NIH Clinical Trials: Various Factors Affect Patient Participation (Letter
Report, 10/30/1999, GAO/HEHS-99-182).

Pursuant to a congressional request, GAO reviewed patient access to
clinical trials sponsored by the National Institutes of Health (NIH),
focusing on: (1) how health insurers' coverage policies and practices
affect patient participation in clinical trials; (2) researchers'
experience in enrolling patients for trials sponsored by the National
Cancer Institute (NCI) and factors that may explain this experience; and
(3) whether NIH has evidence of recent difficulties in enrolling
patients in clinical trials.

GAO noted that: (1) despite policies that generally exclude coverage for
clinical trials, nearly all the insurers that GAO interviewed allow for
exceptions following case-by-case reviews by the insurers' medical
personnel; (2) if coverage is approved, insurers generally agree to pay
the standard, nonexperimental care costs associated with a trial; but
because there is little agreement on which trial services constitute
standard care, payments can vary from insurer to insurer; (3) given the
uncertainty about approval and payment levels, patients and physicians
can be discouraged from seeking prior approval from insurers; (4) most
cancer research centers GAO contacted said that they did not experience
what they considered to be serious difficulties enrolling adequate
numbers of patients for NCI-sponsored clinical trials; (5) but, all the
centers described clinical trials enrollment as challenging because of
the significant administrative burden incurred in dealing with health
insurers about trial coverage and payment issues; (6) paperwork
requirements can be labor-intensive and time-consuming when staff
physicians and nurses must document the necessity of enrolling each
patient and negotiate the specific services and amounts to be paid as
standard care; (7) center representatives also cited an array of
physican- and patient-related factors that affect the availability of
patients for NIH-sponsored clinical trials; (8) NIH has expressed
concern that trial enrollment is declining, but the data provided to GAO
by several of the largest institutes did not document the basis for
NIH's concerns; (9) patient enrollment in the NIH-sponsored clinical
trials for which GAO could obtain data appeared to be meeting the goals
of those trials; (10) in 1998, NIH officials reported to the Office of
Management and Budget that patient participation in trials was a
substantial problem, particularly for cancer trials; (11) they cited
1996 testimony from clinical investigators that managed care seemed to
have affected patient participation in cancer clinical trials; (12)
beyond such anecdotal information, however, NIH does not have
quantitative data that indicate that patient enrollment has slowed or
that trials have been delayed or prematurely closed because of patient
enrollment problems; and (13) NCI is in the process of converting its
existing clinical trial reporting systems to a new consolidated
electronic system, which should support improved trial monitoring.

--------------------------- Indexing Terms -----------------------------

 REPORTNUM:  HEHS-99-182
     TITLE:  NIH Clinical Trials: Various Factors Affect Patient
	     Participation
      DATE:  10/30/1999
   SUBJECT:  Cancer research
	     Medical research
	     Health insurance
	     Claims settlement
	     Health research programs
	     Patient care services
	     Management information systems
IDENTIFIER:  NCI Clinical Trials Program
	     NCI Clinical Data Update System
	     NIH Type II Diabetes Prevention Program
	     NIH Type I Diabetes Prevention Program

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Cover
================================================================ COVER

Report to Congressional Requesters

September 1999

NIH CLINICAL TRIALS - VARIOUS
FACTORS AFFECT PATIENT
PARTICIPATION

GAO/HEHS-99-182

NIH Clinical Trials

(101808)

Abbreviations
=============================================================== ABBREV

  AAHP - American Association of Health Plans
  CDUS - Clinical Data Update System
  DOD - Department of Defense
  FDA - Food and Drug Administration
  HCFA - Health Care Financing Administration
  HMO - health maintenance organization
  IOM - Institute of Medicine
  NCI - National Cancer Institute
  NHLBI - National Heart, Lung, and Blood Institute
  NIDDK - National Institute of Diabetes and Digestive and Kidney
     Diseases
  NIH - National Institutes of Health
  STAR - Study of Tamoxifen and Raloxifene
  VA - Department of Veterans Affairs

Letter
=============================================================== LETTER

B-281108

September 30, 1999

The Honorable James M.  Jeffords
Chairman, Committee on Health, Education,
 Labor, and Pensions
United States Senate

The Honorable Joseph I.  Lieberman
United States Senate

Clinical trials generate the evidence base for decision-making in all
areas of medicine, and they can be especially important for patients
with serious or life-threatening health conditions that have limited
treatment options.  For those patients, participation in a clinical
trial--a formal investigation of the effects of an experimental
intervention on people--may offer the best chance of finding an
effective treatment.  Concerns have been raised that patient access
to trials has become increasingly constrained as the financing of
health care has changed.  These concerns stem, in part, from
researchers' reliance on insurance payments for the standard,
nonexperimental patient care\1 provided in clinical trials as well as
health plans' efforts to minimize their financial exposure.  In
response, the Congress is considering legislation that would require
health plans to pay for the nonexperimental care provided to patients
in federally approved clinical trials. 

At your request, we conducted a review of patient access to clinical
trials sponsored by the National Institutes of Health (NIH). 
Specifically, you asked us to examine (1) how health insurers'
coverage policies and practices affect patient participation in
clinical trials, (2) researchers' experience in enrolling patients
for trials sponsored by the National Cancer Institute (NCI) and
factors that may explain this experience, and (3) whether NIH has
evidence of recent difficulties in enrolling patients in clinical
trials. 

To address these issues, we obtained information from health
insurers, researchers, and NIH officials.  We interviewed medical
directors at 26 private health insurers that together reflect the
distribution of enrollment nationally in preferred provider
organizations, health maintenance organizations (HMO), and
point-of-service plans.  In addition to discussing the indemnity
products offered by some of these plans, we also contacted a large
indemnity plan.  HMOs were further distributed to reflect three size
categories (plans with under 100,000 enrollees, those with 100,000 to
250,000 enrollees, and larger plans) and various model types.  Also,
plans were selected to provide distribution across geographic areas
to include different levels of managed care activity.  We also
interviewed directors or their designees at 11 of the 48
NCI-designated clinical and comprehensive cancer centers that were
chosen to represent different types of institutions as well as
geographic diversity, concerning their trial recruitment experience. 
(App.  I contains a list of health plans and cancer centers that
participated in our review.) Although neither the insurers nor the
cancer centers were statistically representative groups, and thus the
findings from our interviews cannot be generalized, the findings from
these two groups of interviews were consistent.  In addition, we
obtained information from NIH officials and officials at several NIH
institutes on the recruitment and enrollment of trial participants. 
We also reviewed clinical trial monitoring reports.  Finally, we
conducted a review of the health care literature on barriers to
patient participation in clinical trials and spoke with
representatives of patient advocacy organizations.  We performed our
work from September 1998 to August 1999 in accordance with generally
accepted government auditing standards. 

--------------------
\1 Standard, nonexperimental patient care includes those medical
services that patients would receive for their condition regardless
of whether they received the experimental treatment.  Such services
include physician visits and prescription drugs, for example.  While
there is not complete agreement on which particular services
constitute standard, nonexperimental care for any particular
condition, there is agreement that such care should be provided to
patients.  In this report we refer to this care as ï¿½standard care.ï¿½

   RESULTS IN BRIEF
------------------------------------------------------------ Letter :1

While policies generally exclude coverage for clinical trials, nearly
all the insurers we interviewed allow for exceptions following
case-by-case reviews by the insurers' medical personnel.  If coverage
is approved, insurers generally agree to pay the standard,
nonexperimental care costs associated with a trial; but because there
is little agreement on which trial services constitute standard care,
payments can vary from insurer to insurer.  Given the uncertainty
about approval and payment levels, patients and physicians can be
discouraged from seeking prior approval from insurers.  Insurers
report that they receive few requests for clinical trial coverage and
that they do not maintain data to separately track such requests. 
Yet, insurers may pay for medical care in trials because they are
unaware it is provided in a research context. 

Most cancer research centers we contacted said they did not
experience what they considered to be serious difficulties enrolling
adequate numbers of patients for NCI-sponsored clinical trials.  But
all the centers described clinical trial enrollment as challenging,
in part because of the significant administrative burden incurred in
dealing with health insurers about trial coverage and payment issues. 
Paperwork requirements can be labor-intensive and time-consuming when
staff physicians and nurses must document the necessity of enrolling
each patient and negotiate the specific services and amounts to be
paid as standard care.  Center representatives also cited an array of
physician- and patient-related factors that affect the availability
of patients for NIH-sponsored clinical trials.  For example,
community physicians may be unaware that clinical trial opportunities
exist or lack the time and resources to evaluate candidates for
trials.  Some patients want the promise afforded by new or untested
treatments but may be unable to participate because of a trial's
eligibility criteria or constraints on patients' time and resources. 
For many other patients, uncertainty about the benefits and risks of
experimental treatments can make clinical trials unattractive. 

NIH has expressed concern that trial enrollment is declining, but the
data provided to us by several of the largest institutes did not
document the basis for NIH's concerns.  Patient enrollment in the
NIH-sponsored clinical trials for which we could obtain data appeared
to be meeting the goals of those trials.  In 1998, NIH officials
reported to the Office of Management and Budget that patient
participation in trials was a substantial problem, particularly for
cancer trials.  They cited 1996 testimony from clinical investigators
that managed care seemed to have affected patient participation in
cancer clinical trials.  Beyond such anecdotal information, however,
NIH does not have quantitative data that indicate that patient
enrollment has slowed or that trials have been delayed or prematurely
closed because of patient enrollment problems.  Information on heart
disease and diabetes trials at two other NIH institutes shows that
most trials were close to meeting their recruiting targets as of the
fall of 1998. 

   BACKGROUND
------------------------------------------------------------ Letter :2

A clinical trial is a method for testing new approaches to disease
prevention, diagnosis, or treatment.  The number of clinical trials
has increased dramatically over the years.\2 NIH and pharmaceutical
companies are the major sponsors of clinical trials that focus on
assessments of new drugs, devices, and vaccines.  NIH-supported
trials also may address prevention strategies and surgical procedures
and may target special populations, such as patients with rare
diseases.  Research groups at academic and other medical centers
typically organize NIH clinical trials, but patients may enter into
trials in a range of settings, including community hospitals and
physicians' offices.  The pharmaceutical industry supports the
majority of large clinical trials that determine therapeutic efficacy
of new drug products.  These trials generally focus on conditions
that affect large numbers of people.  An official of the
Pharmaceutical Research and Manufacturers Association has estimated
that drug trials represent about 75 to 80 percent of all approved
trials in the United States and that pharmaceutical companies sponsor
about 80 percent of all drug trials.  The association also has
estimated that trials of medical devices represent less than 5
percent of all approved trials and that nondrug therapies, such as
new surgical or radiation treatments, represent about 10 percent. 

Many clinical trials provide standard, nonexperimental treatment
along with an investigational drug or procedure.  In cancer care, for
example, trials typically consist of modifications to standard care,
such as an added drug or adjustments to the combination, dosage, and
timing of drugs.  In other trials, there can be significant
variations from standard care, or alternative treatments, such as
surgical lung volume reduction for emphysema or bone marrow and stem
cell transplants for leukemia and other conditions, may be evaluated. 
The cost of care in a trial, relative to the cost of standard care,
depends on the nature of the trial.  A recent study of cancer
chemotherapy trials at the Mayo Clinic found that the additional
costs of clinical trial protocols may not be great:  at 1 year after
trial enrollment, average costs per patient were $24,645 for trial
enrollees compared with $23,964 for comparable patients receiving
standard care.\3 Trials involving treatments such as bone marrow
transplants, however, can be very costly. 

The sponsors of a clinical trial, whether NIH or private industry,
pay for research costs, such as for data collection and management,
research physician and nurse time, tests performed purely for
research purposes, and often the experimental therapy as well.\4
Trial sponsors typically rely on insurers to pay for usual patient
care costs, such as for doctor visits, hospital stays, laboratory
tests, and X rays--costs that are incurred whether a patient is
participating in a trial or receiving standard treatment.  There may
be uncertainty, however, about coverage of extra care costs
associated with clinical trial participation, such as for additional
tests.  Insurers' willingness to pay for medical services associated
with trials may affect patients' ability to participate.  (For a
discussion of clinical trial coverage policies in Medicare, the
Department of Defense, and the Department of Veterans Affairs, see
app.  II.)

In order to increase patients' access to clinical trials, efforts are
under way to strengthen links between research entities and insurers. 
In December 1998, NIH and the American Association of Health Plans
finalized an agreement that encourages member plans, on a voluntary
basis, to refer patients to trials and cover the costs of standard
patient care in NIH-sponsored clinical trials.  Members of the
Congress and the administration have shown interest in requiring
public and private payers to cover standard care costs for insured
individuals enrolled in clinical trials, particularly cancer trials. 
Bills have been introduced in the House and Senate to this end,\5 and
a number of states also have taken action.  In July 1999, the Senate
approved a bill that would require self-funded health plans to cover
standard patient care costs in cancer clinical trials.  The Balanced
Budget Act of 1997 required the Health Care Financing Administration
(HCFA) to contract with the National Academy of Sciences for studies
of extending Medicare benefits in five areas, including standard
patient care in clinical trials.  Under that contract, the National
Academy's Institute of Medicine is examining the current status of
clinical trial reimbursement and may recommend changes in Medicare
policy in a report to be released in November 1999. 

--------------------
\2 For example, between 1975 and 1980, the results of six randomized
controlled trials a year were published in the area of heart disease. 
In contrast, between 1993 and 1997, the results of 149 randomized
controlled trials in the area of heart disease were published each
year. 

\3 See Judith L.  Wagner, Steven R.  Alberts, Jeff A.  Sloan, and
others, ï¿½Incremental Costs of Enrolling Cancer Patients in Clinical
Trials:  A Population-Based Study,ï¿½ Journal of the National Cancer
Institute, Vol.  91, No.  10 (May 19, 1999), pp.  847-53. 

\4 A 1999 survey conducted by the American Society of Clinical
Oncology, a professional society representing cancer physicians and
researchers, showed that research costs per patient ranged from $581
to $5,028 for government trials and from $569 to $6,567 for industry
trials.  NCI paid an average of $750 per patient, while
pharmaceutical companies paid an average of $2,500 per patient. 

\5 Bills on this issue introduced in the 106\th Congress include the
Medicare Clinical Trial Coverage Act of 1999 (H.R.  61) and the
Improved Patient Access to Clinical Studies Act of 1999 (S.  117). 

   INSURERS REPORT COVERAGE OF
   CLINICAL TRIALS ON A
   CASE-BY-CASE BASIS
------------------------------------------------------------ Letter :3

As a general rule, health insurance policies exclude coverage of
clinical trials.  However, most insurers we interviewed indicated
that they allow for exceptions to be made selectively following a
case-by-case review.\6 None of the plans we contacted provided us
with data on the numbers of requests considered or cases approved,
saying they do not track requests for trial coverage or their
disposition separately from other benefit coverage disputes. 

Once coverage is approved, insurers told us they often negotiate
payment amounts for the standard, nonexperimental care given to trial
participants, but insurers vary in how they define ï¿½standard care.ï¿½
Although the uncertainty of insurer approval and payment decisions
may discourage participation in clinical trials, insurers may
unknowingly pay for trial-related care for patients who enroll
without their insurers' explicit approval. 

--------------------
\6 Our findings are similar to those reported in a 1995 NIH study,
prepared at the request of the Congress.  That study was based on a
survey of high-level executives (including vice presidents and
medical directors) of nine major third-party payers representing
indemnity insurers and managed care plans.  See NIH, "Third-Party
Reimbursement Policies for Clinical Trials:  Survey Report"
(Bethesda, Md.:  Jan.  1995). 

      WHILE POLICIES GENERALLY
      EXCLUDE COVERAGE, INSURERS
      CLAIM TO REVIEW AND APPROVE
      SOME TRIAL SERVICES
---------------------------------------------------------- Letter :3.1

Patient participation in NIH clinical trials often depends on prior
approval by insurance plans of the proposed treatment.  Typically,
the request for approval initially is submitted to the insurer's
benefits manager, accompanied by information on estimated charges,
the clinical assessment of the patient, data from the literature on
outcomes, a description of the protocol, and the consent form. 
Denials are routinely appealed by the attending physician to the
medical director of the insurance plan. 

Denials are generally based on the grounds that health insurers
consider clinical trials to be ï¿½investigational and experimentalï¿½
care and, as such, are excluded from coverage.\7 In addition,
insurers sometimes deny coverage because they consider standard
treatment in clinical trials to be ineligible for payment, despite
the fact that most insured patients would be receiving some form of
treatment if they were not in the trial.  According to a leading
expert on patient recruitment for clinical trials, insurers might
deny all coverage for patients participating in a trial of
combination drug therapy for cancer treatment if, for example, one of
the four drugs in a trial was not approved by the Food and Drug
Administration. 

Medical directors for most of the 26 insurance plans in our interview
group reported policies that exclude clinical trials from benefit
coverage, but these medical directors also reported willingness in
some cases to consider coverage for plan members participating in
trials.  Some managed care plans, in addition, have special programs
that support limited patient participation in clinical trials.  One
large national plan, for example, has a terminal illness program that
allows a plan member with a life-threatening illness to be approved
to participate in a clinical trial.\8 Another large plan has
established a nationwide program that refers members needing organ
and bone marrow transplants to selected clinical trials. 

All but one of the plans we contacted reported having a mechanism for
reviewing and approving participation in trials on a case-by-case
basis.  An insurer that covered over 6 million people in managed care
and indemnity plans reported making no exceptions to its exclusionary
policy.  In general, insurers that do make case-by-case decisions
prefer to review requests for clinical trial coverage individually
because they perceive a great deal of variability in trial costs and
quality.  Several medical directors said they are wary of small,
poorly designed clinical trials that may not have been subjected to
rigorous peer review. 

In considering individual patient requests, the plans we interviewed
typically follow decision-making procedures established for
determining coverage of experimental treatments.  At most plans, the
medical directors, an internal committee of physicians, or an
independent panel of medical experts evaluates patient requests for
trial services.  Three plans told us that such coverage decisions are
made by the medical provider groups that make up their networks when
the financial risk has been transferred to those groups under
capitation arrangements, but that patients have the option to appeal
to the plan level.  Insurers we spoke with reported that certain plan
members have access to various types of external review.  The
Medicare program and some states, for example, require that managed
care enrollees have access to an external appeals process if they are
denied care.  In the case of self-insured health plans, the employer,
rather than the plan administrator, may be the final decisionmaker on
requests for clinical trial coverage. 

In conducting their case-by-case reviews, the medical directors
reported considering a range of factors.  The most common
considerations were the scientific merit of the trial and the
anticipated costs.  Although none of the insurers had data on the
cost of covering clinical trials, most perceived trials to be
somewhat more costly than standard treatment.  Medical directors for
19 plans said they would be inclined to approve coverage if a patient
had a life-threatening disease and the experimental treatment offered
some chance of clinical benefit.  About one-third of the insurers
would consider approving a prevention trial for a high-risk patient,
one-third would likely deny such coverage, and the remainder would
decide depending on the circumstances.  Sixteen insurers mentioned
their preference for NIH-sponsored phase III trials,\9 and six
indicated that they would not approve requests to participate in
commercial drug company trials.  Given concerns about the cost of
trials, some insurers said trials conducted by providers in their
networks receive preference.\10 Twenty insurers reported that whether
the trial treatment was provided in an inpatient or an outpatient
setting was unimportant.  Public pressureï¿½as in the case of bone
marrow transplantation for treatment of breast cancerï¿½also has
influenced coverage decisions. 

Medical directors reported that, among the benefit disputes brought
to them for reconsideration, coverage requests for clinical trials
are not common.  Cancer treatment is the most frequently requested
type of clinical trial.  Although plans generally do not track the
number of clinical trial requests or their disposition, estimates
ranged from as few as two cases per year at one plan with 180,000
members to several hundred requests per year at another with an
enrollment of 10 million. 

--------------------
\7 Coverage policies, including those dealing with investigational
and experimental treatments, are specified in the contracts between
the insurer and the purchaser of the insurance, which is usually an
employer. 

\8 In December 1998, this plan also agreed to participate in an
NIH-supported cancer coalition demonstration project to study the
costs for members enrolled in cancer prevention and treatment trials. 
During the first 6 months, only one patient participated in this
program; a second patient is undergoing eligibility review. 

\9 Phase III trials involve relatively large patient populations
(perhaps hundreds or thousands) and are designed to confirm benefits
and risks and to compare the efficacy of new therapies with that of
standard treatments. 

\10 All 11 of the cancer centers we contacted participate in managed
care networks in their areas.  Only three reported that one or more
of the networks in their areas currently refuse to refer patients to
their centers. 

      INSURERS REPORT VARIATIONS
      IN HOW THEY DECIDE WHICH
      TRIAL SERVICES TO COVER AS
      STANDARD CARE
---------------------------------------------------------- Letter :3.2

Once insurers decide to cover services provided in clinical trials,
they decide which services should be covered and at what payment
amounts.  Nearly all of the insurers we spoke with said that they pay
standard care costs for approved trial participants.  However, there
is little agreement on which trial services constitute standard care,
and, therefore, payment for services provided in a trial can vary
widely.  Moreover, insurers may not always be aware when services are
provided in the context of a trial. 

Insurers we interviewed stated that it is often difficult to
distinguish expenses that constitute standard care--those services
that otherwise would have been provided to the patient, absent the
trial--from strictly research-related services.  For example,
physician visits and laboratory tests are components of standard care
that would be covered by the insurer outside a trial.  While the
frequency of these services may increase in a trial to more closely
monitor the patient, separately identifying claims for these
additional services may be difficult.  Similarly, disputes may arise
if a patient has an adverse reaction to an investigational drug and
requires an emergency room visit or additional treatment.  While 14
insurers in our group said they would cover the cost of treating
medical complications, 7 said it would depend on the situation, and 4
said they would not pay for services needed to treat research-related
complications. 

Several insurers said they found it too burdensome to try to separate
trial costs from standard care costs in the relatively few cases at
issue.  Therefore, once they have approved participation in a
clinical trial, they generally pay all patient care costs.  More
commonly, however, insurers negotiate what services they will cover
in clinical trials and how much they will pay for them.  Many
insurers we talked with said they negotiate with trial researchers
regarding payments for each individual case and, therefore, payments
can vary considerably.  In some cases, insurers negotiate an overall
fee, or case rate, while in other cases they use network fee
schedules, such as discounted fee-for-service rates.  Typically,
patients are responsible for any deductibles and copayments required
under their benefit contracts. 

Trials conducted by providers outside of plans' networks complicate
these payment issues.  Managed care plans may negotiate or even
contract for coverage of an individual patient or ask the
out-of-network trial provider to accept in-network provider rates. 
Many insurers we contacted encourage the use of their own network of
health care facilities and trial providers to hold down costs.  The
cost of obtaining a magnetic resonance image in a research setting,
for example, may be considerably higher than the cost of performing
the procedure in a facility under contract with the managed care
plan. 

Some of the medical directors we spoke with believe that, in many
cases, patients enroll in trials without prior authorization by their
plans.  Moreover, these medical directors acknowledged that the plans
may make payments without knowing that the care was provided in the
context of a clinical trial.\11 The directors could not estimate the
extent to which this happens but suggested that it could happen
frequently.  Similarly, officials of the NCI cancer centers we
interviewed reported that all types of insurers, including public
payers, pay some claims for patients who are treated in clinical
trials at their centers.  In 1997, we surveyed physicians and found
that Medicare reimbursed certain trial costs despite a general policy
not to cover patient care associated with clinical trials.  Of 186
physicians responding, all but one received Medicare reimbursement
for patients in cancer trials.\12

--------------------
\11 This observation was previously reported in Robert Mechanic and
Allen Dobson, ï¿½The Impact of Managed Care on Clinical Research:  A
Preliminary Investigation,ï¿½ Health Affairs, Vol.  15, No.  3 (fall
1996), pp.  72-89.  Another way that plans may cover care in trials
without specifically authorizing it is by including academic health
centers, which are known to enroll patients in trials, in their
provider networks. 

\12 Cancer Clinical Trials:  Medicare Reimbursement Denials
(GAO/HEHS-98-15R, Oct.  14, 1997). 

   RESEARCHERS MEET TRIAL
   ENROLLMENT NEEDS DESPITE MANY
   CHALLENGES THAT CAN DISCOURAGE
   PATIENT PARTICIPATION
------------------------------------------------------------ Letter :4

A shortage of patients for NCI-sponsored clinical trials does not
appear to be a significant problem at most of the cancer research
centers we contacted.  Nonetheless, all of the centers reported
incurring a significant administrative burden when dealing with
health insurers over trial coverage issues for patients on a
case-by-case basis.  In addition, center officials cited a number of
physician- and patient-related factors that can influence clinical
trial participation. 

      CANCER CENTERS REPORT
      ADEQUATE NCI TRIAL
      ENROLLMENT ALONG WITH SOME
      PAYMENT DIFFICULTIES
---------------------------------------------------------- Letter :4.1

Most of the NCI-designated cancer centers we contacted report they
are able to enroll adequate numbers of patients to conduct
NCI-sponsored trials, but recruitment is not without its
challenges.\13 Cancer center representatives reported a range of
experiences in obtaining health plan coverage for patients enrolled
in trials and said that the process is time-consuming and
labor-intensive.  According to most centers, third-party payments
generally cover the standard care provided to trial participants but
are less consistent in covering extra care costs associated with
trials. 

Officials at 8 of the 11 NCI-designated cancer centers we contacted
around the country reported that they were not having serious
difficulties enrolling an adequate number of patients in
NCI-sponsored clinical trials.\14 Many centers estimated that 10 to
30 percent of their patients were participating in trials.  Three
centers reported experiencing what they considered to be serious
difficulties enrolling patients, including a variety of marketplace
and clinical factors; but generally the centers were working to
overcome those difficulties.  Center officials cited only two
examples of trials that were closed prematurely because of enrollment
problems:  a costly liver infusion trial and a trial of bone marrow
transplantation for a serious connective tissue disease. 

Nearly all the cancer center officials we interviewed reported some
degree of difficulty in dealing with insurers over clinical trial
coverage, but they generally characterized these difficulties as
ï¿½business as usual.ï¿½ These officials said their experiences varied
with the individual insurers in their areas:  some rejected requests
for coverage, some paid fully for standard care in trials, and others
frequently denied coverage for specific services.  Center physicians
and staff reportedly spend considerable time and effort dealing with
insurance issues for patients in trials.  Research physicians are
required to document that the trial is medically necessary and to
provide other information to justify enrollment in a trial. 
Officials at two centers explained that efforts to obtain coverage
were enhanced when they could provide data showing that the cost of
patient care in certain cancer trials was the same as or less than
that of care provided outside of trials.  Other officials noted that
some patients at NCI-designated centers get insurance approval for
trials because they know how to appeal an initial denial.  It is
rare, another official said, for a persistent patient to be denied
coverage, because some accommodation usually is made to pay for
services.  As a result of these efforts, officials reported that
insurers usually agreed to cover patients in trials at their centers. 

Center officials stated that insurers that approve coverage generally
pay for the standard care provided to trial participants.  Most of
the centers in our group are able to separately identify and exclude
research costs (such as trial organization, administration, and data
collection) and bill insurers for standard care.  Insurers typically
pay the centers under the same arrangements that apply to patients at
the centers who are not in trials--for example, discounted
fee-for-service charges or limited case rate payments. 
Representatives of two centers specifically stated that the payments
they received from insurers were insufficient to cover the costs of
standard care involved in trials.  In addition to payments from
private health plans, the cancer centers reported that Medicare and
Medicaid also paid claims for patients in their clinical trials. 

It is not uncommon for managed care plans to require that laboratory
and other testing services related to trials be performed at
facilities in the plans' networks.  Some cancer center researchers we
interviewed contend that the inconvenience of having to visit several
sites of care discourages patient participation. 

--------------------
\13 All of the centers conducted a mix of NCI- and pharmaceutical
industry-sponsored trials, with NCI-sponsored trials predominating. 

\14 Individual cancer centers in our contact group reported total
numbers of open clinical trials ranging from roughly 60 to more than
400.  Numbers of patients enrolled in these trials ranged from about
350 to 450 at some centers to 1,000 to 2,000 at others. 

      MANY FACTORS OTHER THAN
      INSURANCE COVERAGE INFLUENCE
      PATIENT PARTICIPATION IN
      TRIALS
---------------------------------------------------------- Letter :4.2

Our cancer center interviews and the research literature indicate
that many factors, in addition to insurance coverage practices, can
influence patient participation in clinical trials.  For example,
physicians are often unaware of relevant trials or unable to meet the
time and resource demands associated with enrollment activities.  In
addition, many patients are not interested in enrolling in trials. 
Other patients face eligibility limitations or logistical barriers,
or are reluctant to participate in a randomized experiment.  The
influence of these various factors depends on the type of disease,
type of trial, phase of trial, and other unique circumstances. 

         PHYSICIAN AWARENESS AND
         RESOURCES
-------------------------------------------------------- Letter :4.2.1

Because patients rely heavily on their physicians to inform and
advise them about treatment options, physicians are often the most
influential factor in a patient's decision to participate in a
clinical trial.  However, physicians and other health care providers
can be unaware of the opportunities for participation in clinical
trials.  Decisions regarding enrollment in trials are made locally by
physicians, hospitals, and health plans and, as a result, promotion
of trials within the medical community is considered key.\15 Some
cancer center officials we interviewed contend that managed care
patients may not be referred to specialist physicians, who are most
likely to be aware of clinical trial opportunities in their area. 
These officials reported more intensive efforts to make patients
aware of trials directly, through Internet Web sites, media
advertising, and other strategies. 

Officials we interviewed from 8 of the 11 cancer centers, as well as
oncologists recently surveyed by the American Society of Clinical
Oncology, indicated that constraints on physicians' time, available
research resources, and administrative support are significant
factors affecting participation.  The burden on physicians often
includes the need to devote additional time to identifying and
enrolling suitable individuals as well as the extra paperwork
involved in recording baseline data and screening candidates.  In a
study conducted by NCI to explore reasons for low enrollment in
certain breast cancer trials, community-based oncologists cited the
following issues:  the time it takes to obtain consent and to attend
to ongoing paperwork, to explain trial criteria to the patient, and
to learn the protocol; the lack of uniform standards; and the burden
and expense of performing numerous tests and following up with the
patient.\16

--------------------
\15 According to the mandate of the Food and Drug Administration
Modernization Act of 1997, NIH is responsible for developing a
ï¿½one-stop shoppingï¿½ clinical trials database that eventually will
include information on publicly and privately funded clinical trials
for drugs for life-threatening diseases and conditions. 

\16 NCI, Office of Cancer Communication, ï¿½Patient Referral to the
National Cancer Institute's Autologous Bone Marrow Transplantation
Clinical Trials:  The Physician's Perspectiveï¿½ (Bethesda, Md.:  Aug. 
1995). 

         PATIENT ELIGIBILITY,
         LOGISTICS, AND ATTITUDES
-------------------------------------------------------- Letter :4.2.2

Patients who are motivated to participate in clinical trials often
perceive them as an opportunity to receive superior care and make a
contribution to medical knowledge.  However, these patients can be
held back by the narrow eligibility criteria used to select study
subjects, or discouraged by logistical considerations or their own
apprehensions about medical experimentation. 

According to the 1999 American Society of Clinical Oncology's survey
of oncologist opinion, strict trial eligibility criteria are the
ï¿½single greatest barrierï¿½ to enrolling patients in trials.  Patient
eligibility criteria (such as the type and stage of disease under
investigation and absence of other medical conditions) are necessary
to define study populations and support reliable conclusions. 
However, when these criteria are very restrictive, they act as
barriers to patient access.  In 1997, the NCI Clinical Trials Program
Review Group reported that there were too many exclusion criteria in
the cancer clinical trials system, with the result that potential
enrollees were being disqualified for seemingly arbitrary reasons
from trials for which they would otherwise qualify.\17 A related
concern is that researchers may be inclined to select subjects who
are likely to provide the best trial outcomes.  A recent study of
high-dose chemotherapy for breast cancer showed that, in identifying
candidates for a trial, clinicians limited referrals mostly to
patients who had the best chance of survival.\18

Logistical concerns can also influence patients' decisions about
whether to enter trials.  In some cases, participation in a trial may
require traveling to a distant trial site and, possibly, staying
overnight or longer.  Such requirements can be time-consuming and
impose financial and child care burdens on individuals who may be
seriously ill.  Moreover, such demands can add to stress by
separating patients from family support and making it difficult to
meet work obligations.  As one cancer center official told us, many
of life's practical concerns are magnified in a clinical trial,
because trials place more requirements on and offer less flexibility
to the patients. 

In addition, eligible patients may choose not to enroll in clinical
trials because of their personal preferences for certain types of
care or their limited understanding of the clinical trials system. 
Sound research design requires that clinical studies minimize bias by
random assignment of patients to treatment and control groups.  But
patients who view the experimental intervention as their best hope
for treatment may be reluctant to participate if they cannot be
assured they will receive what they believe to be superior care. 
Further, difficulty with the informed consent process can be a
factor; even patients who want to participate in clinical trials may
feel overwhelmed by the treatment decision-making process involved in
informed consent.  According to the NCI Clinical Trials Program
Review Group report, this process has become ï¿½a disclaimer for
institutions rather than information for the participantï¿½ and ï¿½may be
inappropriately deterring individuals from participating in clinical
trials.ï¿½ Finally, a lack of trust in medical research can make
patients unwilling to participate.  Several of our cancer center
officials said that, combined with language and cultural barriers,
this lack of trust can make it especially difficult to recruit
minority populations. 

--------------------
\17 NCI, ï¿½Report of the National Cancer Institute Clinical Trials
Program Review Groupï¿½ (Bethesda, Md.:  Aug.  26, 1997).  This study
is often referred to as the Armitage report, after the panel's
chairman, James O.  Armitage, M.D. 

\18 Z.U.  Rahman, D.K.  Frye, A.U.  Buzdar, and others, ï¿½Impact of
Selection Process on Response Rate and Long-Term Survival of
Potential High-Dose Chemotherapy Candidates Treated With
Standard-Dose Doxorubicin-Containing Chemotherapy in Patients With
Metastatic Breast Cancer,ï¿½ Journal of Clinical Oncology, Vol.  15,
No.  10 (Oct.  1997), pp.  3171-7. 

   NIH HAS LITTLE EVIDENCE OF
   PROBLEMS WITH PATIENT
   ENROLLMENT IN TRIALS
------------------------------------------------------------ Letter :5

Citing anecdotal reports, NIH contends that insurer resistance to
covering services has contributed to a significant decline in
clinical trial enrollment.  Yet we received little quantitative data
from NIH to indicate that fewer patients are entering NIH-sponsored
trials or that more trials are being delayed or cancelled.  NIH does
not maintain a centralized tracking system on the number of people
who enroll in clinical trials each year, overall, or by institute. 
Therefore, we contacted some of the institutes with the most clinical
trial activity for information about patient enrollment.  The
institute sponsoring the most clinical trial activity, NCI, could not
provide reliable data to demonstrate growing difficulties in
enrolling patients in cancer trials.  Officials of another large
institute we contacted, the National Heart, Lung, and Blood Institute
(NHLBI), reported no major new difficulties in meeting patient
enrollment needs; in fact, NHLBI's monitoring data on heart disease
trials showed that most were enrolling patients at or above 80
percent of target levels.  In its data system for monitoring trial
enrollment, NHLBI considers meeting 80 percent of target levels good
progress in recruiting.  Moreover, data from the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK) showed diabetes
trials enrolling at or above target levels in 1998. 

      NCI IS CONCERNED ABOUT
      DIFFICULTIES IN ENROLLING
      PATIENTS IN CANCER TRIALS
---------------------------------------------------------- Letter :5.1

In a 1998 paper prepared for its fiscal year 2000 budget submission
to the Office of Management and Budget, NIH stated that increased
resistance by insurers to covering standard care costs for trial
participants had slowed patient enrollment and led to longer
studies.\19 Among the NIH officials we contacted, NCI officials
expressed the greatest concerns about increased difficulties
enrolling patients in clinical trials.  Citing testimony before the
President's Cancer Panel at four regional hearings in 1996, NCI
officials indicated that insurers do not want to pay for standard
care associated with clinical trials, and, as a result, ï¿½the type and
number of patients that get into a trial are changed; the type of
clinical trial that is conducted is changed; and the speed of the
trial is changed.ï¿½\20

Although NIH has asserted that there is a crisis in patient
participation in clinical trials, NCI officials could not provide
reliable patient enrollment data that would enable us to determine
whether enrollment in trials was declining or whether actual
enrollment lagged significantly from planned enrollment levels.\21
NCI is currently developing a standardized electronic monitoring
system to track an array of clinical trial data, including planned
and actual patient enrollment.  However, NCI officials told us that
the new reporting system, known as the Clinical Data Update System
(CDUS), did not capture information on all cancer trials.  For
example, it included studies by cooperative groups and some
individual investigators but not those conducted at NCI-funded cancer
centers.  CDUS developers reported that, in converting historical
data from an earlier monitoring system, they had experienced
difficulties with the reporting of enrollment information.  In
addition, only a few data submissions had been audited since the
system was implemented.  Because these data were not complete or
adequately verified, we could not determine whether patient
enrollment had slowed or trials have been delayed. 

--------------------
\19 NIH, ï¿½Current Structure of NIH Support for Clinical Trials: 
Responses to Questions for the Fiscal Year 2000 OMB Budget
Submission" (Bethesda, Md.:  Aug.  1998). 

\20 President's Cancer Panel, "Fighting the War on Cancer in an
Evolving Health Care System" (Bethesda, Md.:  NCI, 1997). 

\21 To examine trends in overall enrollment, we requested data on all
cancer trials from 1994 to 1998.  To examine delays in meeting
enrollment targets, we requested planned and actual enrollment data
on breast and prostate cancer trials recruiting patients during 1997
and 1998. 

      EVIDENCE FROM OTHER
      INSTITUTES SHOWS LITTLE
      PROBLEM WITH ENROLLMENT
---------------------------------------------------------- Letter :5.2

The NHLBI at NIH also has a high level of clinical trial activity. 
NHLBI officials told us that, while recruitment challenges are always
present, in general the Institute has not experienced major new
difficulties in meeting patient enrollment needs.  Specifically,
officials noted that in the few cases in which they found enrollment
lagging behind schedule, they were able to provide researchers with
additional funds to help them meet recruitment targets.  Factors
influencing patient recruitment have not changed substantially over
the past 20 years, officials told us, although NHLBI does now compete
more actively for patients with trials sponsored by the
pharmaceutical industry. 

NHLBI monitoring data support these assertions.  When NHLBI's
Division of Heart and Vascular Diseases reported third-quarter 1998
monitoring data on 19 heart trials, of 13 trials that had been
recruiting for at least a year, 6 were at or above 100 percent of
their patient recruiting targets; 4 were at 80 to 99 percent of their
targets; and 3 were below 80 percent of their goals.\22

From the Division of Epidemiology and Clinical Applications we
received mid-1998 recruitment data on six heart trials that had been
recruiting for at least a year.  The data showed that two trials were
at or above 100 percent of their targets, three were at 80 to 99
percent of their targets, and one was slightly below 80 percent. 
Recruitment report notes stated that this last trial is expected to
finish within budget and on time. 

We also contacted NIDDK.  In 1997-98, two large phase III trials were
recruiting patients with diabetes, the leading area of NIDDK
research.  The Diabetes Prevention Program--Type II (seeking 3,000
individuals at high risk for developing non-insulin-dependent
diabetes) reported that, as of December 1998, the total number of
participants exceeded the target recruitment level.  Specific data on
21 participating clinical centers showed that 10 clinics had
recruited over 100 percent of their goals, 9 had achieved between 80
and 99 percent of targets, and 2 were at 70 to 79 percent of their
goals. 

NIDDK officials told us that the Diabetes Prevention Trial--Type I
(enrolling individuals at high risk for developing insulin-dependent
diabetes) was having difficulty with recruitment.  A progress report
from the trial coordinating center noted that, because only a small
percentage of people are eligible to participate, the trial needs to
screen an estimated 80,000 to 100,000 individuals to identify 830
participants.  As of November 1998, 441 were enrolled in the
study--mostly people under age 20.  Officials also noted that low
payments to physicians--$10 for each screened patientï¿½may be
discouraging physician referrals to this trial. 

--------------------
\22 Reports on new patient enrollment in 1997 and 1998 included
recruitment start and stop dates, target enrollment and actual
enrollment (cumulative to date and tracked against quarterly targets
on a graph), and actual minority and female enrollment compared with
targets. 

   CONCLUSIONS
------------------------------------------------------------ Letter :6

We did not find evidence of widespread limitations on patient access
to clinical trials.  Most health insurers we interviewed said they
allow for coverage of trials in some circumstances, most cancer
centers we interviewed reported no shortage of patients for trials,
and NIH did not document significant trial enrollment problems. 
Nevertheless, information on the extent to which insurers cover
clinical trials is not clear-cut.  On the one hand, having to seek
approval through a plan's review and appeals process and negotiating
payment for standard care in a trial may dissuade some patients and
physicians from pursuing clinical trial opportunities.  On the other
hand, because of the perceived obstacles associated with obtaining
insurance coverage, some patients and physicians may submit claims
without identifying the services as trial-related.  Consequently,
insurers may be covering more trial services than they officially
approve.  Moreover, in addition to insurance coverage, there are many
patient- and physician-related factors that affect patient
participation in clinical trials. 

   AGENCY AND OTHER COMMENTS
------------------------------------------------------------ Letter :7

We provided a draft of this report for comment to the Institute of
Medicine (IOM), the American Association of Health Plans (AAHP), and
NIH.  The IOM and AAHP generally concurred with the information
presented and offered technical suggestions that we have incorporated
as appropriate.  The IOM reviewer, for example, stated that our
findings are consistent with information gathered over the past year
for an IOM report looking at overlapping issues (related specifically
to Medicare). 

NIH disagreed with our conclusion that evidence of widespread
limitations on patient access to NIH-supported clinical trials is
lacking, stating that our study design was flawed and our results are
not generalizable.  In general, NIH officials argued that we should
have broadened the scope of the study to include a greater number and
wider range of insurers, research institutions, and investigators, as
well as physicians and patients.  We recognize that NIH clinical
trials involve a prescribed patient population, physicians,
investigators, and academic and other medical centers, and that
patients may be entered into trials in a range of settings, including
community hospitals.  However, we focused our work on three key
participantsï¿½health insurers, cancer centers, and several of the
largest trial-sponsoring institutes at NIHï¿½because they are in a
strong position to illuminate the range of factors that influence
patient participation in clinical trials, and to provide evidence of
recent difficulties, if any, in enrolling patients for NIH-sponsored
clinical trials. 

Specifically, NIH argued that our data collection efforts were
insufficient on several counts:  (1) the 26 managed care and
indemnity insurance plans we interviewed represent a small,
nonrepresentative sample; (2) in addition to interviewing officials
at NIH-designated cancer centers, we should have included community
physicians who participate in cooperative groups, generalist and
specialist physicians who do not regularly refer patients to trials,
and researchers who did not receive NIH funding; (3) we should have
surveyed patients to determine factors that influence their decisions
to enroll in clinical trials; (4) in addition to gathering data about
insurance policies, we should have documented health plans' policies
on physician referral patterns and productivity; (5) we should have
used additional data from NCI on actual and projected enrollment for
clinical trials; and (6) we should have documented the need for
additional resources to recruit patients into trials. 

As we noted in the report, the results of our insurer and cancer
center interviews should not be generalized because these groups were
not statistically representative.  Nonetheless, the information
reported to us by health plan medical directors and cancer center
directors was consistent.  Insurers were selected to represent a
variety of plan types, sizes, and geographic areas, and they included
many large, nationwide plans.  The cancer centers likewise reflected
geographic diversity and different levels of managed care activity. 

We did not seek out researchers and physicians who were not
successful in obtaining NIH funding for proposed clinical trials. 
There are many reasons that researchers' proposals do not receive
support from NIH, and a perceived inability to recruit a sufficient
number of research subjects may play a role in the funding decision. 
However, our focus was on factors that affect the ability of patients
to participate in trials that do receive funding from NIH institutes,
and by and large, the cancer centers we contacted reported no major
difficulties enrolling patients into trials. 

A survey of patients with cancer or other serious diseases would have
been especially problematic, given concerns about confidentiality of
medical information.  Instead, we discussed with cancer center
directors the patient-related barriers to participation, reviewed the
literature on factors that affect patient enrollment in clinical
trials, and interviewed patient advocacy groups.  From these sources,
we learned that trial eligibility criteria can limit patient access,
and practical matters such as additional demands on patients' time
and resources, as well as uncertainty about the benefits and risks of
experimental treatments, sometimes discourage patients from
participating in trials. 

A review of health plans' policies on physician referral rates and
productivity was beyond the scope of our study.  The results of a
recently completed survey by the American Society of Clinical
Oncology may shed light on these issues when published later this
year.  Other research is under way to develop data on several other
aspects of the clinical trials issue, including the impact of managed
care on academic health centers' ability to do clinical research. 

We asked NCI for data that would enable us to determine whether (1)
overall enrollment in cancer trials declined over the past 5 years
and (2) recent breast and prostate cancer trials were meeting patient
enrollment targets or were requiring more time than planned to do so. 
Although NCI provided partial data to us, we decided that the data
were not usable for assessing patient enrollment patterns.  In
discussions between our statisticians and the head of the Drug
Management and Authorization Section of the Cancer Therapy Evaluation
Program and other NCI officials, our data experts determined that the
NCI data system is in transition and the trial-specific database was
incomplete, inconsistent, and had not been adequately verified.  We
therefore concluded that NCI did not have reliable, quantitative
information documenting problems on patient enrollment. 

In discussions with NCI, NHLBI, and NIDDK, none of these institutes
cited an increasing use of administrative supplements as an indicator
of enrollment problems.  Officials at one of the smaller institutes,
the National Institute on Aging, reported that it had been forced to
add additional funds to clinical trial grants to support more
extensive minority patient recruitment efforts than anticipated. 
However, they said that, in general, investigators were not
experiencing major patient enrollment problems. 

Appendix III contains the general comments received from NIH.  In
addition, the agency provided a number of specific suggestions, many
of which are reflected in the final report. 

---------------------------------------------------------- Letter :7.1

As agreed with your offices, unless you publicly announce its
contents earlier, we plan no further distribution of this report
until 30 days after the date of the report.  At that time, we will
send copies to interested parties and make copies available to others
upon request. 

Please call me at (202) 512-7119 if you or members of your staff have
any questions about the information in this report.  Other
contributors to this study include Rosamond Katz, Ellen M.  Smith,
Margaret Buddeke, and Jennifer Grover. 

Janet Heinrich
Associate Director, Health Financing
 and Public Health Issues

HEALTH PLANS AND CANCER CENTERS
INTERVIEWED
=========================================================== Appendix I

INDIVIDUAL HEALTH PLANS

We selected individual health plans to represent a variety of plan
types--HMO, preferred provider organization, or point-of-service
option--and we asked plan medical directors to focus on that selected
type of plan in our interviews.  However, most of the respondents
reported that the same policies regarding patient participation in
clinical trials generally apply to all of the plan types they offer,
including indemnity plans. 

Advantage Care, Inc.
Lexington, KY

Alliance Health Network
Erie, PA

Allina/Medica Health Plans
Minneapolis, MN

Blue Cross of Idaho
Boise, ID

CAPP-Care, Inc.
Newport Beach, CA

Empire Blue Cross Blue Shield
New York, NY

First Health Group, Inc.
Downers Grove, IL

George Washington University Health Plan
Washington, DC

Group Health Cooperative of Puget Sound
Seattle, WA

Group Health Northwest
Spokane, WA

Harvard Pilgrim Health Care
West Brookline, MA

Highmark Blue Cross Blue Shield
Pittsburgh, PA

M Plan
Indianapolis, IN

Pacificare of Oklahoma
Tulsa, OK

Pacificare of Washington
Seattle, WA

Penn State Geisinger
Danville, PA

PHP Companies, Inc.
Knoxville, TN

PHP of Northern Indiana
Fort Wayne, IN

Presbyterian Health Plan
Albuquerque, NM

QualChoice Health Plan, Inc.
Cleveland, OH

ViaHealth
Rochester, NY

CORPORATE HEADQUARTERS

Aetna US Healthcare
Blue Bell, PA

CIGNA HealthCare
Bloomfield, CT

Kaiser Permanente Regional Office
Oakland, CA

Pacificare Health Systems
Santa Ana, CA

United Healthcare, Inc.
Minneapolis, MN

CANCER CENTERS

Barbara Ann Karmanos Cancer Institute
Wayne State University
Detroit, MI

The Cancer Institute of New Jersey
Robert Wood Johnson Medical School
New Brunswick, NJ

Cancer Research Center
Albert Einstein College of Medicine
Bronx, NY

Cancer Research Center
University of Chicago
Chicago, IL

Chao Family Comprehensive Cancer Center
University of California at Irvine
Orange, CA

Comprehensive Cancer Center
Bowman Gray School of Medicine
Wake Forest University
Winston-Salem, NC

Comprehensive Cancer Center
Yale University School of Medicine
New Haven, CT

Fred Hutchinson Cancer Research Center
Seattle, WA

H.  Lee Moffitt Cancer Center and Research Institute
University of South Florida
Tampa, FL

Johns Hopkins Oncology Center
Baltimore, MD

Lombardi Cancer Research Center
Georgetown University Medical Center
Washington, DC

USC/Norris Comprehensive Cancer Center
University of Southern California
Los Angeles, CA

CLINICAL TRIAL COVERAGE IN FEDERAL
HEALTH PROGRAMS
========================================================== Appendix II

Federal health programs vary in how they cover services provided in
clinical trials sponsored by the National Institutes of Health (NIH). 
The Medicare program and the Department of Defense's (DOD) TRICARE
program--both large payers--generally exclude coverage for unproven
therapies, including clinical trials.  The Department of Veterans
Affairs (VA) and DOD's direct care system have actively promoted
biomedical research for decades.  VA and DOD have expanded their NIH
research affiliations by developing agreements with the National
Cancer Institute (NCI) to increase beneficiary access to NCI clinical
trials. 

MEDICARE

Administered by the Health Care Financing Administration (HCFA),
Medicare insures 38.6 million elderly and disabled beneficiaries. 
Medicare's policy is that, to be covered, services must be reasonable
and necessary for diagnosis and treatment of disease or injury, and
they may not be experimental or investigational.  Medicare does make
some exceptions to its general policy not to cover patient care costs
in clinical trials, particularly in the area of medical devices.\23
On the basis of a 1995 agreement between HCFA and the Food and Drug
Administration (FDA), patients participating in trials of most
devices that have FDA-approved Investigations Device Exemptions are
eligible for Medicare payment.  For example, patients receiving
investigational pacemakers or defibrillators that are refinements of
approved devices may be covered under the standard Medicare
diagnosis-related group system that pays for both the device and the
implantation procedure. 

In practice, it appears that Medicare pays for a considerable amount
of care provided in clinical trials.  Since Medicare billing
practices do not distinguish clinical trial services from standard
care services, HCFA does not know how much investigational care is
being reimbursed.  If a patient receives chemotherapy for cancer, for
example, the Medicare contractor may not know if it is provided in
the context of a clinical trial.  Similarly, the diagnosis-related
group system for reimbursing hospital care prevents Medicare from
knowing if a patient is participating in a clinical trial.  HCFA
would only know a clinical trial was under way if the provider
purposefully notified HCFA or if an exceptional claim for
reimbursement for experimental care drew attention during claims
processing. 

For the first time, HCFA has recently decided to provide conditional
coverage of an emphysema clinical trial that examines the
effectiveness of lung reduction surgery as a treatment.  This
National Heart, Lung, and Blood Institute multicenter trial has
screened about 1,600 patients, and nearly 400 have enrolled so far. 
An NIH official, estimating that the surgery will cost approximately
$30,000 per case, told us that this demonstration project provides a
good research model for third-party payers participating in clinical
trials. 

Under a HCFA contract, the Institute of Medicine (IOM) is conducting
a study of routine patient care costs that could be incurred in
clinical trials involving Medicare beneficiaries.  The IOM report,
which is expected to be released in November 1999, will recommend
criteria that HCFA can use to determine both which services
associated with clinical trials to cover as well as what Medicare
payment levels should be. 

DOD

The DOD health care system, administered by the TRICARE Management
Activity and the Army, Navy, and Air Force, provides both direct care
and contracted care for 8.2 million individuals.  DOD policy excludes
coverage of services considered to be unproven and restricts coverage
to safe and effective treatments, but DOD does conduct medical
research in its network of military treatment facilities and, since
1996, has participated in NCI clinical trials. 

DOD officials relaxed the clinical trial coverage limitation in 1996
to permit access to NCI-sponsored clinical trials during a 3-year
demonstration project, which was extended in June 1999.  The purpose
of the NCI-DOD Clinical Trials Demonstration Project is to support
and expand the clinical trials conducted at the military treatment
facilities and to provide beneficiaries with access to NCI clinical
trials at civilian institutions. 

During the first 3 years of the project, 206 patients participated in
NCI-sponsored clinical trials.  Over half of these patients received
care for breast cancer, which, according to DOD officials, indicates
that the agreement has so far been a vehicle for providing access to
high technology, such as bone marrow transplantation.  For instance,
all patients who meet the eligibility requirements are automatically
accepted into a clinical trial, and they receive the transplant
without risk of being assigned to a control group.  However, overall
participation has been lower than expected, which has created a delay
in evaluating the project:  DOD officials told us that they plan to
increase participation by raising awareness through education
efforts.  DOD officials also reported that NCI will be conducting a
demonstration project evaluation that will examine access and cost
issues.  Meanwhile, the new 1999 DOD agreement with NCI extends
coverage to prevention clinical trials, such as the nationwide breast
cancer prevention trial known as STAR (Study of Tamoxifen and
Raloxifene), as well as to cancer early detection trials. 

VA

A direct care provider for nearly 3 million veterans, VA actively
promotes intramural and extramural medical research.  Fifty-two VA
medical centers maintain research affiliations with NCI, and VA
collaborates on clinical research with several other NIH institutes,
pharmaceutical companies, DOD, and the Department of Health and Human
Services.  Supported by a research budget of over $1 billion, VA
announced a major expansion of its clinical trial program in 1999. 

In 1997, VA reported that cancer was the second leading cause of
death among veterans.  At that time, about 170,000 veterans were
affected, and approximately 50,000 new cases of cancer were being
reported each year.  VA has responded by developing a National Cancer
Strategy that expands on the already-existing relationship between VA
and NCI.  A key component of the strategy is an NCI-VA agreement,
similar to DOD's agreement with NCI, intended not only to increase
veteran access to cancer clinical trials, but also to expand
opportunities for clinician participation in trials.  The NCI-VA
agreement allows veterans to participate in a broad range of cancer
prevention, diagnosis, and treatment clinical trials. 

(See figure in printed edition.)Appendix III

--------------------
\23 Medicare also explicitly does pay for treating medical
complications that may result from patient participation in clinical
trials. 

COMMENTS FROM THE NATIONAL
INSTITUTES OF HEALTH
========================================================== Appendix II

(See figure in printed edition.)

(See figure in printed edition.)

(See figure in printed edition.)

*** End of document. ***