Subject: NIH GUIDE - RFA HL-91-08-P - V20(33) 09/06/91
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Mon, 09 Sep 91 10:41 EST

Hi Paul,
This is #10 of 11 of the RFAs for 910906.  Please post
this one to the Listserver as:
RFAHL-91-08-P.910906.
     Thanks, M. G. Broaddus
 ---------------------------- Text of forwarded message -----------------------
 
$$XID RFA HL9108P HL-91-08-P P1O1 **************************************
 
REQUEST FOR APPLICATIONS
 
RFA:  HL-91-08-P
 
EVALUATION OF ADHERENCE INTERVENTIONS IN CLINICAL TRIALS
 
P.T. 34; K.W. 0755015, 0715040, 0715165, 0715032
 
National Heart, Lung, and Blood Institute
National Center for Nursing Research
 
Letter of Intent Receipt Date:  October 1, 1991
Application Receipt Date:  November 19, 1991
 
PURPOSE
 
The Division of Epidemiology and Clinical Applications (DECA) of the
National Heart, Lung, and Blood Institute (NHLBI) and the National
Center for Nursing Research (NCNR) invite applications for a cooperative
agreement to evaluate the effectiveness of intervention strategies
designed to enhance patient adherence in clinical trials.  Studies
responsive to this Request for Applications (RFA) will involve the use
of clinical trials of pharmacologic therapies in the areas of
cardiovascular, lung, and blood diseases.
 
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 RFA,
Evaluation of Adherence Interventions in Clinical Trials, is related to
the priority area of heart disease and stroke.  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).
 
DISCIPLINES AND EXPERTISE
 
Applicants must have knowledge of the major theoretical approaches
underlying adherence interventions, as well as expertise in the design
and evaluation of adherence-enhancing interventions.  In addition,
knowledge of clinical trial design and methodology is essential.
 
Applicants must demonstrate the capability for establishing a working
relationship with clinical center staff for the particular trial used,
including access to the patient population eligible for the trial.
 
ELIGIBILITY
 
Applications may be submitted by for-profit or nonprofit organizations,
whether public or private, such as universities, colleges, hospitals,
laboratories, units of State or local governments, and eligible agencies
of the Federal Government.  Applications from minority individuals and
women are encouraged.  Applications from foreign institutions will be
considered only if the applicant provides detailed evidence of special
relevant opportunities not available in a U.S. population.
 
BACKGROUND
 
The success of any therapeutic intervention, whether preventive or
curative, is ultimately dependent on the individual's adherence to
treatment.  Unfortunately, the failure of a large percentage of patients
to adhere to prescribed medical regimens is a widely recognized and
well-documented phenomenon.  Sackett and Haynes (1976) estimate that as
many as 50 percent of patients do not take their prescribed medications,
and of those remaining, less than two-thirds take their medication as
prescribed.
 
Non-adherence to treatment regimens is a special problem in clinical
trials.  Participants in a clinical trial can fail to adhere to the
study protocol for a variety of reasons, including forgetting to take
the medication, modifying medication regimens because of treatment side
effects, and failing to return to the clinic for follow-up visits.
Although adherence in clinical trials has been reported as better than
that in the general population, with estimates of 80 percent and above,
there is evidence that these rates overestimate actual adherence due to
the use of adherence measures that are easily manipulated by patients,
such as self-report and pill counts.  More reliable data, obtained using
electronic medication usage monitors, that unobtrusively record drug
usage, have documented the widespread phenomena of "pill dumping" and
increased usage of medication just prior to clinic visits.  Even
biochemical measures would not reflect actual adherence rates if
patients increase drug dosage before a visit.  Thus, a reliance on 80
percent adherence rates in clinical trials may be misleading.
 
Lack of adherence to the intervention in a clinical trial can have a
major impact on the costs and validity, both internal and external, of
the study.  Poor adherence affects the sensitivity of the study to
detect treatment effects, thus requiring increased sample sizes and
consequently increased costs.  Non-adherence can also result in an
underestimation of drug effects, with a resultant overestimation of
dosing requirements for optimal efficacy (Joyce, 1962; Urquhart and
Chevalley, 1988).  Differential patient attrition across conditions can
interfere with the unambiguous interpretation of study results, since
there may be no way to determine the effects of therapy independent of
adherence (Bhaskar, Reitman, Sacks et al., 1986).  In addition, the
generalizability of a study is affected by high attrition rates, since
the study's results may apply only to those patients who comply with
treatment regimens or do not experience side effects.
 
As discussed in the 1987 NHLBI-sponsored Working Conference on the
Adoption and Maintenance of Behaviors for Optimal Health, a number of
studies have attempted to define the reasons for poor patient adherence
and to delineate successful intervention strategies for enhancing
adherence.  The results of these studies suggest little relationship
between poor adherence and characteristics such as age, gender, marital
status, education, and economic status.  There is some evidence,
however, that adherence is enhanced with the use of less complex medical
regimens, shorter treatment periods, and therapies with few side effects
(Dunbar, 1990).
 
Various characteristics of the individual patient, the treatment
situation, and the interaction between patient and physician have been
studied with respect to patient adherence.  These include the patient's
belief in the seriousness of the illness, the patient-doctor
relationship, patient and physician expectations, the influence of the
work setting, degree and type of support from family members, and
characteristics of the health delivery system.  Examples of
interventions tested include the use of explicit instructions tailored
to the specific patient, the provision of detailed feedback to patients,
and increased opportunities for the patient to ask questions of the
provider.  A large number of studies have focused on methods of
monitoring patient compliance.  An example is the use of patient
tracking systems that involve reminders to patients regarding
appointments and medication refills.  A more recent phenomenon is the
use of sophisticated microelectronic technologies that monitor patient
adherence via automatic recording of medication usage.
 
Although there is a large body of data regarding the factors that
influence adherence, often studies are conducted on small samples, using
non-patient populations.  There has been little attempt to compare
several types of interventions or to focus on the comparative
cost-effectiveness of adherence-enhancement strategies.  Even less
information is available on the effects of various adherence
interventions within clinical trials.  The best known example of an
attempt to document the success of interventions aimed at increasing
adherence in a clinical trial context is the Lipid Research
Clinic-Coronary Primary Prevention Trial (LRC-CPPT) that included a
dropout recovery program involving detailed surveillance of patient
adherence, intensive counseling, and specific procedures designed to
recover patients who had ceased participating in the trial (Probstfield,
Russell, Henske, Reardon and Insull, 1986).  However, no studies have
been done in a clinical trial context that experimentally vary adherence
strategies in order to compare the effectiveness of several approaches
to increasing adherence.
 
In summary, little research has been done comparing the effectiveness
(including the cost effectiveness) of various strategies designed to
enhance adherence in clinical trials.  Such studies would allow clinical
trial researchers to make more effective use of adherence strategies,
thus increasing the efficiency of clinical trials and improving patient
outcomes.
 
SCIENTIFIC PLAN
 
Studies responsive to this solicitation must systematically compare the
effects of two or more intervention strategies on patient adherence
within an existing or planned clinical trial.  Because adherence
strategies will vary based on whether the trial involves drug versus
lifestyle intervention, clinical trials to be used will be limited to
those involving pharmacological therapies in the areas of
cardiovascular, lung, and blood diseases.  The proposed studies must:
 
o use experimental designs in which patients are randomly assigned to
one of several adherence intervention conditions to assess the
effectiveness of various strategies to increase adherence;
 
o use a clear definition of adherence as the dependent variable and
well-defined measures of adherence.  Whenever feasible, the studies
should make use of the most recent advances and/or innovations in
adherence measurement (e.g., computer monitoring systems);
 
o evaluate the cost effectiveness of the various strategies used;
 
o whenever possible, include a characterization of subgroups of patients
who are most affected by the different intervention strategies;
 
o take into account differential attrition rates across treatments in
evaluating the effects of different interventions.
 
Each of the interventions used must be grounded in an explicit
theoretical framework; examples of theoretical approaches underlying
commonly used intervention strategies include learning theory (e.g.,
behavior modification techniques, such as those used in contingency
contracting); cognitive theory (e.g., cognitive restructuring,
expectancy and problem-solving strategies); social learning theory
(e.g., modelling, self-efficacy approaches); and social network models
(e.g., family support, "buddy systems").  Furthermore, only those
strategies that have been previously shown to increase adherence in
non-clinical trial contexts and that are relatively easy to administer
(i.e., do not require extensive expertise or training) will be
considered.
 
Specific interventions include:  (1) relatively modest interventions
(e.g., mailed/phone reminders, self-recording of medications taken,
systematic feedback from the provider regarding adherence behaviors);
(2) more intensive interventions (e.g., specific, structured
communication patterns between the provider and patient; prompts or cues
for taking medications, such as marked pill boxes with date and time);
and (3) high-intensity interventions, such as therapeutic contracts
(written contracts with contingency reinforcement), social support
networks, including spouses and other family members; relapse prevention
programs; social problem-solving approaches; and self-management
packages.
 
Outcome measures must be well-defined and, whenever feasible, take
advantage of recent technological advances that allow for more reliable
estimates of adherence.
 
Applications must provide detailed information on the population to be
studied.  Detailed justifications for sample sizes will be required, as
will assurances that projected sample sizes can be obtained.  In
addition, since implementation of these studies will take place within
the context of planned or ongoing clinical trials, assurances must be
obtained from the clinical trial investigators regarding their
cooperation in the use of the trial for a study of adherence
interventions.
 
The maximum duration of the proposed research project will be three
years.  Variations in project length within this period and variations
of program phases may occur due to differences in the time needed for
recruitment, intervention, and follow-up.  The projected timetable is:
 
Phase 1:  Protocol refinement and standardization:  nine months to one
year
Phase 2:  Recruitment of subjects, intervention, and follow-up
activities, preliminary data analysis:  one to two years
Phase 3:  Data analysis and reporting:  six months
 
At the completion of the project, the Principal Investigators (PI) must
be prepared to provide a report with:  (a) detailed recommendations
regarding the adherence interventions found to be most effective,
including characterization of subgroups of patients for whom the
interventions were most effective and comparisons of the cost
effectiveness of different adherence interventions; (b) a complete
description of the underlying theoretical bases for the recommended
interventions, as well as detailed procedures for carrying out the
interventions; (c) training, certification, and quality control
procedures for ensuring effective implementation of the recommended
adherence interventions.
 
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS
 
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required 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 should be placed on the need for
inclusion of minorities and women in studies of diseases, disorders and
conditions which disproportionately affect them.  This policy is
intended to apply to males and females of all ages.  If women or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population-based studies, a clear
compelling rationale should be provided.
 
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 Section 2,
A-D of the Research Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility of
including the broadest possible representation of minority groups.
However, NIH 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., Native Americans
(including American Indians or Alaskan Natives), Asian/Pacific
Islanders, Blacks, Hispanics).  The rationale for studies on single
minority population groups should be provided.
 
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.
 
The usual NIH policies concerning research on human subjects also apply.
Basic research or clinical studies in which human tissues cannot be
identified or linked to individuals are excluded.  However, every effort
should be made to include human tissues from women and racial/ethnic
minorities when it is important to apply the results of the study
broadly, and this should be addressed by applicants.
 
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.
 
If the required information is not contained within the application, the
application will be returned.
 
Peer reviewers will address specifically whether the research plan in
the application 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
assigning the priority score to the application.
 
All applications for clinical research submitted to NIH are required to
address these policies.  NIH funding components will not award grants or
cooperative agreements that do not comply with these policies.
 
STUDY RESPONSIBILITIES AND GOVERNANCE
 
Steering Committee.  Although the studies funded through this RFA will
differ with respect to the particular intervention strategies, diseases,
treatments, and subject populations used, it is expected that certain
aspects of the studies will be shared (e.g., random assignment
protocols, assessment of demographic and other baseline information on
subjects, training and quality-control procedures, outcome measures).
To facilitate comparability of research protocols with respect to common
aspects of the studies, a Steering Committee will be formed with overall
responsibility for decision-making regarding these shared aspects.  The
Steering Committee will be comprised of the PI of each study and the
three NIH project scientists.  Each PI will have one vote.  In addition,
the NIH will have one vote.  During Phase 1 of the program, the Steering
Committee will meet two times to:  (1) develop and finalize the shared
portions of the studies, and (2) review and coordinate the specific
intervention strategies being used.  Subsequent Steering Committee
meetings, to be held yearly, will include more detailed discussion of
data management and analysis issues, publication concerns, and study
progress.  Steering Committee meetings will also be attended by one to
two key staff from each project.
 
TERMS AND CONDITIONS OF AWARDS
 
It is anticipated that four awards will be made under this RFA for a
total of approximately $2.7 million (including direct and indirect
costs) over a three-year period.  Funding is expected to begin on or
about July 1, 1992.  Applicants must include in the budget sufficient
funds to allow travel of the PI and one to two key personnel to
Bethesda, MD, for two meetings (two-day meetings) in the first year and
one meeting per year thereafter.  Currently there are no plans with
respect to reissuance of this RFA.
 
The administrative and funding mechanism to be used to undertake this
program will be the cooperative agreement (UO1), an assistance
mechanism.  Under the cooperative agreement, the NIH assists and is
involved substantially with recipients in conducting a study by
facilitating performance of the effort in a "partner" role.  Consistent
with this concept, the tasks and activities in carrying out the studies
will be shared among the awardees and the NIH project scientists.  Thus,
there will be substantial programmatic involvement of the designated
NHLBI and NCNR project scientists above and beyond the levels
characteristic for traditional program management of grants.  The need
for this involvement arises from the complexity introduced by the
diverse interventions and study populations to be used.  In an effort to
maximize the usefulness of information obtained from the set of funded
projects, the assistance of the NIH project scientists will center on
coordinating the:  (1) study designs and protocols; (2) interventions
being tested; and (3) outcomes being measured.
 
Specifically, the tasks or activities in which the awardees will have
substantial responsibilities include protocol development, participant
recruitment and follow-up, data collection, quality control, interim
data and safety monitoring, final data analysis and interpretation,
preparation of publications, and collaboration with other awardees and
the NIH project scientists.  The NIH project scientists will have
substantial responsibilities for protocol development, quality control,
interim data and safety monitoring, final data analysis and
interpretation, preparation of publications, collaboration with
awardees, and coordination and performance monitoring.  It is
anticipated that awardees will have lead responsibilities in protocol
development, interim data and safety monitoring, final data analysis and
interpretation, and in the preparation of most publications.  The NIH
project scientists will have lead role responsibilities in quality
control, may have lead responsibilities in preparation of some
publications, and will serve as members of the Steering Committee.
 
The awardees will proceed from Phase 1 to Phase 2 only with the
concurrence of the NIH.  In addition, the appointment of any new or
replacement key personnel is subject to the concurrence of the NIH.
 
Disagreements that may arise between award recipients and the NIH on
programmatic decisions on scientific-technical matters within the scope
of the award may be brought to arbitration.  An arbitration panel will
be composed of three members:  one selected by the Steering Committee
(with NIH members not voting) or by the individual awardee in the event
of an individual disagreement, a second member selected by the NIH and
the third member selected by the two prior members.  This special
arbitration procedure in no way affects the awardee's right to appeal an
adverse action that is otherwise appealable in accordance with the PHS
regulations at 42 CFR part 50, subpart D and HHS regulation at 45 CFR
part 16.
 
These special terms of award are in addition to and not in lieu of
otherwise applicable OMB administrative guidelines, HHS Grants
Administration Regulations at 45 CFR part 74, and other HHS, PHS, and
NIH grants administration policy statements.
 
The NIH reserves the right to terminate or curtail the study (or an
individual award) in the event of (a) substantial shortfall in
participant recruitment, data reporting, quality control, or other major
breech of the protocol; or (b) substantive deviations from the RFA
objectives or agreed-upon protocol; or (c) human subject ethical issues
that may dictate a premature termination.
 
REVIEW PROCEDURES AND CRITERIA
 
All applications will be judged on the basis of the scientific merit of
the proposed study and the documented ability of the applicants to
conduct the essential study components as outlined under the Scientific
Plan section of this RFA.
 
Review Method.  Applications must be submitted to the NIH Division of
Research Grants and will be dually assigned to NHLBI and NCNR.  Upon
receipt, applications will be reviewed for responsiveness to the
objectives of this RFA.  If an application is judged unresponsive, the
applicant will be contacted and given an opportunity to withdraw the
application or to have it considered for the investigator-initiated
grant program of the NIH.  If the application submitted in response to
this RFA is substantially similar to a research grant application
already submitted to the NIH for review, but has not yet been reviewed,
the applicant will be asked to withdraw either the pending application
or the new one.  Simultaneous submission of identical applications will
not be allowed, nor will essentially identical applications be reviewed
by different review committees.  Therefore, an application cannot be
submitted in response to this RFA that is essentially identical to one
that has already been reviewed.  This does not preclude the submission
of substantial revisions of applications already reviewed, but such
applications must include an introduction addressing the previous
critique.
 
Applications judged to be responsive by NHLBI/NCNR staff will be
reviewed for scientific and technical merit by an initial review group
that will be convened by the Division of Extramural Affairs, NHLBI,
solely to review these applications.  This initial review will include a
preliminary evaluation to determine scientific merit relative to the
other applications received in response to this RFA (triage).  The NIH
will remove from further consideration applications judged to be
noncompetitive and promptly notify the PI and the official signing for
the applicant organization.  Those applications judged to be competitive
will be further evaluated for scientific/technical merit by the usual
peer review procedures, including, if deemed appropriate, a reverse site
visit at the applicant's expense.  Subsequent review will be by the
NHLBI and NCNR Advisory Councils.
 
Review Criteria.  Applicants are encouraged to submit and describe their
own ideas on how best to meet the goals of the study.  Applications will
be judged primarily on the:  (1) overall scientific quality; (2)
qualifications and experience of the investigators in the design and
implementation of adherence interventions, and in the use of
experimental (preferably clinical trial) methodologies; (3) capability
to perform the work, including the availability of an appropriate
clinical trial within which to conduct a study of adherence
interventions and written assurances of cooperation from the PIs in the
clinical trial, including access to all relevant data being collected
for the clinical trial that is pertinent to the objectives of the
adherence interventions study; (4) availability of suitable numbers of
participants to ensure the ability to test study hypotheses; (5) ability
of key personnel to devote the time required to carry out the project;
(6) adequacy of facilities and supporting environment; and (7)
appropriateness of the budget for the work proposed.  In addition, a
willingness to collaborate with other study sites and NIH program staff
will be assessed.
 
Each application must include an adequately justified budget for each
phase of the study for the entire anticipated project period of three
years.  Estimates of personnel needs, including the PI, other
investigators, and support staff, must be included.
 
METHOD OF APPLYING
 
Letter of Intent.  Prospective applicants are asked to submit a letter
of intent that includes a descriptive title, names of the Principal and
Co-Investigators, and identify cooperating institutions.  The NIH
requests such letters only for the purpose of providing an indication of
the number and scope of applications to be received and usually does not
acknowledge their receipt.  A letter of intent is not binding, and it
will not enter into the review of any application subsequently
submitted, nor is it a necessary requirement for applications.  This
letter of intent to be received no later than October 1, 1991, is to be
sent to:
 
C. James Scheirer, Ph.D.
Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 548
5333 Westbard Avenue
Bethesda, MD  20892
 
Format for Applications.  Submit applications on form PHS 398 (revised
10/88), the application form for the traditional research project grant.
This form is available in an applicant institution's office of sponsored
research or business office and from the Office of Grants Inquiries,
National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda,
MD 20892 (telephone number (301) 496-7441).  Use the conventional format
for research project grant applications and ensure that the points
identified in the section on "Review Procedures and Criteria" are
fulfilled.
 
The format and instructions for budget estimates must be followed.
Indirect costs will be awarded in the same manner as for research
grants.  Budgets will be reviewed on the basis of appropriateness for
the work proposed.  Allowable costs and policies governing the research
grant programs of the NIH will prevail.  Overlapping support or
duplication of funding will not be allowed, and a summary of all actual
and pending sources of support for each key investigator participating
in the study must be included.  These summaries of other funding must
identify by name the PI of each award and include the source of the
funds with identifying grant or other award number, percent effort
committed, the amount of the award for the current year, the total
amount of the award, and the project period for which the award was
made.
 
This RFA is a one-time solicitation.  To identify the application as a
response to this RFA, check "yes" on Item 2 of Page 1 of the application
and enter the title, Evaluation of Adherence Interventions in Clinical
Trials, HL-91-08-P.
 
THE RFA LABEL INCLUDED IN THE 10/88 REVISION OF FORM PHS 398 MUST BE
AFFIXED TO THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL COMPLETED
APPLICATION FORM.  FAILURE TO USE THIS LABEL COULD RESULT IN DELAYED
PROCESSING AND REVIEW OF THE APPLICATION.
 
Application Procedure.  Send or deliver the completed application and
four signed, exact photocopies to:
 
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**
 
Send two additional copies of the application to:
 
C. James Scheirer, Ph.D.
Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 548
5333 Westbard Avenue
Bethesda, MD  20892
Telephone:  (301) 496-8818
 
IT IS IMPORTANT TO SEND THESE TWO COPIES AT THE SAME TIME AS THE
ORIGINAL AND FOUR COPIES ARE SENT TO THE DIVISION OF RESEARCH GRANTS.
OTHERWISE, THE NHLBI CANNOT GUARANTEE THAT THE APPLICATION WILL BE
REVIEWED IN COMPETITION FOR THIS RFA.
 
Applications must be received by November 19, 1991.  An application not
received by this date will be returned.
 
Timetable
 
Letter of Intent (optional)                 October 1, 1991
 
Application Receipt Date                    November 19, 1991
 
Technical/Scientific Review                 February 1992
 
Review by NHLBI and NCNR Advisory
      Councils                  May 14-15, 1992 and June 4-5, 1992
 
Anticipated Award Date                      July 1, 1992
 
Inquiries
 
Inquiries regarding this announcement may be directed to the following
Program Administrators:
 
Susan M. Czajkowski, Ph.D.
BMB/DECA
National Heart, Lung, and Blood Institute
Federal Building, Room 216
7550 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-9380
 
Sharlene M. Weiss, Ph.D., R.N.
National Center for Nursing Research
Building 31, Room 5B03
9000 Rockville Pike
Bethesda, MD  20892
Telephone:  (301) 496-0523
 
Eleanor Schron, M.S., R.N.
CTB/DECA
National Heart, Lung, and Blood Institute
Federal Building, Room 5C-10
7550 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-4323
 
REFERENCES
 
1.  Bhasher, R. Reitman, D., Socks, H.S., Smith, H., Jr. and Chalmers,
T.C. Loss of Patients in Clinical Trials that measure long-term survival
following myocardial infarction.  Controlled Clin Trials, 1986, 7,
134-148.
 
2.  Dunbar, J. Predictors of Patient Adherence:  Patient
Characteristics.  In Shumaker, S., Schron, E., and Ockene, J. (Eds.) The
Handbook of Health Behavior Change.  NY:  Springer, 1990.
 
3.  Joyce, C.R.B. Patient Cooperation and the Sensitivity of Clinical
Trials.  J. Chron Dis, 1962, 15, 1025-1036.
 
4.  Probstfield, J.L., Russell, M.L., Henske, J.C., Reardon, R.J. and
Insull, W. Successful Program for Recovery of Dropouts to a Clinical
Trial.  Am J. of Med., 1986, 80, 777-784.
 
5.  Sackett D. L. and Haynes, R. B. (eds.) Compliance with Therapeutic
Regimens.  Baltimore:  Johns Hopkins University press, 1976.
 
6.  Urquhart, J. and Chevalley, C. Impact of Unrecognized Dosing Errors
on the Cost and Effectiveness of Pharmaceutical.  Drug Info J., 1988,
22, 363-378.
 
The programs of the Division of Epidemiology and Clinical Applications,
National Heart, Lung, and Blood Institute, and the National Center for
Nursing Research, are identified in the Catalog of Federal Domestic
Assistance, numbers 93.837-93.839 and 93.361, respectively.  Awards will
be made under the authority of the Public Health Service Act, Section
301 (42 U.S. 241) and administered under PHS grants policies and Federal
regulations, most specifically 42 CFR Part 52 and 45 CFR Part 74.  This
program is not subject to the intergovernmental review requirements of
Executive Order 12372, or to a Health Systems Agency review.