiveness.  What is the association between objective and
subjective measures for specific conditions?  How can both types of
measures be used in conjunction with existing administrative databases
to improve the analysis of comparative effectiveness of alternative

o  To what extent can existing databases or new primary data be used to
examine the relationship between self-care and patient outcomes?  What
are the factors that motivate self-care, and how are outcomes
differentially affected by this practice versus the use of a prescribed

o  Models and instruments have been developed to measure patient
satisfaction, quality of life, functional status, and utility.  To what
extent can these tools be used to compare outcomes among alternative
pharmaceutical therapies?  What analytical tools and instruments are
most effective in measuring patient preference, knowledge, and
practices with respect to drug therapy?


Applications should specifically address the appropriateness and/or
effectiveness of pharmaceuticals or related services.  Appropriateness
signifies care for which the benefit (or probability of benefit)
exceeds the negative consequences (or risk) by an acceptable margin.
Effectiveness refers to the results of clinical interventions provided
in typical, "real world" patient-provider situations, in contrast to
the controlled, "laboratory" settings in which efficacy may be

Projects should include investigator(s) and key staff who reflect the
multidisciplinary nature of outcomes research, including, as
appropriate:  health care providers, such as physicians, pharmacists,
nurses, physical therapists, and relevant specialists; health services
researchers; statisticians, biostatisticians, and epidemiologists; and
individuals whose expertise includes health economics, policy, and/or
decision theory.


The AHCPR adheres to NIH and ADAMHA policy that requires applicants for
research grants and cooperative agreements to include minorities and
women in study populations, so that research findings can be of benefit
to all persons.  Additional emphasis, however, must be placed on the
need to include minorities and women of all ages in studies of
diseases, disorders, and conditions that affect them specifically.  If
minorities or women are excluded or inadequately represented in
proposed health services research, particularly in proposed
population-based studies, a clear compelling rationale must be

The composition of any proposed population group for study must be
described in terms of gender and racial/ethnic group.  In addition,
gender and racial/ethnic issues must be addressed in developing a
research design and sample size appropriate for the scientific
objectives of the study.  This information must be included in the form
PHS 398 in Section 2, 1-4 of the Research Plan and summarized in
Section 2, E, Human Subjects.

All applications for outcomes research associated with pharmaceutical
therapy submitted to the AHCPR are required to address this policy with
respect to the inclusion of minorities and women as subjects of their
research.  The AHCPR will not award grants for applications that do not
comply.  If the required policy is not reflected in the application,
the application will be returned without review.


The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  State and local government agencies may
use form PHS 5161 and follow those requirements for copy submission.
These forms are available from:

Office of Scientific Review
Agency for Health Care Policy and Research
2101 East Jefferson Street, Suite 602
Rockville, MD  20852
Telephone:  (301) 227-8449

The RFA label available in the PHS 398 application form must be affixed
to the bottom of the face page of the application.  Failure to use this
label could result in delayed processing of the application such that
it may not reach the review committee in time for review.  In addition,
the RFA title and number must be typed on line 2a of the face page of
the application form and the YES box must be marked.

The completed original, signed application and four legible copies of
PHS form 398 must be sent or delivered to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

Completed applications must be received at the Division of Research
Grants on or before the receipt date specified in this announcement.

One copy labeled "Advance Copy" is to be submitted simultaneously to:

Center for Medical Effectiveness Research
Agency for Health Care Policy and Research
2101 East Jefferson Street, Suite 605
Rockville, MD  20852

Conference for Prospective Applicants

The AHCPR plans to convene a conference in Chicago on April 20, 1992.
At this conference, AHCPR staff will discuss the programmatic and
administrative details of this RFA and respond to questions concerning
this announcement.  Attendance is not a prerequisite for applying.
Individuals with questions concerning this announcement, or unable to
attend the conference, may call or write the AHCPR staff members listed
below for further technical and/or administrative assistance.  The
AHCPR will make available to interested parties a listing of key
questions and answers concerning the program that are addressed at the
conference.  Those interested in attending the conference should
forward their addresses and telephone numbers to Drs. Bosco or Perfetto
at the address listed below under INQUIRIES.  The AHCPR will inform
interested parties of the specific time and location of the conference.
All personal travel costs and accommodations are the responsibility of
the attendees.


Upon receipt, applications will be reviewed by AHCPR staff for
completeness and responsiveness.  Incomplete applications will be
returned to the applicant without further consideration.  If the
application is not responsive to the RFA, AHCPR staff will contact the
applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next review cycle for grant applications.

All responsive applications will undergo peer review for scientific
merit by an AHCPR chartered review committee of non-Federal experts.
Applications that are recommended for further consideration and that
request total direct costs in excess of $250,000 will subsequently be
reviewed by the National Advisory Council for Health Care Policy,
Research, and Evaluation.

Peer review will take into account the following review criteria:

o  significance and originality of the goals of the project from a
scientific or technical standpoint;

o  adequacy of the methodology proposed to carry out the project;

o  availability of data or the proposed plan to collect data required
in the analysis;

o  adequacy and appropriateness of the plan for organizing and carrying
out the project;

o  qualifications of the Principal Investigator and proposed staff;

o  reasonableness of the proposed budget in relation to the project;

o  adequacy of the facilities and resources available to the applicant;

o  adequacy of the proposed means for protecting against or minimizing
adverse effects of project-related activities upon humans, animals, or
the environment.


The following will be considered in making funding decisions:

o  recommendations of the peer review committee and the National
Advisory Council;

o  assurance provided in the research application and the fiscal plan
that effective use will made of grant funds;

o  business management capability of the applicant;

o  competence and skill of the staff, especially the senior personnel,
in light of the scope of the project;

o  probable utility of findings for dealing with concerns of this RFA
and MEDTEP; and

o  relative priority of the proposed project in light of other
established priorities.


Written and telephone inquiries concerning this RFA are encouraged. The
opportunity to clarify any issues or to address questions from
potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Lynn Bosco, M.D., M.P.H.
Center for Medical Effectiveness Research
Agency for Health Care Policy and Research
2101 East Jefferson Street, Suite 605
Rockville, MD  20852
Telephone:  (301) 227-8485


Eleanor M. Perfetto, Ph.D., R.Ph.
Center for Medical Effectiveness Research
Agency for Health Care Policy and Research
2101 East Jefferson Street, Suite 605
Rockville, MD  20852
Telephone:  (301) 227-8485

Direct inquiries regarding administrative and budgetary matters to:

Ralph L. Sloat
Chief, Grants Management Branch
Office of Planning and Resource Management
Agency for Health Care Policy and Research
2101 East Jefferson Street, Suite 601
Rockville, MD  20852
Telephone:  (301) 227-8447


This program is described in the Catalog of Federal Domestic Assistance
No. 93.180.  Awards are made under authority of Title IX of the Public
Health Service Act (42 U.S.C. 299-299c-6) and section 1142 of the
Social Security Act (42 U.S.C. 1320b-12); and administered in
accordance with PHS grants policies, program regulations (42 CFR, Part
67, Subpart A), and other applicable Department regulations.  The
requirements of Executive Order 12372, "Intergovernmental Review of
Federal Programs," are not applicable to AHCPR research grant programs.

Selected References

Agency for Health Care Policy and Research. (1990, March). Program
Note: Medical Treatment Effectiveness Research. (Publication No.
OM90-0059) Rockville, MD: Public Health Service.

Agency for Health Care Policy and Research. (1990, September). AHCPR
Purposes and Programs. (Publication No. OM90-0096) Rockville, MD:
Public Health Service.

Agency for Health Care Policy and Research. (1991, April). Report to
Congress: The Feasibility of Linking Research-Related Data Bases to
Federal and Non-Federal Medical Administrative Data Bases. (Publication
No. 91-0003) Rockville, MD: Public Health Service.

American Academy of Orthopedic Surgeons, Subcommittee on Outcomes
Studies. (1991, January). Fundamentals of Outcomes Research. Park
Ridge, IL: American Academy of Orthopedic Surgeons.

Avorn, J.L. and S.B. Soumerai. (1983). Improving Drug Therapy Decisions
Through Educational Outreach: A Randomized Controlled Trial for
Academically Based "Detailing." New England Journal of Medicine 308,
pp. 1457-63.

Bloom B.S. and J. Jacobs. (1985, July). Cost Effects of Restricting
Cost-Effective Therapy. Medical Care 23, pp. 872-80.

Echt D.S., P.R. Liebson, L.B. Mitchell, et al.  (1991, March 21)
Mortality and Morbidity in Patients Receiving Encainide, Flecainide or
Placebo. The Cardiac Arrhythmia Suppression Trial.  New England Journal
of Medicine 324(12), pp.781-8.

FDC Reports, Inc. (1991, December 16). FDA to Stress Rx Patient
Information With Publicity Effort in Upcoming Months. FDC Reports ("The
Pink Sheet"), p. 7.

Hepler C.D. and L.M. Strand. (1990, March). Opportunities and
Responsibilities in Pharmaceutical Care. American Journal of Hospital
Pharmacy 47, pp. 533-43.

Hillman, A.L., J.M. Eisenberg, M. V. Pauly, et al. (1991, May 9).
Avoiding Bias in the Conduct and Reporting of Cost-Effectiveness
Research Sponsored by Pharmaceutical Companies. New England Journal of
Medicine 324 (19), pp. 1362-1365.

Lipton, H.L. and J.A. Bird. (1991, December). Drug Utilization Review:
State-of-the-Science and Directions for Outcomes Research. Unpublished
manuscript prepared for AHCPR.

Payne, S.M.C. (1987, December). Identifying and Managing Inappropriate
Hospital Utilization: A Policy Synthesis. Health Services Research
22:5, pp. 709-769.

Raskin, I.E. and C.W. Maklan. (1991, June). Medical Treatment
Effectiveness Research:  A View From Inside the Agency for Health Care
Policy and Research. Evaluation and the Health Professions, pp.

Ray, W.A. and M.R. Griffin. (1991, November). Pharmaceutical
Effectiveness Research: Meeting Information Needs of Clinical and
Policy Decision Making. Unpublished manuscript prepared for AHCPR.

Reeder, C.E., W.M. Dickson, C.M. Kozma, et al. (1991, October). Patient
Factors Influencing the Utilization of Pharmaceuticals and
Pharmaceutical Care. Unpublished manuscript prepared for AHCPR.

Schaffner, W., W.A. Ray, C.F. Federspiel, and W.O. Miller. (1983).
Improving Antibiotic Prescribing in Office Practice: A Controlled Trial
of Three Educational Methods. Journal of the American Medical
Association 250, pp.1728-32.

Soumerai, S.B., D. Ross-Degnan, J. Avorn, et al. (1991, October 10).
Effects of Medicaid Drug-Payment Limits on Admission to Hospital and
Nursing Homes. New England Journal of Medicine 325(15), pp. 1072-1077.

Strand, L.M. and P.C. Morley. (1991, November).  Pharmacists' Cognitive
Services. Unpublished manuscript prepared for AHCPR.

Stergachis A., J.S. Gardner, and T.D. Koepsell. (1991, November).
Methodological Issues in Pharmaceutical Outcomes Research. Unpublished
manuscript prepared for AHCPR.


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