By Charles A. Schiffer, MD
2008-03-01
Dr. Schiffer is Professor of Medicine and Oncology at the
Karmanos Cancer Institute, Wayne State University School of Medicine.
In what in retrospect seems historically quaint, when I graduated
from medical school in the late 60s, there were major disagreements
among class members about the appropriateness of accepting stethoscopes
and doctors' bags from pharmaceutical companies. Shortly thereafter,
during my initial years in oncology, there were relatively few drugs,
little attention to where they came from, and virtually no interactions
with drug companies and their representatives.
Contrast this with the current situation in which private
practitioners and academic physicians are inundated with contacts from
pharmaceutical representatives in their offices, at
educational/promotional dinners and trips, at company supported "in
service" lectures for the doctors' staff (often with the company
representative as the speaker), at lunch conferences at community and
university hospitals, at regional or national "consulting" meetings
coordinated by marketing groups, and at the annual meetings of their
research societies. In exchange for a free lunch or fine dinner,
companies are able to promote their products to physicians and staff,
gather information about the usage of competitors' products as well as
gather some information about patient volumes and demographics, and
generate good will. Indeed, current trainees and junior physicians have
been "raised" in this environment and consider this business as usual.
Although physicians are wont to maintain that they are "above" such
influences, the multi-million-dollar marketing investment by
pharmaceutical companies, which in turn is incorporated into the cost
of drugs, is based on data which strongly support the effectiveness of
such approaches.
Interdependence has developed between the pharmaceutical industry
and all levels of hematologic/oncologic activities, including those of
the academic societies. The latter benefit from the revenue derived
from journal advertising, the acres of exhibits at the national
meetings, the fees for "Super Friday" corporate-sponsored symposia, and
grants in support of travel and fellowship awards, as well as the
considerable boost in meeting registrations provided by corporate
support of travel and expenses for participants from overseas. ASH and
ASCO are scrupulous in their review of these contacts, with guidelines
assuring independence in the use of these funds, but the potential for
"gray" areas abound.
Pharmaceutical-Company-Sponsored Clinical Research
In addition to these concerns related to clinical practice, and of
particular relevance to research societies and academic centers, are
issues arising during the conduct of pharmaceutical-company-sponsored
clinical trials. Because pharmaceutical companies are the major source
of novel and interesting therapeutic compounds, it is of critical
importance to efficiently and collegially conduct pre-clinical and
clinical research in collaboration with these companies.
Drug-company-sponsored trials have become a key source of clinical
research submissions to the ASH and ASCO annual meetings. For example,
I analyzed that approximately a third of the oral presentations in the
hematologic malignancies sessions at ASH's annual meeting in 2006 were
sponsored by a pharmaceutical company or had co-authors from companies.
Similarly, 44 percent of 332 clinical trials published in the Journal of Clinical Oncology in 2005 reported funding by pharmaceutical companies.1
A number of issues can complicate these collaborations:
- It can be difficult to distinguish the
presentation of new information at the annual meeting from marketing.
It is common to see multiple presentations from the same company
rehashing or "updating" older data, frequently focusing on subgroup or
interim analyses, often with essentially the same information presented
at ASCO the following spring. Judging by the similarities in format,
these are often (usually?) prepared by the company, and, not
infrequently, the abstracts/slides/posters are sent to the authors with
short notice without the opportunity to review the primary data or have
substantive input into the content. At the other end of the spectrum
are submissions containing data that are too preliminary for meaningful
interpretation, and company executives have acknowledged to me that
such presentations are sometimes aimed more at investors than the
scientific audience.
- Abstracts/manuscripts
are often written by investigators from companies or by writers hired
by the companies, a point which is sometimes, but not usually,
acknowledged in the publication. Although this is not necessarily
"bad," the authors of the abstract/paper have the critical
responsibility for careful review of the data and the language used to
describe the conclusions, particularly given the recent report that
evaluated articles published in the Journal of Clinical Oncology
and concluded that "conflicts of interest are associated with highly
positive conclusions that use superlatives to promote the experimental
arm."2 It has been suggested that investigators and
companies adhere to recently proposed AAMC Guidelines for Protecting
Integrity in the Conduct and Reporting of Clinical Trials to help
provide consistency and transparency in the conduct and reporting of
such trials.
- There has been considerable
interest in the lay press and academic journals about the effects of
financial conflicts of interest (COI) posed by consultancies and stock
ownership, with some articles documenting excessive honoraria to
physicians for unbalanced presentations of clinical data. Of perhaps
greater importance than what hopefully represents outliers, are other
more subtle influences, including the potential effect on investigator
objectivity of a career-advancing association with "positive" studies.
This can result in the traditional rewards of publication, academic
promotion, subsequent grant funding, and the ability to direct/attract
the next major trial to one's institution, but it can also provide
opportunities for remunerative consulting and extensive travel for
lectures at restaurants and other non-academic venues around the
country, often using slides prepared by the burgeoning industry of
medical education companies. Few can claim indifference to these side
benefits, although the temptations might be less if younger academics
were paid more competitive wages. Professional societies, regulatory
agencies, and universities have guidelines governing these interactions
in place, although it remains unclear whether these are really
realistic and functional and capture the impact (if indeed there is an
impact) of these less obvious COI.
- There
are also issues about interactions with clinical research
organizations, including the emphasis on the excessive amount of data
collected on industry-sponsored trials and the large number of
frequently meaningless data queries, which decrease the efficiency of
the conduct of trials, consume the time of data managers, and, thereby,
reduce the number of trials that institutions can open. This is an area
requiring more attention and new methodological research focused on
whether data minimization might be sufficient for most clinical trials.
Conclusion
It is always easier to harp on the more negative and polarizing
aspects of contentious issues such as this. However, pharmaceutical
companies have and will continue to contribute enormously to the
improved care of our patients, and these interactions are therefore
likely to increase. Whatever new regulations may be forthcoming, in the
end, the ultimate responsibility will reside with the individual
physician and investigator who will, at times, have to react to some of
the situations described above. Most will continue to respond with
intelligence and integrity, although certainly they should maintain a
questioning and critical attitude about these relationships.
Dr. Schiffer consults for Novartis, Celgene, Roche, Amgen, and
Pharmion and receives research funding from Novartis, Bristol-Myers
Squibb, and Celgene. He participates in speakers' bureaus for Novartis,
Celgene, and MGI Pharma and is a member of scientific advisory
committees for Kanisa and Celgene.
- Riechelmann RP, Wang L, O'Carroll A, et al. Disclosure of conflicts of interest by authors of clinical trials and editorials in oncology. J Clin Oncol. 2007;29:4642-7.
- Riechelmann RP, Dounaevskaia V, Taback
N, et al. Source of funding, conflict of interest (COI), and the
interpretation of cancer clinical trials. Proc ASCO. 2007;25:6530.
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