![](media/image1.png){width="1.5098425196850394in"
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height="1.3192913385826772in"}August 20, 2004

Division of Dockets Management

Food and Drug Administration

Via e-mail: <http://www.fda.gov/dockets/ecomments>

Docket #2004S-0233

The Blue Cross and Blue Shield Association (BCBSA) is pleased to respond
to the "Solicitation of Comments on Stimulating Innovation in Medical
Technologies" published in the Federal Register on May 24, 2004
(**Federal Register** Vol. 69, No. 100). BCBSA is an association of 41
independent Blue Cross and Blue Shield Plans ("Plans") providing health
benefits to almost 92 million members, one in three Americans. BCBSA
also provides scientific information on new technologies through BCBSA's
Technology Evaluation Center (TEC), jointly operated with Kaiser
Permanente. Technology assessments developed by TEC are available to all
users on the web at
[[http://www.bcbs.com/tec/index.html]{.underline}](http://www.bcbs.com/tec/index.html).
TEC is also an AHRQ Evidence-based Practice Center.

HHS has expressed the concern in the solicitation that "new discoveries
in basic sciences are not rapidly translating into new medical products
for patients." A statistic is cited indicating that only one in five
products that reach the clinical testing stage ever make it to
marketing. There are two processes that limit the transformation of
scientific discovery into clinical products that benefit patients. The
first is the transfer of basic research from the laboratory to product
development and testing in clinical trials. The second is the adoption
of the outcomes of clinical trials into mainstream clinical practice. A
key barrier to diffusion of effective new technologies is the dearth of
quality information that can be used by decision-makers- physicians,
payers, health plans, and consumers- "to make well-informed decisions
regarding alternative strategies for diagnosis and treatment of common
clinical conditions."[^1] We agree that "the current clinical research
enterprise in the United States is not consistently producing an
adequate supply of information to meet the needs" [^2] of
decision-makers.

BCBSA is not in a position to comment on the research and development
processes of private industry. It is clear, however, that truly
innovative devices or priority new molecular entities have comprised
only a small proportion of new products entering the FDA review cycle in
recent years. One study found that 50% of all new drug approvals in the
period 1995-2000 were for incrementally modified drugs while priority
new molecular entities accounted for only 13% of NDAs.[^3] Most new
devices reviewed by the FDA are cleared for marketing based on their
similarity, or substantial equivalence, to previously approved devices.
These devices are not viewed as significant innovations and the FDA does
not require evaluation of their clinical effectiveness.

In recent years, FDA has taken action to accelerate its review
processes. Speedier FDA approvals have been achieved by postponing the
collection and review of necessary data to the post-marketing period.
Regrettably, the promise of post-marketing studies has often failed to
produce good data on effectiveness necessary to determine the
appropriate use of new technologies. Reliance on post-marketing studies
or registries to fill in gaps in evidence has proven disappointing. In
most instances, the promised data have not been forthcoming. Carticel is
one example of this phenomenon. As a condition of Carticel\'s
accelerated Biologics License Application (BLA) approval, Genzyme was
required to conduct randomized trials to confirm clinical efficacy in
the post-marketing setting. These trials were never completed, and the
manufacturer claimed that patients were unwilling to enroll and
investigators were unwilling to participate. As a result, FDA revised
Carticel\'s label claim to second line use only, and this limited use
and coverage of the product in clinical practice.

In evaluating new technologies for coverage consideration, health plans
and employers seek evidence that the new technology improves clinical
outcomes for patients or will otherwise have a positive impact on
clinical management. Many of the new products in clinical testing may
fail to reach the market because they are not shown to improve health
outcome for patients. If such technologies do come to market, payers who
require evidence of clinical value in order to provide coverage will
deny coverage. What can the agencies of HHS, including AHRQ, do to
improve this situation?

-   The thresholds of evidence necessary to achieve FDA approval and
    coverage by Medicare should be defined clearly and communicated to
    developers of new technologies early in the development process.
    Clinical trials to demonstrate effectiveness should be designed to
    establish whether or not the evidence threshold is met. The evidence
    threshold for approval for marketing has not been the same as the
    threshold for coverage. The FDA seeks to determine that new drugs
    are safe and effective compared to placebo. Most devices are not
    required to demonstrate effectiveness at all. Payers must compare
    new technologies to alternative technologies and interventions. It
    is not in the interest of the beneficiary or society in general to
    have Medicare pay for technologies that are less effective than
    other products or modalities targeting the same clinical condition.
    Consideration should be given to raising the evidence threshold for
    FDA review.

-   Premature approval and diffusion of new technologies before clinical
    value is established can actually stifle meaningful innovation. An
    example from the last decade was high dose chemotherapy with
    autologous stem cell or bone marrow transplant support for breast
    cancer. Many oncologists promoted this technology as being a
    break-through for advanced and high risk disease. Had this treatment
    entered the mainstream as standard practice, thousands of women
    would have received a toxic therapy that was no more effective than
    conventional treatment with greater risk of side effects and death.
    Erroneous acceptance of this treatment as standard treatment would
    have reduced the impetus, and perhaps research funding, to discover
    alternate break-through treatment approaches that may improve length
    and quality of life.

-   Innovative break-through technologies must be evaluated in
    well-designed clinical trials that account for bias and that measure
    impact on the net health outcome. These trials can be costly to
    conduct. Contingent coverage for patient care costs in potentially
    definitive trials by Medicare may be appropriate in some instances.
    However, government support of the development and testing of new
    technologies should give government some voice in the ultimate
    marketing of the new technology. The phenomenon of huge price
    increases for drugs developed with government funding is troubling
    and should be addressed.

-   Nongovernmental stakeholders, such as private employers and health
    plans, can promote rational technology development and diffusion
    through a greater focus on evidence-based clinical utility.
    Equitable funding mechanisms for high priority trials of clinical
    effectiveness should be put in place.

BCBSA and member Plans recognize that continued innovation in medical
technology is essential if Americans are to continue having access to
the clinical breakthroughs they have come to expect. Government agencies
can play an important role in supporting innovation by clarifying
expectations for demonstration of effectiveness and clinical benefit and
by supporting the well-designed trials necessary to meet these
expectations.

Thank you for this opportunity to comment on this critical issue. If you
have any questions, please feel free to contact me at 312.297.6840.

![](media/image3.wmf)Sincerely,

Allan M. Korn, MD, FACP

Senior Vice President, Clinical Affairs and

Chief Medical Officer

[^1]: Sean R. Tunis, MD, et.al., "Practical Clinical Trials" JAMA,
    September 24, 2003, vol. 290, no.12, p. 1631.

[^2]: *[Ibid.,]{.underline}* p. 1625

[^3]: Michie Hunt.. Ph.D., "Changing Patterns of Pharmaceutical
    Innovation" NIHCM Foundation^?^