An Ethical
Debate: Financial ties as part of informed consent to
postmarketing research Attitudes of American doctors and
patient
John La Puma, Carol
B Stocking, director of research,a William
D Rhoades, attending geriatrician,b
Cheryl M Darling, clinical research
associate b
a
Center for Clinical Medical Ethics, University of Chicago,
Chicago IL 60637, USA john la puma, clinical associate
professor, b
Lutheran General Hospital, Park Ridge, IL 60068
Correspondence
to: Dr La Puma, 1945 North Burling Street, Suite 1R, Chicago,
IL 60614, USA.
Postmarketing
research, often called phase IV trials, is intended to
familiarise doctors and patients with newly approved drugs.
La Puma and colleagues, in Chicago, studied doctors' and
patients' attitudes to whether doctors should
receive payment for taking part in such research.
We asked for commentaries on their findings from
four ethical experts, who put the study in a British context,
present the views of patients, and examine some
methodological assumptions.
The attitudes of
doctors and patients about financial ties as part
of informed consent to research have not been studied. Neither
the United Kingdom's quadripartite regulations
nor new research guidelines in the United States
require financial disclosure to patients.
Postmarketing
(phase IV) research is part of the $10.9bn the American
pharmaceutical industry spends annually on research.Ordinarily uncontrolled observational cohort studies of
outpatients,
phase IV trials are often intended to familiarise
doctors and patients with new drugs approved by the
Food and Drug Administration. In the United States
phase IV trials and postmarketing surveillance (seeding
studies) are generally indistinguishable.
Industry sponsors
pay doctors to enrol their patients and to collect
dosage and effect information. Patients may receive the
new drugs free; doctors may also receive payment for
laboratory examinations and office visits. Yet
patients may be unaware of their status as research
subjects.
Methods
To understand
patients' and doctors' attitudes about these arrangements,
we developed structured, parallel, self administered
questionnaires to gather data on attitudes about
informed consent to, financial disclosure about,
and participation in postmarketing research. The
questionnaire for doctors was pretested and validated and
then distributed to all active staff physicians (n=733)
of a large, suburban, community teaching hospital.
The questionnaire
for patients was pretested and validated, and then
distributed by a research associate to consecutive patients
(n=269) in a general medical office. Patients under 18
years of age and those who seemed to be acutely ill were excluded
(n=29).
Participation was
voluntary and confidentiality was assured. The
institutional review board of Lutheran General Hospital approved
the research protocol.
Results
Of the 733 doctors
surveyed, 394 (54%) responded. Age in years (mean
45.4 (SD 11.5)) and sex distribution (79% (297) male) of
respondents did not differ from that of the staff as a whole.
Respondents had been in practice for 1-60 years (mean
14.6 (11.1)) and represented all clinical
departments.
Of the 269
outpatients approached, 200 (74%) returned completed surveys.
Respondents ranged in age from 18 to 87 years (mean 49.7
(16.9)). Most were female (64%; 123), in excellent or very
good health (53%; 103), and had a regular doctor (85%;
167). Twelve (6%) had been part of a research study
on a new drug.
One hundred and
forty four doctors (36%) had been asked by a drug
company to enrol patients in a phase IV trial. Of the 106
(27%) who had participated, 79 reported whether and how
much they had received for each patient enrolled.
Forty one of 79 (52%) reported that they had not
been paid a fee; three wrote in the margin that a
programme, institution, or employer had accepted
the fee for them. Thirty eight reported that they had been
paid from $5 to $5000 (median $80) for each patient enrolled.
Most doctors (64%;
240) found it acceptable to be paid a fee, while
most patients (56%; 110) found a fee unacceptable
(P<0.005). Proportionately fewer doctors (75%;
282) than patients (86%; 171) believed that a
physician should inform a patient if the physician
is paid for enrolling the patient (P<0.005) (table).
Responses to questions about investigators' financial ties to research
sponsors
---------------------------------------------------------------------------
%(No) responding "yes"
or "probably yes"*
---------------------------------------------------------------------------
Patients Physicians
(n=200) (n=394)
---------------------------------------------------------------------------
When a doctor asks a patient to participate in a
research study, should he/she tell the patient:
What company, agency, or foundation is
paying for the study? 92 (183) 85 (328)
Whether he or she owns stock in the
sponsoring company? 78 (155) 74 (277)
Whether he or she is paid a salary by
the sponsoring company? 81 (159) 78 (295)
Whether he or she is paid a fee for each
patient enrolled? 86 (171) 75 (282)+
---------------------------------------------------------------------------
*Some subjects did not respond to all questions. +P < 0.005.
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Respondents who
found fees acceptable were asked how much, over the
direct costs, the doctor should be paid to enrol each patient.
Ninety five doctors made this estimate, most frequently
suggesting $100 (range $10-$2500, median $100).
Patients who made this estimate (n=31) answered $10
most frequently (range $10-$100, median $15).
Most responding
doctors (67%; 253) and patients (69%; 133) thought that
some doctors might be influenced to enrol patients just for
the fee.
Discussion
Moral questions of
dual loyalty, research purpose, truth telling, and
informed consent for phase IV investigators raised by these
data have been explored briefly elsewhere.5
6
We know of no data which suggest that doctors
actually include their remuneration for research as
part of the informed consent process. Indeed, doctors
who inform patients may encounter resistance to enrolment.
Conclusion
Doctors and
patients disagree about whether remuneration of doctors
is acceptable in phase IV research but agree that information
about financial ties to the research sponsor should be
part of informed consent. Such information would
make explicit a part of the conflict of interest
that confronts doctors who are simultaneously
clinicians and phase IV investigators receiving enrolment
fees. Whether disclosure is enough to extinguish doctors'
conflict of interest in post-marketing research provides
opportunity for further study.
These data were
presented at the 16th annual Society for General Internal
Medicine national meeting in Washington, DC, 1993; the
7th annual Society for Medical Decision Making national meeting
in Triangle Park, North Carolina, 1993; and the 5th annual
University of Chicago McClean conference in clinical medical
ethics in Chicago, Illinois, 1994. The work was funded in
part by the Lutheran General Hospital and the Lutheran General
Medical Group. The views expressed in this paper are
those of the authors and do not necessarily reflect
the views of the supporting institutions.
- Joint Committee of the ABPI,
BMA, CSM, and RCGP. Guidelines on postmarketing
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- Public Health Service, US
Department of Health and Human Services. Notice of
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- Ray WA, Griffin MR, Avorn J.
Evaluating drugs after their approval for clinical use. N
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- Stephens MDB. Marketing
aspects of company-sponsored postmarketing surveillance
studies. Drug Safety 1993;8(10):1-8.
- La Puma J, Kraut J. How much
do you get paid if I volunteer? Suggested institutional
policy on reward, consent, and research. Hosp Health
Serv Admin 1994;39:193-203.
- La Puma J. Physician rewards
for postmarketing surveillance (seeding studies) in the
US. Pharmacoeconomics 1995;7(3):187-90.
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