Intervention trials in

medicine and public health

Nikolai Hristov, MD, PhD

Observations and interventions
• Epidemiological studies can be classified as either observational or
experimental.
• Observational studies allow nature to take its course: the investigator
measures but does not intervene. They include studies that can be
called descriptive or analytical:
• A descriptive study is limited to a description of the occurrence of a
disease in a population and is often the first step in an
epidemiological investigation.
• An analytical study goes further by analysing relationships between
health status and other variables.
Experimental studies
• Experimental or intervention studies involve an active attempt to change a
disease determinant – such as an exposure or a behaviour – or the progress
of a disease through treatment, and are similar in design to experiments in
other sciences.
• However, they are subject to extra constraints, since the health of the
people in the study group maybe at stake. Major experimental study designs
include the following:
• randomized controlled trials using patients as subjects (clinical trials),
• field trials in which the participants are healthy people, and
• community trials in which the participants are the communities themselves.
Experimental epidemiology
• Intervention or experimentation involves attempting to change a variable in one or
more groups of people.
• This could mean the elimination of a dietary factor thought to cause allergy, or testing
a new treatment on a selected group of patients.
• The effects of an intervention are measured by comparing the outcome in the
experimental group with that in a control group.
• Since the interventions are strictly determined by the study protocol, ethical
considerations are of paramount importance in the design of these studies.
• For example, no patient should be denied appropriate treatment as a result of
participation in an experiment, and the treatment being tested must be acceptable in
the light of current knowledge.
• Informed consent from study participants is required in almost all circumstances.
Randomized controlled trials
• A randomized controlled trial is an epidemiological experiment designed to
study the effects of a particular intervention, usually a treatment for a
specific disease (clinical trial).
• Subjects in the study population are randomly allocated to intervention and
control groups, and the results are assessed by comparing outcomes.
• To ensure that the groups being compared are equivalent, patients are
allocated to them randomly, i.e. by chance.
• If the initial selection and randomization is done properly, the control and
treatment groups will be comparable at the start of the investigation; any
differences between groups are chance occurrences unaffected by the
conscious or unconscious biases of the investigators.
Field trials
• Field trials, in contrast to clinical trials, involve people who are healthy but
presumed to be at risk; data collection takes place “in the field,” usually among
non-institutionalized people in the general population.
• Since the subjects are disease-free and the purpose is to prevent diseases that
may occur with relatively low frequency, field trials are often logistically
complicated and expensive endeavours.
• One of the largest field trials was that testing the Salk vaccine for the prevention
of poliomyelitis, which involved over one million children.
• Field trials can be used to evaluate interventions aimed at reducing exposure. For
instance, different protective methods for pesticide exposure have been tested in
this way and measurement of blood lead levels in children has shown the
protection provided by elimination of lead paint in the home environment.
Community trials
• In this form of experiment, the treatment groups are communities rather than
individuals. This is particularly appropriate for diseases that are influenced by
social conditions, and for which prevention efforts target group behaviour.
• The Stanford Five-City Project started in 1978 as one of several community
intervention studies designed to lower population risk of cardiovascular
disease. Researchers believed that the community approach was the best way
to address the large compounded risk of mild elevations of multiple risk factors
and the interrelation of several health behaviours.
• A community trial of a tuberculosis outreach programme in rural Ethiopia
encompassed 21 32 communities – with a combined population of 350 000
people, randomly allocated to intervention and control groups.
Behavioural interventions
• Such interventions include promoting tobacco cessation, increased physical
activity, dietary change and weight loss. Together, these may achieve a risk
reduction of over 60% in people with established heart disease, and
contribute to achieving good blood glucose control in people with diabetes.
• Doctors, dentists and other health workers are able to convince at least
some of their patients to stop smoking. A controlled trial of different anti-
smoking interventions in general practice showed that routine advice about
tobacco use is useful, and that its effectiveness can be improved with a
variety of techniques. In some countries, as many as 60% of current tobacco
users reported receiving advice to quit smoking from their doctors.
Pharmacological interventions
• For people with established cardiovascular disease, international
guidelines recommend long-term treatment of the risk of coagulation,
high blood pressure and high cholesterol. A combination of aspirin,
beta-blockers, angiotensin converting enzyme inhibitors and statins is
expected to reduce the risk of recurrent myocardial infarction by 75%.
However, there are large treatment gaps in all countries, in part because
of the cost and complexity of multiple drug use and other barriers to
affordable access.
• Clinical epidemiology has undoubtedly contributed to the improvement
of clinical practice. However, effective treatments are not fully used yet
and ineffective or costly and unnecessary treatments are widespread.
Other interventions
• Many other interventions are available for the management of high
risk patients and the treatment of established disease.
• These include environmental modification to reduce exposure to
allergies and other risk factors, stress management techniques,
counselling, and surgical interventions.
• There is much more that epidemiologists can do to improve clinical
practice.
Ethical issues
• Ethical issues are those involving actions and policies that are right or wrong, fair or
unfair, just or unjust.
• Ethical dilemmas arise frequently in the practice of epidemiology and ethical
principles govern the conduct of epidemiology, as they do all human activities.
• All epidemiological studies must be reviewed and approved by ethical review
committees.
• The ethical principles that apply to epidemiologic practice and research include:
• informed consent
• confidentiality
• respect for human rights
• scientific integrity
Informed consent
• Free and voluntary informed consent must be obtained from participants in
epidemiological studies and they must retain the right to withdraw at any
time.
• However, it may prove impracticable for informed consent to be given for
access to routine medical records. In such cases, as is the norm in any other
research study, epidemiologists must respect personal privacy and
confidentiality at all times. They have an obligation to tell communities what
they are doing and why, and to transmit the results of studies, and their
significance, to the communities involved.
• All proposals for epidemiological studies should be submitted to properly
constituted institutional ethics committees before the research work begins.
Confidentiality
• Epidemiologists also have an obligation to preserve confidentiality of
information they obtain through their studies.
• This also extends to the right of a person to withhold information
from others.
• As information in medical records, case registers, and other data files
and databases are generally confidential, epidemiologists are required
to obtain permission before being given access to these data.
Respect for individual rights
• Tension can often arise in epidemiological studies between the interests of the
group and the interests of the individual.
• An example is provided by efforts to limit the public health impact of HIV/AIDS.
Cuba successfully contained the spread of HIV/ AIDS by testing individuals at risk
and segregating infected people from the general population.
• Others argue that individual human rights are key to preventing infection
because spread of disease was facilitated by their denial; for example, women in
many affected countries cannot refuse demands for unprotected sex. In addition,
much of the behaviour that places individuals at risk of HIV/AIDS happens in
private, beyond the reach of the state. Public health efforts to modify the
behavior of vulnerable people are unlikely to be successful without assurances
that their interests will be protected.
Scientific integrity
• All scientists have the potential to behave in an unethical manner,
perhaps in part because of the pressure to succeed. Epidemiologists
are not immune to unethical behaviour.
• Examples include research results apparently influenced by conflict of
interests and the publication of fabricated data.
• Minimization of unethical behavior requires vigilance on the part of
ethical review committees and close attention to peer review of
publications. The training and mentoring of epidemiologists must
include serious and repeated discussion of these issues.