The literature on a topic of clinical interest often includes
conflicting or inconclusive studies, thereby requiring the development
of critical skills for interpreting the results.
A systematic approach to evaluating the features of individual
studies can provide thoroughness and consistency to a review of
The evaluation of an individual study should include the research
hypothesis, the study design, the predictor and outcome variables,
the methods of analysis, possible sources of bias, and interpretation
In considering whether a statistical association is likely
to represent a causal relationship, one should consider the strength
of the association, the presence of a dose-response trend, correct
timing of events, consistency across studies, and biological plausibility.
A meta-analysis is a quantitative systematic review in which
the results of multiple studies are combined to obtain a precise,
and hopefully unbiased, estimate of the association under study.
A 40-year-old accountant visited her family physician for a routine
checkup. The patient’s mother had been diagnosed with breast
cancer in the past year, and the patient wanted advice about what she
could do to reduce her own risk of developing this disease. The
patient had two children aged 6 and 8 years. She was in good health,
with regular menstrual cycles, and she had a recent normal Papanicolaou
smear and mammogram.
In responding to the patient’s questions about breast
cancer, the physician confirmed that a positive family history increases
the risk of developing this disease. A number of other characteristics are
associated with a reduced risk of developing breast cancer, such
as early age at first full-term pregnancy and increasing number
of pregnancies. Unfortunately, these factors are not easily susceptible
to intervention, and the patient already had completed her childbearing.
The physician was also aware of a controversy regarding the relationship
between the intake of dietary fat and the occurrence of breast cancer.
Before recommending that the patient reduce her fat intake, however,
the physician wished to review the pertinent medical literature.
The recommendations that physicians make to patients depend on
the current state of knowledge available about diseases, the underlying
pathophysiology of diseases, and the most effective treatment for
diseases. The knowledge base of clinical medicine is continuously
expanding, and physicians must therefore develop methods to seek
out and apply new information.
This process is complicated when inconclusive or conflicting
results are found in the medical literature. The publication of
articles, even in the most respected journals, does not guarantee
that the investigators’ conclusions are valid, or even
if valid, relevant to the daily practice of a particular physician.
The history of medicine includes countless examples of therapies
that were once widely accepted but later were shown to be ineffective
or even harmful to patients. Clinicians must develop skills that
will allow them to update and reevaluate their knowledge, enabling
them to provide optimal patient care.
The first step in acquiring new medical knowledge is to ...