Clinical Research
Thomas R. Lunsford, MSE, CO
ABSTRACT
This article is a discussion of the basic
concepts and categories of clinical research. Because the current state-of-the-art in research is the result of more than
200 years of developments, the essential
elements such as interventions, control
groups, randomization, blindness, placebo, the Hawthorne effect and informed consent are reviewed.
Introduction
Clinical research for the orthotist and
prosthetist means a systematic process
for formulating and answering questions about the uses of, basis for, and
effectiveness of orthoses and prostheses. The need for research to develop
O&P management as a science and an
art has been documented (1-5). The
American Academy of Orthotists and
Prosthetists (AAOP) at both national
and local levels, as well as the editorial
board of JPO, recognize the need for
research to advance the O&P profession and industry.
One has only to attend either of the
annual meetings to verify the paucity of
research. Similar results would occur
from reviewing past issues of JPO (aka
CPO and Orthotics and Prosthetics).
The JPO editorial board has developed
specific goals and an overall plan to
assist practitioners in conducting research.
Reimbursement and funding agencies are beginning to demand validating research for the techniques and devices associated with O&P. As new and
improved devices emerge from higher
technology, clinical research must be
conducted to validate their effectiveness
and help justify their reimbursement.
Also, new ideas and devices should
be subjected to rigorous clinical research as a prerequisite to endorsement by NCOPE, our educational credentialing organization. Moreover,
curricula at our educational institutions
should identify devices proven effective through clinical trials, those that
show promise or are widely advertised,
and those that have no impartial evidence to demonstrate their efficacy.
It is imperative that the O&P profession and industry develop and implement clinical assessments, as well as
instruments, that are bias-free and capable of providing quantifiable measures of patient (consumer) benefits derived from use of the devices provided.
Patient assessment and devices must be
valid, reliable and have demonstrable
effectiveness.
Research Skills
You probably have latent research
skills if you find yourself not accepting
what people say or write. Ask yourself,
or others, or the literature, is this really
so? This is an attitude practitioners
must cultivate to perform critical assessment. A researcher must have an
inquiring mind and a skeptical outlook.
Enthusiasm is also a requisite, but it
must be tempered by a capacity for sustained concentration and a complete
lack of bias. It is not easy to be cool and
objective when continually working
under pressure in a busy environment.
However, if the results of your observations are to have any value, they
must be untainted by any bias.
Some confuse research with development or engineering. Many practitioners
are crafty and like to tinker, and, in
much the same manner as an engineer,
design new and improved devices, components and processes. Developing a
"better mouse trap" requires a keen
clinical sense and a bent for creativity.
Sometimes a new device is developed
not necessarily to improve function, but
to reduce cost or enhance durability, etc.
There is a certain freedom to this process, and few rules apply.
Research, however, is more structured, more disciplined and has many
rules. Research may involve evaluating
or comparing a new orthosis or prosthesis to conventional devices. Moreover, the developer of a device is not
considered to be an impartial judge of
the performance or comparison of the
new device.
Students frequently claim they are
going to the library "to do research."
Although a review of pertinent literature is an important phase of research,
the process of reviewing literature is
not, in itself, research. The word
"search" is a more appropriate term to
describe reviewing literature.
Clinical Investigation
Every practitioner who performs a
clinical investigation, such as an analysis of patients treated with a specific
device, or a trial on the treatment of a
painful or unstable knee with knee
orthoses, will be contributing to the
sum of knowledge in our profession,
which is the aim of all research. For
example, to improve or validate your
clinical knowledge, you might need to
know why patients with a given disease
or in a condition category respond well
to a certain orthosis or prosthesis while
others whose conditions are apparently
comparable do not improve using the
same device.
If O&P is to remain independent,
and at the same time grow and improve, an understanding and appreciation of the role of clinical research is
necessary. All practitioners should
make some contribution to the scientific validation of their practice, and
that means discovering and validating
the concepts and principles on which
O&P devices are based.
The research mentality (it is as much
a state of mind as it is a process) should
be a working tool for the practitioner.
In the words of Pruden, "We need to
strip research of its aura of glamour or
mystery, to reduce it to a size that fits
our laboratory workbench and to make
it a realistic part of each of our daily
activities (6)."
If we as orthotists and prosthetists
are not motivated to do our own re-
search, others will do it for us. Those
others will gain knowledge, and eventually our identity as a unique profession will be lost.
Defining "Research"
If you were to examine textbooks on
research, you would discover there is
no single, agreed-upon definition of
what is meant by the term research.
Some authors define research in a restricted sense, involving scientists in a
laboratory who manipulate variables to
study the effect on other variables.
Other authors state that practically
anything done to discover knowledge
qualifies as research.
While the definitions of research differ considerably, similar elements typically appear. To have a common frame
of reference about the concept of research, the following definition, which
summarizes and integrates these similar elements, has been proposed: Research is a way of discovering knowledge through the systematic investigation of a problem (1).
Some of the implications of this definition are (a) research is a way and not
the only way to discover knowledge,
(b) research is a systematic process,
and (c) research is problem-oriented.
Clinical research in O&P is important
in validating clinical practice, and all
research eventually leads to the central
question: What difference does it make
to the patient?
Classification
A popular classification of research
that has some degree of acceptance distinguishes basic, or pure research, from
applied research. Basic research tends
to be abstract and general and is conducted either to generate new theories
or to gain knowledge or understanding.
The results of basic research may
have some practical usefulness, but the
researcher does not start with a specific
application in mind, e.g., examining a
new molecule or compound that may
eventually form a new fabrication material. Conversely, applied research is
conducted so that a device or technique
can be improved or to answer specific
questions.
The researcher has a particular application in mind when designing the
study. The O&P practitioner has, as a
rich source of research topics, many
questions about devices, processes and
ways to help human beings live useful,
productive lives. O&P practitioners
tend to be interested in practical, applied matters.
Research is sometimes classified according to where it is conducted, such
as clinical research or laboratory research, or by the area in which it is
conducted, such as educational research or administrative research. Perhaps a more useful classification is by
differences in the actual method used
in the research process.
A common distinction is between experimental and descriptive research.
Experimental research is characterized
by the manipulation of a variable (the
independent variable) to study its affect on another variable (the dependent variable). It is the approach used
when the researcher wishes to examine
cause-and-effect relationship and is
prospective. Descriptive research is the
method used when the purpose of the
study is to describe a situation, a group,
an individual or other phenomena. Descriptive research includes surveys,
correlational studies, trend analyses,
developmental studies and methodological studies and is often retrospective.
A retrospective study is a review of
cases from the past (7). The study is
conceived after patients have been
treated. Typically, one searches the
medical charts to identify a series of
patients in which one is interested.
Their charts are pulled, and relevant
data are collected and analyzed.
A prospective study is conceived before patients are treated. The hypotheses and experimental design are determined before the onset of the study.
Protocols are written and forms are
used to ensure all relevant data are collected. A randomization process may
be devised for enrolling patients into
either the experimental or control
group. The study is carried out either
for a specified time or until a specified
number of patients is enrolled.
In principle, a retrospective study
may be just as good as a prospective
one, provided record keeping has been
thorough. In practice, retrospective
studies are plagued by missing data and
poor control. Some patients are not
identified, key points are not recorded
in the charts, and timing and records of
follow-up visits are haphazard. The
identification of a suitable control
group is often impossible. There is no
way to assess bias or inconsistency in
data collection. All of these factors impart a shakiness to retrospective studies. Realistically, there is very little
control.
Evolution of Research
The evolution of clinical research (clinical trials if it involves patients) dates
back to the 18th century and includes
several important concepts, e.g., intervention, control groups, randomization, blindness, placebo, Hawthorne
effect and informed consent (8,9).
Intervention
Clinical research employs one or more
intervention techniques. An intervention technique in O&P might be the
evaluation of a new socket or ankle-foot orthosis thought to be more effective. The intervention device should be
applied to subjects in a standard fashion in an effort to change a therapeutic
or functional aspect (e.g., walking,
strengthening, range of motion, vocational goal, etc.) of the subject.
Follow-up of subjects who have been
trying a new device over a period of
time may measure the natural history
of a disability, but it does not constitute
a clinical trial. Clinical research requires active intervention and a real
time evaluation of the prospective device. Without active interventions the
study is observational or retrospective
because no experiment is being performed. Intervention may be thought
of as a new prosthetic foot or AK socket or a new knee or cervical orthosis.
Control Groups
Clinical research must contain a control group against which the intervention group is compared. The control
group must be sufficiently similar to
the intervention group that outcome
differences may reasonably be attributed to the intervention. Most often a
device (intervention) is compared with
the best current alternative. If no such
standard exists, the subjects in the
new- or test-device group may be compared to subjects who have no device
during the test or measurement period.
Randomization
In the simplest case, randomization is a
process by which each subject has the
same chance of being assigned to any
one of the devices being compared or
to the control device. An example
would be the toss of a coin, in which
heads indicates the testing of the intervention group of devices, and tails indicates the control device group or no
device.
Even in the more complex randomization strategies, the element of
chance underlies the allocation process. Of course, neither subject nor investigator should know what the assignment will be before the subject's
decision to enter the study. Otherwise,
the benefits of randomization can be
lost.
Blindness
Bias is one of the main concerns in clinical research. Bias has been defined as
"systematic error or difference between the true value and that actually
obtained due to all causes other than
sampling variability"(1O). Bias can be
caused by conscious factors, subconscious factors, or both. Bias can occur
at a number of stages during clinical
research, from the initial design
through data analysis and interpretation.
The general solution to the problem
of bias is to keep the subject and the
investigator blinded to the identity of
the device (or intervention) being evaluated. Obvious bias exists when the developer or designer of a new or innovative device is involved in its evaluation.
Evaluation by a second or third party is
necessary to preserve the designer' s integrity.
Placebo
A special kind of intervention (treatment or device) used in some experiments is the placebo. The subjects
think they are receiving an experimental device when in reality they are not.
In a study where control subjects are
identified but not aware they are being
used as controls, while experimental
subjects are well aware they are participating in a study, scores (outcome) for
the experimental group might be higher solely as a result of the subjects'
knowing they are involved with the improved design or higher technology.
Interest or motivation may alter the
behavior of the experimental group.
Including a group using placebo devices that is told it is using the new or
high technology device will identify
whether this knowledge is responsible
for enhanced performance.
In traditional pharmaceutical research the placebo is an inactive substance usually shaped and colored to
look like the active drug. The placebo
is given to a control group to test the
therapeutic effects of the active drug.
The patients (subjects) never know
which drug they are getting. This may
be difficult in O&P since many patients
are very sophisticated and will be able
to identify which of the devices being
evaluated is the new or intervention
device. Two researchers. Benson and
Epstein, have shown that the placebo
alone can produce beneficial therapeutic effects (11).
Hawthorne Effect
A concept distinct from placebo is the
Hawthorne effect. This phenomenon
was discovered between 1927-1932 by
Elton Mayo and a group from Harvard
University at the Hawthorne facility of
Western Electric Co. (12). These researchers originally set out to determine the effect of lighting on fatigue
and efficiency in factory workers.
The researchers discovered that no
matter what they did to the lighting,
production improved, and the factory
workers reported less fatigue. Obviously, Mayo learned very little about
lighting variables and fatigue, but discovered an important phenomenon.
He discovered knowing they were participating in an experiment significantly changed the workers' perceptions of
their job situations and improved their
productivity. This study demonstrated
the beneficial effects of being made to
feel important and different in an otherwise dull work setting.
Clearly, the Hawthorne effect could
operate in a clinical research study. If
the subjects know they are participating in a research study, they may be
motivated to perform better. Legally
required informed consent forms promote the Hawthorne effect. Therefore,
the clinical researcher must be aware
that the Hawthorne effect, like the placebo, may be the reason a new knee
orthosis or prosthetic foot, for example, produces significantly improved
function.
Informed Consent
To assure compliance with the principle of informed consent, most states
have health and safety codes that require investigators to inform people
participating in medical research of
their rights by providing each subject
with a written copy of the "Rights of
Human Subjects in Medical Experiments" (13). Informed consent documents generally consist of two parts: 1)
"Rights of Human Subjects in Medical
Experiments" and 2) a written consent
form, specific to the study being conducted, which describes in layman's
terms each of the topics covered in the
"Rights of Human Subjects in Medical
Experiments."
A truly informed subject is likely to
be a better complier. Therefore, for
scientific as well as ethical concerns,
the subject (or guardian) in any clinical
research should be clearly instructed
about the study and told what is expected.
Sufficient time should be spent with
subjects to ensure they understand the
specific objectives of the study and the
impact they will have upon the results.
Subjects should be encouraged to consult with their families or physicians before participating. A question-and-answer sheet concerning the study is
often helpful.
Most hospitals, all federal agencies
providing grant support, and any other
group serving in a consulting or controlling capacity over research projects
require compliance with the recommendations of the World Medical Association regarding medical research.
This document, originally entitled
"Declaration of Helsinki," was adopted in 1961 and later revised at the 19th
World Medical Assembly in Tokyo in
1975 (13).
In January 1981, the Department of
Health and Human Services and the
Food and Drug Administration published in the Federal Register final regulations amending the basic policies for
the protection of human subjects in research (13-15). The regulations, effective July 27, 1981, apply to research
funded by those agencies.
Conclusion
Participating in clinical research will
make you a better O&P practitioner.
Clinical research provides you with
knowledge that distinguishes you from
unqualified individuals who wish to
practice your craft. You may have
heard that research enhances the stature of health professionals. Indeed, the
most respected professions have a
strong and growing research base. D
Thomas R. Lunsford, MSE, CO, is director of the orthotic department at The Institute for Rehabilitation Research in Houston. He also is president of the Academy.
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