CLINICAL DECISION IN HARM

CLINICAL SCENARIO You are the resident physician covering for the consultant in his clinic. You met
one of his patients, 45 year old male who is on anti-cholesterol medication. You
noted that his cholesterol is now only 4.35 mmol/l but the was still prescribed
with anti-cholesterol drug from his last week visit. You approach the consultant
and mentioned it to him. He told you it’s okay. It’s the high cholesterol that we
should be concerned with anyway.

Still doubtful, you went to the library and look for the harmful effect of very low
cholesterol level.

SEARCH You found the article by Zurek et al. entitled “ Serum cholesterol concentration
and death from suicide in men: Paris prospective study 1. Published in the
British Medical Journal, September 1996.

CRITICAL APPRAISAL

PRIMARY VALIDITY 1. Were there clearly identified comparison groups?

GUIDES just like studies of effectiveness of treatment, studies of harm require that a
control group for comparison should be done. Unfortunately, randomized
controlled trials to prove harm is not ethical, so studies of weaker design like
cohort or cross-sectional studies maybe relied upon. Both designs has a control
group for comparison. In the former controls are chosen by sequence of
exposure and in the latter by the absence of the outcome or disease.

In cohort study, a group of patients are observed. They are divided into those
with the exposure and those without the exposure. Then the outcome is
observed toward time.

In case-control study, patients with the outcome are gathered. Then the group
of patient without the outcome metched to the preceding group for certain
characteristics other than the exposure is also gathered. The presence of the
exposure in both groups is then ascertained.

In cross-sectional study, the patients are grouped and analyzed with respect to
their outcome and exposure. This study design can also be a basis for
establishing harmful effect but the temporal relationship of the exposure
occurring before the outcome can be established.

The study by Zurek observed6,728 men who had measurements of serum

cholesterol, They grouped and categorized cholesterol levels into low (>6.21).
The changes were also categorized. These were the comparison groups.

2. Were the exposures and outcomes measured in the same way in the groups
compared?

Measurement of outcomes must be similar in both groups in cohort study, the

investigators must show that diligent observation fot the outcome was done in
 the groups with the exposure (High risk) as well as the groups without the
exposure (low risk). When the patient with exposure were observed nore
diligently, there will be higher detection rate of the outcome leading to the
increase incidence of the disease in the exposed groups.. This is called
surveillance bias. This must be avoided. The bias may also occur in case-control
studies when the detection of exposure is more diligent in the group with the
disease or outcome.

Suicide data were taken from the national databases and death certificates in all
groups in the Zurek study.

3. Was follow-up sufficiently long and complete?

The length of follow-up must be sufficiently long enough to detect the outcome.
If follow-up is short, the chance of underestimating the effect of the exposure is
high. When the relation between asbestos and lung cancer was being
investigated the relative risk was only 1.4 in the early years of observation
compared to the subsequent relative risk of 18.2 when the years of
observations was extended to 15 years and beyond.

The Zurek study observed their patients for 4 years after enrolment. They had
95% follow-up.

SECONDARY VALIDITY 4. Is the temporal relationship between the exposure and outcome correct and
dose response gradient present?

GUIDES For an exposure to cause an effect, two important criteria maybe considered.
First the exposure must be present before the outcome and second there must
be a dose response gradient, i.e. the higher the dose the higher is the
probability of the outcome. Cross-sectional studies usually cannot establish
temporal relationship. Although, such design can establish a dose respons
gradient and a comparison between groups.

The Zurek study measured serum cholesterol before the event of suicide so the
temporal relationship was correct.

OVERALL< IS THE

STUDY VALID?

WHAT ARE THE 1. What is the magnitude of the association between exposure and outcome?
Was the estimate of the risk precise?

RESULTS? The relative risk is the incidence of the adverse effect in the group with the
exposure divided by the incidence of adverse effect in the group with the
exposure. If the relative risk is more than 1, then the exposure is causing harm.
Relative risk is usually computed when the design is a cohort study.

In a case control study, the odds ratio is computed. The odds ratio approximates
the relative risk especially when the risk is rare.
 The value of 95% confidence interval should be greater than 1 to say that the
exposure really causea harm. If one value of the 95% confidence interval is less
than 1 and the other is more than 1 and the other is more than 1, hten the
effect of exposure is uncertain.

The Zurek study showed that those with low cholesterol had increased risk of
suicide with a relative risk of 3.16 with a 95% confidence interval of 1.38to 7.22.
The analysis was also adjusted for age smoking and mean corpuscular volume.

CAN THE RESULTS HELP 1. Are the study patients similar to my own?

ME IN CARING FOR MY

PATIENTS? Just like in an article about a beneficial intervention, for the harmful effect to be
exploited to your patient you have to be assured that the characteristics of your
patient is similar to the study’s inclusion criteria.

The Zurek study recruited men between 43 to 52 years with similar

demographic characteristics with our patient.

2. Should I attempt to stop the exposures?

In answering this question you should consider the following:

1. How large and precise the risk of harm?

2. What are the consequences if I withdraw the exposure?
3. Do I have another alternative for the exposure?

Decision is simple when the answers to these questions are clear. For example
for cigarette smoking has been associated with increase incidence of lung cancer
and cardiac deaths, but withdrawing smoking may lead to “decreased quality of
life” for smokers. But recently an alternative like nicotine patch has been shown
to decrease withdrawal discomfort and eventually improve smoking cessation.
So the decision to withdraw for every patient consulting in the clinic is
warranted.

RESOLUTION OF THE Based on the appraisal you decided to go back to your consultant and inform

PROBLEM IN THE about the study that you found. He thanked you for the information and

SCENARIO and promised to withdraw the anti-cholesterol drug when the patient comes ba

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