Pharmacy Law & Ethics

ETHICS & Medical Research

A case…
• Dr. R, a general practitioner in a small rural town, is approached by a
contract research organization (C.R.O.) to participate in a clinical trial of a
new non-steroidal anti inflammatory drug (NSAID) for osteoarthritis. She
is offered a sum of money for each patient that she enrolls in the trial. The
C.R.O. representative assures her that the trial has received all the
necessary approvals, including one from an ethics review committee. Dr. R
has never participated in a trial before and is pleased to have this
opportunity, especially with the extra money. She accepts without inquiring
further about the scientific or ethical aspects of the trial.
Importance of Medical Research

• medicine is inherently experimental”

• Medicine is not an exact science in the way that mathematics

and physics are. It does have many general principles that are
valid most of the time, but every patient is different and what
is an effective treatment for 90% of the population may not
work for the other 10%. Thus, medicine is inherently
experimental.
• All physicians make use of the results of medical research in
their clinical practice. To maintain their competence,
physicians must keep up with the current research in their area
of practice through Continuing Medical Education/ Continuing
Professional Development programs, medical journals and
interaction with knowledgeable colleagues. Even if they do not
engage in research themselves, physicians must know how to
interpret the results of research and apply them to their
patients.
Clinical Trial

• The most common method of research for practicing

physicians is the clinical trial. Before a new drug can be
approved by government mandated regulatory authorities, it
must undergo extensive testing for safety and efficacy. The
process begins with laboratory studies followed by testing on
animals. If this proves promising, the four steps, or phases, of
clinical research, are next:
Phase one

• Phase one research, usually conducted on a relatively small

number of healthy volunteers, who are often paid for their
participation, is intended to determine what dosage of the drug
is required to produce a response in the human body, how the
body processes the drug, and whether the drug produces toxic
or harmful effects.
Phase two

• Phase two research is conducted on a group of patients who

have the disease that the drug is intended to treat. Its goals are
to determine whether the drug has any beneficial effect on the
disease and has any harmful side effects.
Phase Three

• Phase three research is the clinical trial, in which the drug is

administered to a large number of patients and compared to
another drug, if there is one for the condition in question,
and/or to a placebo. Where possible, such trials are ‘double-
blinded’, i.e., neither research subjects nor their physicians
know who is receiving which drug or placebo.
Phase four

• Phase four research takes place after the drug is licensed and
marketed. For the first few years, a new drug is monitored for
side effects that did not show up in the earlier phases.
Additionally, the pharmaceutical company is usually interested
in how well the drug is being received by physicians who
prescribe it and patients who take it.
• The rapid increase in recent years in the number of ongoing
trials has required finding and enrolling ever-larger numbers of
patients to meet the statistical requirements of the trials. Those
in charge of the trials, whether independent physicians or
pharmaceutical companies, now rely on many other
physicians, often in different countries, to enroll patients as
research subjects.
• Although such participation in research is valuable experience for
physicians, there are potential problems that must be recognized and
avoided. In the first place, the physician’s role in the physician patient
relationship is different from the researcher’s role in the researcher research
subject relationship, even if the physician and the researcher are the same
person. The physician’s primary responsibility is the health and well-being
of the patient, whereas the researcher’s primary responsibility is the
generation of knowledge, which may or may not contribute to the research
subject’s health and wellbeing. Thus, there is a potential for conflict
between the two roles. When this occurs, the physician role must take
precedence over the researcher. What this means in practice will be evident
below.
• Another potential problem in combining these two roles is conflict
of interest. Medical research is a well-funded enterprise, and
physicians are sometimes offered considerable rewards for
participating. These can include cash payments for enrolling
research subjects, equipment such as computers to transmit the
research data, invitations to conferences to discuss the research
findings, and co-authorship of publications on the results of the
research. The physician’s interest in obtaining these benefits can
sometimes conflict with the duty to provide the patient with the best
available treatment. It can also conflict with the right of the patient
to receive all the necessary information to make a fully informed
decision whether or not to participate in a research study.
• These potential problems can be overcome. The ethical values
of the physician – compassion, competence, autonomy – apply
to the medical researcher as well. So there is no inherent
conflict between the two roles. As long as physicians
understand and follow the basic rules of research ethics, they
should have no difficulty participating in research as an
integral component of their clinical practice.
• The basic principles of research ethics are well established. It
was not always so, however. Many prominent medical
researchers in the 19th and 20th centuries conducted
experiments on patients without their consent and with little if
any concern for the patients’ well-being. Although there were
some statements of research ethics dating from the early 20th
century, they did not prevent physicians in Nazi Germany and
elsewhere from performing research on subjects that clearly
violated fundamental human rights.
• Following World War Two, some of these physicians were
tried and convicted by a special tribunal at Nuremberg,
Germany. The basis of the judgment is known as the
Nuremberg Code, which has served as one of the foundational
documents of modern research ethics. Among the ten
principles of this Code is the requirement of voluntary consent
if a patient is to serve as a research subject.
• The World Medical Association was established in 1947, the
same year that the Nuremberg Code was set forth. Conscious
of the violations of medical ethics before and during World
War Two, the founders of the WMA immediately took steps to
ensure that physicians would at least be aware of their ethical
obligations.

• In 1954, after several years of study, the WMA adopted a set

of Principles for Those in Research and Experimentation.
• This document was revised over the next ten years and eventually
was adopted as the Declaration of Helsinki (DoH) in 1964. It was
further revised in 1975, 1983, 1989, 1996, 2000 and 2008. The DoH
is a concise summary of research ethics. Other, much more detailed,
documents have been produced in recent years on research ethics in
general (e.g., Council for International Organizations of Medical
Sciences, International Ethical Guidelines for Biomedical Research
Involving Human Subjects, 1993, revised in 2002) and on specific
topics in research ethics (e.g., Nuffield Council on Bioethics [UK],
The Ethics of Research Related to Healthcare in Developing
Countries, 2002).
Declaration of Helsinki (DoH)
• Paragraph 15 of the DoH stipulates that every proposal for
medical research on human subjects must be reviewed and
approved by an independent ethics committee before it can
proceed. In order to obtain approval, researchers must explain
the purpose and methodology of the project; demonstrate how
research subjects will be recruited, how their consent will be
obtained and how their privacy will be protected; specify how
the project is being funded; and disclose any potential conflicts
of interest on the part of the researchers
DoH cont…
• Paragraph 12 of the DoH requires that medical research
involving human subjects must be justifiable on scientific
grounds. This requirement is meant to eliminate projects that
are unlikely to succeed, for example, because they are
methodologically inadequate, or that, even if successful, will
likely produce trivial results. If patients are being asked to
participate in a research project, even where risk of harm is
minimal there should be an expectation that important
scientific knowledge will be the result.
DoH cont…
• To ensure scientific merit, paragraph 12 requires that the project be
based on a thorough knowledge of the literature on the topic and on
previous laboratory and, where appropriate, animal research that
gives good reason to expect that the proposed intervention will be
efficacious in human beings. All research on animals must conform
to ethical guidelines that minimize the number of animals used and
prevent unnecessary pain. Paragraph 16 adds a further requirement –
that only scientifically qualified persons should conduct research on
human subjects. The ethics review committee needs to be convinced
that these conditions are fulfilled before it approves the project.
Social Value
• Paragraphs 17 and 21 of the DoH clearly favour the
consideration of social value in the evaluation of research
projects. The importance of the project’s objective, understood
as both scientific and social importance, should outweigh the
risks and burdens to research subjects. Furthermore, the
populations in which the research is carried out should benefit
from the results of the research. This is especially important in
countries where there is potential for unfair treatment of
research subjects who undergo the risks and discomfort of
research while the drugs developed as a result of the research
only benefit patients elsewhere.
Risks and Benefits
• “If the risk is entirely unknown, then the researcher should not
proceed with the project until some reliable data are available”
Risks and Benefits ….
• A risk is the potential for an adverse outcome (harm) to occur. It has
two components: (1) the likelihood of the occurrence of harm (from
highly unlikely to very likely), and (2) the severity of the harm
(from trivial to permanent severe disability or death). A highly
unlikely risk of a trivial harm would not be problematic for a good
research project. At the other end of the spectrum, a likely risk of a
serious harm would be unacceptable unless the project provided the
only hope of treatment for terminally ill research subjects. In
between these two extremes, paragraph 20 of the DoH requires
researchers to adequately assess the risks and be sure that they can
be managed.
Informed Consent
• The first principle of the Nuremberg Code reads as follows:
“The voluntary consent of the human subject is absolutely
essential.” The explanatory paragraph attached to this principle
requires, among other things, that the research subject “should
have sufficient knowledge and comprehension of the elements
of the subject matter involved as to enable him to make an
understanding and enlightened decision.”
Confidentiality
• As with patients in clinical care, research subjects have a right
to privacy with regard to their personal health information.
Unlike clinical care, however, research requires the disclosure
of personal health information to others, including the wider
scientific community and sometimes the general public.
Honest Reporting of Results
• It should not be necessary to require that research results be
reported accurately, but unfortunately there have been
numerous recent accounts of dishonest practices in the
publication of research results. Problems include plagiarism,
data fabrication, duplicate publication and ‘gift’ authorship.
Such practices may benefit the researcher, at least until they
are discovered, but they can cause great harm to patients, who
may be given incorrect treatments based on inaccurate or false
research reports, and to other researchers, who may waste
much time and resources trying to follow up the studies.
Conclusion…
• Despite all these potential problems, medical research is a
valuable and rewarding activity for physicians and medical
students as well as for the research subjects themselves.
Indeed, physicians and medical students should consider
serving as research subjects so that they can appreciate the
other side of the researcher-research subject relationship.
THANK YOU