interpretation of epidemiological literature

8/8/2019 Interpretation of Epidemiological Literature

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Clinical medicine is continuously changing

and expanding, therefore physicians need todevelop methods of seeking out and applyingnew information

Clinicians must therefore develop skillsallowing them to update and reevaluate theirknowledge, enabling them to provide optimalpatient care


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A40-year-old accountant visited her family physician for a routinecheckup. The patients mother had been diagnosed with breastcancer in the past year, and the patient wanted advice about whatshe 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 normalPapanicolaou smear and mammogram. In responding to the patients questions about breast cancer, the

physician confirmed that a positive family history increases therisk of developing this disease. Anumber of other characteristicsare associated with a reduced risk of developing breast cancer,such as early age at first full-term pregnancy and increasing

number of pregnancies. The physician was also aware of acontroversy regarding the relationship between intake of dietaryfat and occurrence of breast cancer.


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Searching the literature Must locate appropriate literature

Reviewing the materialEstablishing causal relationship

Systematic review


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Helpful resources include: Computer technology because automatedx Medline: searches 4600 biomedical journals from 1966-

presentx Part of the National library of medicine

CD-ROMs

Printed books and journals

DVDs

The information is neither more nor less soundbecause of medium by which it happens to come toyou


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It is important to have a uniform and thoroughapproach to evaluate the articles

Steps: 1. Consider the research hypothesis 2. Consider the study design 3. Consider the outcome variable 4. Consider the predictor variables 5. Consider the method of analysis 6. Consider the possible sources of bias 7. Consider the interpretation of results 8. Consider the utility of the results All of these should be considered before passing

judgment on an article


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First a physician must determine the purpose of study and if it is clinically important There are various types of significance that may be ascribed to research findings

Is there a clear statement of the research hypothesis? Does the study address a question that has clinical relevance?

Type Meaning Assessment

Statistical Exclusion of chance as an explanation for

findings

Statistical tests

Clinical Importance of findings for change in current

clinical practice

Magnitude of clinical response to an

intervention

Biological Findings help to clarify the mechanism of

action

Compare findings of information from

invitro and invivo lab experimentation


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If the study question is of interest, the reader shouldthen determine what type of study design wasemployed:

Case-control, Cohort, or Descriptive

Depending on the disease the physician should determinewhich study design would be appropriate

Is the study design appropriate for the hypothesis? Does the design represent any advances over prior

approach? Does the study use an experimental or observational

design?


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Here one looks for the outcome of interest Looking at the patient profile the outcome of interest

is the development of breast cancer It is important to specify how the presence or

absence of breast cancer was determined Possibilities:

Death certificates limit information to deceased subjects.Information may be incomplete or inaccurate

Self-reports require that subjects be alive or have relatives thatcould provide information on breast cancer.

Medical records may provide more accurate information, butdiagnostic criteria may differ from physician to physician.

Histopathologic diagnosis It is important to judge how precisely the investigator

defines the outcome


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Is the outcome being studied relevant to

clinical practice?

What criteria are used to define the

presence of disease?

Is the determination of the presence orabsence of disease accurate?


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Risk factor or exposure under investigation More variables may limit the ability to collect

detailed info on exposure of interest (although it

may be more comprehensive) In a study of the cause of breast cancer, an investigatormay choose to examine a variety of exposure variables,including reproductive factors such as age at first full-term pregnancy, hormone levels, exposure to radiation,and dietary fat intake.

The reader must then determine whether themethods used to characterize the presence orabsence of exposure are reliable and accurate


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Methods Subject or surrogate respondent reports Direct observations Measurement of biomarkers

How many exposures or risk factors are beingstudied? How is the presence or absence of exposure

determined? Is the assessment of exposure likely to be precise

and accurate? Is there an attempt to quantify the amount or duration

of exposure? Are biological markers of exposure used in the

study?


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Types of bias

Bi Sourc of rror

Selection bias Sample distorted by selection process

Case-control studyHospital basedsample

Cohort studies

Information bias Misclassification of the variables

Systemic errors

Confounding An extraneous variable that accountsfor the observed result rather than the

risk factor of interest


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Number of

pregnancies

BreastcancerDietaryfat intake


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Is the method of selection of subjects likelyto have biased results?

Is the measurement of the exposure or thedisease likely to be biased?

Have the investigators considered whetherconfounders could account for the observed

results?

What direction would each potential biasinfluence the results?


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If the investigator reports a statistically significant result thatcant be explained by bias the reader must then decide

whether the result is clinically important. Ex:Astudy concluding that a 50% decrease in dietary fat

intake is associated with a 5% decrease in risk of

developing breast cancer. With statistics like this the patientmay not be motivated to make the dietary change.

How large is the observed effect? Is there evidence of a dose- response relationship? Are the effects biologically plausible?

If the findings are negative was there sufficient statisticalpower to detect an effect?


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The usefulness of a study finding depends onvarious factors, including the purpose of thestudy, the limitations of the study population, theclinical and biologic importance of the results,

and consistency with findings from otherpublished studies.

Are the findings consistent with other studies ofthe same questions?

Can the findings be generalized to other humanpopulations?

Do the findings warrant a change in currentclinical practice?


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Types ofstudy Applic tio to cli ic lpr ctices

Etiologic Can risk be reduced among

susceptible persons?

Diagnostic Can accuracy and timeliness of

diagnosis be improved?

Prognostic Can prognosis be determined more

definitively?

Therapeutic Can treatment be improved?


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Criteria for evaluating a suspected

causal relationship Strength

Presence of a dose-response relationship

Correct temporal sequence

Consistency of results across studies

Biological plausibility


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Strength of observed association Helps in determining whether a risk factor causes a

disease

Determined by the distance of risk ratio or oddsratio from the null value

Strong association is less likely due to chance or bias

Dose-response relationship An increase in the risk factor and an increase in

developing disease good association But this doesnt mean that the absence of a

progressive relation is bad association


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Low Moderate High Very high

Series 1

Series 1


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Temporal relationship Cause must always precede an affect in time

Sometimes suspected factors are actually the result of thedisease

x Ex:Aperson with an early undiagnosed cancer may make achange in food choices and then later they are diagnosed.

Case-control studies of chronic diseases with long latentperiods are particularly susceptible to this

Consistency Biological plausibility

The proposed causal relationship should be consistentwith what is currently known about biology and thedisease process


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meta-analysis is a type of quantitative systemicreview in which the results of multiple studiesthat are considered combinable are aggregated

together to obtain a precise, and hopefullyunbiased, estimate of the relationship in question Combines a series of smaller studies each with a

statistically imprecise estimate of effect, a larger samplesize is obtained, with corresponding increase in statisticalprecision

Identifies the differences in findings across differentstudies, sensitivity analyses can be conducted that maylead to greater insight into the sources of heterogeneity


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1.Formulate clear and meaningful question to beaddressed Things to consider:x Type of persons involved

x Type of exposurex Type of control with which the exposure is comparedx Outcome to be addressed

2. Search for studies of interest 3. extract the key data elements from the

included studies It is important when conducting meta-analysesthat selection of some studies and exclusions ofothers do not lead to a distorted conclusion


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In 2003 a meta-analyses of the

relationship between breast cancer and

dietary fat intake. The review included 45 studies (both case-control and cohort) with a combined total of

25,000 breast cancer patients and 580,000

control subjects. An overall small increase in

risk of breast cancer was associated with

elevated total fat intake in both case control

(OR=1.14) and cohort studies(RR=1.11)

interpretation of epidemiological literature

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