Full Text HS-94-002

MEDICAL TREATMENT EFFECTIVENESS RESEARCH -- PORT-IIs

NIH GUIDE, Volume 22, Number 25, July 16, 1993

RFA:  HS-94-002

P.T. 34

Keywords: 
  Disease Prevention+ 
  Health Promotion 
  Treatment, Medical+ 
  Health Services Delivery 
  Health Care Economics 


Agency for Health Care Policy and Research

Letter of Intent Receipt Date:  October 1, 1993
Application Receipt Date:  November 16, 1993

PURPOSE

This announcement solicits applications to conduct innovative and
timely research that will provide convincing evidence for or against
the effectiveness and cost effectiveness of alternative clinical
interventions for the prevention, diagnosis, treatment, and
management of common clinical conditions.  The Agency for Health Care
Policy and Research (AHCPR) developed this solicitation as part of
the Medical Treatment Effectiveness Program (MEDTEP).  These awards
will constitute a new generation of MEDTEP research and an extension
of work carried out by AHCPR's Patient Outcomes Research Teams
(PORTs).  The new projects, called PORT-IIs, will have potential to
make substantial contributions to the improvement of health outcomes.
Their results will be relevant to patients, health care providers,
and policymakers.

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.  The AHCPR
urges applicants to submit grant applications with relevance to the
specific objectives of this initiative.  Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report: Stock No.
017-001-00474-0 or Summary Report:  Stock No. 017-001-004374-1)
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

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.  Applications from minority and women
investigators are encouraged.

MECHANISM OF SUPPORT

This RFA will use the research project grant (R01) mechanism.
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.  The total requested project period for
applications submitted in response to this RFA may not exceed five
years.  While the grants under this solicitation may vary in cost,
most individual projects are expected to request less than $1 million
total direct costs per year.  The earliest possible award date will
be July 1, 1994.  Annual progress reviews by AHCPR and the
availability of funds will determine the continuation of grants up to
the five year limit.

FUNDS AVAILABLE

The AHCPR expects to award up to $7 million in Fiscal Year 1994 to
support the first year of 5 to 10 studies.  The number of awards will
be contingent on the availability of funds and the quality of the
applications.

RESEARCH OBJECTIVES

Background and Conceptual Framework

Since 1989, AHCPR has made a major investment and major advances in
medical effectiveness/patient outcomes research, especially through
the set of special, multi-faceted projects known as Patient Outcomes
Research Teams (PORTs).  This RFA announces the second generation of
special projects, PORT-IIs, a pragmatic program that continues to put
the patient foremost and to emphasize the policy significance of
understanding what health care is most effective.  What is new in
PORT-IIs is the effort to expand the potential for discovery by
encouraging individual customization and creativity in research
designs.  The individual methods common in PORTs (e.g., meta-analysis
and variations studies based on analysis of administrative data) are
available for, but not required in, PORT-IIs.

PORT-IIs will focus on the establishment of direct linkages between
practice and outcomes and on research methods that facilitate direct
comparisons of alternative clinical strategies.  They are expected to
start with carefully formulated research questions and employ
research strategies tailored to the selected condition and the
population at risk.  Emphasis is placed on research designs that can
answer convincingly and efficiently questions about which clinical
strategies lead to the desired outcomes.

Research under AHCPR's Medical Treatment Effectiveness Program is
concerned with enhancing the "effectiveness," "cost effectiveness,"
and "appropriateness," of health care, as defined below.

"Effectiveness," as distinct from "efficacy," refers to the outcomes
experienced by or observed in patients in routine clinical practice.
Effectiveness studies take into account the complexities that result
from the many clinical and non-clinical variables that influence
practice and outcomes.  At a minimum, these include relevant
comorbidities, medical history, and adherence to treatment
recommendations; relevant demographic, socioeconomic, and cultural
characteristics; and patients' values and preferences.  They may
include differences in clinicians' training, skills, and practice
styles.  Differences in organizational factors, such as financial
incentives and composition of the clinical team, also may be
considered as important independent variables.  It is expected that
the result of this inclusionary approach will be a set of studies the
findings of which can be generalized to health care as it is
typically received and practiced in the community.

The PORT-II's emphasis on the generalizability of findings excludes
from consideration, under this RFA, typical "efficacy" studies.  A
traditional randomized controlled trial, the findings of which relate
only to the potential benefits of clinical interventions under ideal
circumstances and in patients who meet narrow eligibility criteria
would be non-responsive to this RFA.  However, the RFA does include
clinical trials that are designed to answer effectiveness questions,
i.e., questions about outcomes in persons who are representative of
those with the condition that is being studied.  Such studies are
referred to as "effectiveness trials."

"Cost-effectiveness" analyses most often compare the direct monetary
costs of health care plus the associated indirect costs (e.g., lost
work) with the benefits and burdens of the intervention.
Applications responsive to this RFA should address questions of cost
effectiveness if or when the interventions to be compared are
associated with significant differences in cost or significant
differences in effect.

The MEDTEP concept of "appropriateness" encompasses both clinical and
non-clinical dimensions.  It includes consideration not only of the
fit between the intervention and the objective and technical aspects
of the patient's condition, but also consideration as to whether the
known risks and costs of the intervention, and the predicted
outcomes, are acceptable to individual patients and to the public.

In assessing effectiveness, cost effectiveness, and appropriateness,
investigators are encouraged to measure outcomes that emphasize the
patient's perspective and to consider how patient preferences
influence evaluations of the outcomes.  In general, outcomes are to
include survival, symptom relief, patient-reported quality of life,
functional status, satisfaction with care, and costs.  Analysis of a
broad set of outcomes is desirable, but it is essential that the
research address the most significant outcomes for the particular
condition under study, whether these are long - or short-term.

SPECIAL REQUIREMENTS

Topic Selection

This RFA accommodates an extremely wide range of clinical subjects.
Public interest in health care reform and more cost-effective use of
health care resources makes it important that AHCPR focus on
questions with significant potential to improve outcomes and/or
decrease costs.  The AHCPR's authorizing legislation places special
emphasis on conditions that are common and costly in the Medicare
program.  Applicants are expected to present a strong case for their
selected topic in a critical literature review.  The review should
address the clinical and policy significance of the condition,
provide evidence of controversy or information gaps regarding current
clinical strategies, and support the formulation of the proposed
research question(s).  The formulation of the problem should reflect
understanding of the issues regarding clinical decisionmaking and the
translation of study findings into clinical practice.  Further, the
discussion should satisfy reviewers that the important questions
about outcomes can be answered within the proposed grant period.

Most PORT-II studies will be condition-specific or
technology-specific.  Condition-specific studies should focus on an
important clinical condition and the most important interventions for
its prevention, diagnosis, treatment, and/or management.  In addition
to clinical problems that are significant in the Medicare population,
this announcement includes conditions and technologies that are
common and costly in children, adolescents, and adults under age 65.
This includes well-defined diseases (e.g., breast cancer, pediatric
asthma), as well as symptoms and conditions (e.g., headache, fatigue,
obesity).  While acute or chronic conditions may be selected, the
AHCPR is especially interested in studies of chronic problems and
those treated in ambulatory settings.  To be responsive to this RFA,
the selected condition must meet all of the following MEDTEP
criteria:

o  high incidence or prevalence in the general population or in major
population subgroups;

o  controversy or open questions over the effectiveness and relative
effectiveness of available clinical strategies; and

o  high cost, whether due to the number of people needing care, high
cost of care, or high indirect cost.

This announcement encompasses studies that compare two or more
distinctly different clinical approaches to the prevention,
diagnosis, treatment, management, or rehabilitation of common
clinical conditions.  Examples of responsive studies include
comparisons of:  medical vs. surgical treatment, radical vs.
conservative surgery, psychotherapy vs. pharmacotherapy, or invasive
vs. non-invasive screening tests.  Other possible comparisons could
include care prescribed or provided by different kinds of health care
professionals (e.g., physicians, nurses, therapists) and care
provided in different settings.

If it is not feasible to address all important treatment options in a
single study, applicants must identify the specific interventions the
study will address and provide justification for these selections.
In general, studies that can carry out the most comprehensive
assessments of the pertinent clinical strategies will be of greater
interest to AHCPR.

Methods

Investigators are encouraged to design new research strategies, to
use new combinations of methods, or to tailor existing methods to
their research question(s) so that convincing evidence will be
obtained for, or against, the effectiveness of alternative clinical
interventions.

Research methods that can be employed include, but are not limited
to, quasi-experimental designs, case-control studies, cohort studies,
effectiveness trials, meta-analyses, cost-effectiveness analyses,
decision modeling, and combinations of these methods.  Sources of
data about patient outcomes can include:  new, established, or
adapted surveys of patients and providers; clinical registries; and
clinical records from practice-based networks, health maintenance
organizations, and other health care providers.  In many cases,
primary data, collected prospectively, may be most appropriate to the
questions and methods involved.  However, when secondary data will
provide adequate information and an efficient means to address the
research questions, applicants are encouraged to use such data.  For
example, administrative data, although they generally lack clinical
detail, may be useful in identifying cases and controls, estimating
costs, or measuring selected outcomes.

The application should be explicit in its strategy for case-finding
and its justification that the results will be generalizable to
patients cared for in routine clinical practice.  The application
should also define the strategy for making direct comparisons of
alternative treatments.

The application should be explicit and detailed in describing the
data collection and analysis.  In all cases, the methods and data
employed must be justified in terms of their potential for answering
the effectiveness research questions under study.  There should be
evidence of adequate attention to relevant characteristics of each of
the following:

o  the patients and persons at risk for the condition, especially
characteristics that may affect case-finding, case-definition, and
generalizability;

o  the condition, especially characteristics that affect quality of
data and complexity of analysis (e.g., diagnosis is definite vs.
equivocal, course is steady vs. sporadic);

o  the clinical interventions (duration and timing, stability of
technology);

o  the outcomes (e.g., measurability, timing, stability);

o  the providers (e.g., training, financial incentives, liability
concerns, accessibility);

o  available data and measures; and

o  the social and cultural context of illness and health care,
especially characteristics that affect disease prevalence, health
behavior, access to care, and conduct of research.

Project Organization

To adequately address the clinical and non-clinical dimensions of
effectiveness questions, most studies will require multidisciplinary
research teams.  In all cases, the composition of the team and
relative time commitments of each member should be well justified in
terms of substantive knowledge, methodological expertise, and
experience in conducting or managing related research projects.  It
is further expected that the team include at least one individual who
is actively involved in the type(s) of patient care central to the
study and who contributes understanding of how and why clinical
decisions are made in routine clinical practice.

Applicants are encouraged to take full advantage of opportunities for
efficient enhancements of available expertise, data, and other
research resources.  This might include collaboration with
researchers and practitioners outside their own institutions,
creative use of existing data, or "piggybacking" on other data
collection activities.  Another possibility for leveraging research
resources is to conduct comparisons of outcomes where existing
practice patterns are known to differ (e.g., across care settings,
health care systems, or international borders).

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS CONCERNING INCLUSION OF WOMEN AND
MINORITIES IN RESEARCH STUDY POPULATIONS

The AHCPR requires all applicants for research grants to include
minorities and women in study populations so that research findings
can be of benefit to all persons at risk of the disease, disorder, or
condition under study.  Special emphasis must be placed on including
minorities and women in studies of diseases, disorders, and
conditions which disproportionately affect them.  This policy applies
to males and females of all ages.  If women or minorities are
excluded or inadequately represented in research, a clear and
compelling rationale must be provided.

This policy applies to all AHCPR research grants.  The AHCPR will not
award grants for applications which do not comply. If the application
does not contain the required information, it will be returned
without review.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues should be addressed in developing a research
design and sample size appropriate for the scientific objectives of
the study.  This information should be included in the form PHS 398
in Sections 1 to 4 of the Research Plan and summarized in Section 5,
Human Subjects (or in the program narrative section of form PHS 5161
for State and local governments).

Applicants are urged to assess carefully the feasibility of including
the broadest possible representation of minority groups.  However,
AHCPR recognizes that it may not be feasible or appropriate in all
research projects to include representation of the full array of
United States racial/ethnic minority populations (i.e., American
Indians/Alaskan Natives, Asian/Pacific Islanders, Blacks, Hispanics).
Where appropriate, the applicant must provide the rationale for
studies on single minority population groups.

For foreign awards, the policy on inclusion of women applies fully.
Since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.

Peer reviewers will address specifically whether the applicant's
research plan conforms to these policies.  If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed and the justification for the
selected study population is inadequate, it will be considered a
scientific weakness or deficiency in the study design and will be
reflected in the priority score assigned to the application.

LETTER OF INTENT

Prospective applicants are asked to submit by October 1, 1993, a
letter of intent that includes a descriptive title of the proposed
research; the names, addresses (including institutions), and
telephone numbers of the Principal Investigator and other key
personnel; and the number and title of this RFA.  Although a letter
of intent is not required, is not binding, and does not enter into
the review of subsequent applications, the information that it
contains allows AHCPR staff to estimate the potential review workload
and to avoid possible conflict of interest in the review.

The letter of intent is to be sent to Dr. Richard Greene at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be
used.  (State and local government agencies may use form PHS 5161 and
follow those requirements for copy submission.)  These forms are
available at most institutional offices of sponsored research; the
Office of Grant Information, Division of Research Grants, National
Institutes of Health, Westwood Building, Room 449, Bethesda, MD
20892, telephone 301-435-0714; and the Scientific Review Branch,
Agency for Health Care Policy and Research, 2101 East Jefferson
Street, Suite 602, Rockville, MD 20852, telephone 301-227-8449 (after
July 31, telephone 301-594- 1449).

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, signed, original application and four legible copies
of form PHS 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 by the Division of Research
Grants by November 16, 1993.  If an application is received after
that date, it will be returned to the applicant.

One copy, labeled "Advance Copy," must 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

Failure to provide this advance copy will result in the return of the
application to the applicant.

REVIEW CONSIDERATIONS

Applications will be reviewed initially by the Division of Research
Grants, NIH, for completeness and by AHCPR program staff for
responsiveness to the RFA.  Incomplete and unresponsive applications
will be returned to applicants without further consideration.  Review
criteria for AHCPR grant applications are significance and
originality from a scientific and technical viewpoint; adequacy of
the method; availability of data or proposed plan to collect data
required for the project; qualifications and experience of the
principal investigator and proposed staff; adequacy of the plan for
organizing and carrying out the project; reasonableness of the
proposed budget; and adequacy of the facilities and resources
available to the applicant.

Applications will be evaluated in accordance with the criteria stated
above for scientific/technical merit and the special review criteria
listed below by an appropriate peer review group.  Applications
requesting total direct costs in excess of $50,000 may be reviewed by
AHCPR's National Advisory Council for Health Care Policy, Research,
and Evaluation.

Special Review Criteria

The major scientific criterion for evaluating applications under this
solicitation is the potential for obtaining convincing, new evidence
for, or against, the effectiveness of alternative interventions that
are significant in preventing, diagnosing, treating, or managing the
selected condition.  The selected condition must meet the MEDTEP
criteria listed above under Topic Selection.  Separate consideration
is given to the significance of the research question(s).

The review committee will independently evaluate each application
received in response to this RFA against the following special
scientific and technical review criteria:

o  scientific importance of the clinical topic and particular
clinical interventions to be studied, as justified in a review of the
literature;

o  evidence that the proposed research plan can answer the research
question(s) within the project period, i.e., that the science base is
adequate, data are available or can be obtained, length of follow-up
is sufficient;

o  attention to technical issues in case-definition, case-finding,
data collection, and analysis;

o  quality and adequacy of the proposed data;

o  justification for focus on specified outcomes;

o  adequacy of outcome measures, including measurement of costs if
applicable;

o  extent to which research design permits direct comparisons of
treatment effectiveness and of cost effectiveness;

o  evidence of understanding of the issues in clinical decisionmaking
and the translation of research findings into clinical practice;

o  sensitivity to patient heterogeneity and individual preferences;

o  generalizability of results;

o  specification of useful findings or products and identification of
constituency(ies) for these;

o  cost effectiveness of research plan;

o  composition of the research team, including evidence of necessary
experience and expertise, and appropriateness of relative time
commitments; and

o  evidence of productive collaborations (e.g., with other
institutions, appropriate professional groups, other sources of
support).

AWARD CRITERIA

Applications will compete for available funds with all other
applications for this RFA.  The following will be considered in
making funding decisions:  quality of the proposed project as
determined by peer review and availability of funds.  The earliest
anticipated date of award for applications will be July 1, 1994.

INQUIRIES

Written and telephone requests for the RFA and the opportunity to
clarify any issues or questions from potential applicants are
welcome.

Inquiries regarding programmatic issues and the letter of intent may
be addressed to:

Richard Greene, M.D., Ph.D.
Director, Center for Medical Effectiveness Research
Agency for Health Care Policy and Research
2101 East Jefferson Street
Rockville, MD  20852
Telephone:  (301) 227-8485 (through July 31, 1993) or (301) 594-1485
(effective August 1, 1993)

Direct inquiries regarding fiscal matters to:

Ralph L. Sloat, Grants Management Officer
Agency for Health Care Policy and Research
2101 East Jefferson Street
Rockville, MD  20852
Telephone:  (301) 227-8447 (through July 31, 1993) or (301) 594-1447
(effective August 1, 1993)

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance, No. 93.180.  Awards are made under authorization of the
Public Health Service Act, Title IX, as amended by Public Laws
101-239 and 102-410, (42 U.S.C. 299-299c-6) and Section 1142 of the
Social Security Act (42 U.S.C. 1320b- 12).  Awards are administered
under the PHS Grants Policy Statement; and Federal Regulations 42 CFR
Part 67, Subpart A, and 45 CFR Part 74 (45 CFR Part 92 for State and
local governments).  This program is not subject to the
intergovernmental review requirements of Executive Order 12372.

.

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