2010 How to critically read a medicine article

8/7/2019 2010 How to critically read a medicine article

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REBECCA J. BEYTH. MD, MSCNF/SGVHS GRECCUF COM DIVISION OF INTERNAL

MEDICINE

How to critically read anmedicine article


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IMRAD Format

y Introduction

Why the authors decided to do the study

y Methods

How they did it and analyzed their results

y Results

What they found

y

Discussion What the results mean


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Design: Randomized, parallel, placebo-controlled trial. Randomization

was computer-generated. Allocation wascentralized. Patients, caregivers, and outcome

assessors were blinded to group assignment.(ClinicalTrials.gov registration number: NCT00077753)

Hull RD et al. Ann Intern Med 2010;153:8-18.


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Critical Appraisal

When deciding if a paper is worth reading

y Check the design of the methods of section first!


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Question 1

y Why was the study done?

y What clinical question were the authors addressing?


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y The introductory sentence of a research papershould state in a nutshell what the background

to th

e research

isy Lets look at an example.


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Hospitalized medical patients have a high risk for

venous thromboembolism (VTE) (1). Recent studies(2 4) suggest that 5% to 15% of medical patients

who do not receive appropriate prophylaxis developobjectively confirmed deep venous thrombosis

(DVT). Up to 75% of fatal pulmonary embolismcases occur in hospitalized medical patients (5), and

VTE is associated with considerable long-termmorbidity and substantial consumption ofhospital

resources (6).

Introductory paragraph from: Hull RD et al. Ann Intern Med

2010;153:8-18.


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y This should be followed by a brief review of thepublished literature


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Large clinical trials have demonstrated the benefitsof short-term VTE prophylaxis in hospitalized

acutely ill medical patients; these benefits aremostly attributable to reductions in asymptomatic

VTE (2 4). On the basis of this evidence,guidelines recommend use of unfractionated

heparin, low-molecular-weight heparin, orfondaparinux for medical patients withheartfailure or severe respiratory disease or those whoare confined to bed with 1 or more risk factors,

such as cancer, previous VTE, or inflammatorybowel disease (1).

2nd paragraph from: Hull RD et al. Ann Intern Med 2010;153:8-

18.


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The studyhypothesis

y Should be clearly stated

In introduction or methods section

y If presented in the negative, it is known as null

hypothesis the addition of metformin to maximal dose sulfonylurea therapy

will not improve the control of type 2 diabetes


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The studyhypothesis

y Assume there is no difference, and try to disprove it

y Hypotheticodeductive approach Set up falsifiable hypotheses that you then proceed to test


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Extended-duration (4-week) prophylaxis has beenshown to significantly reduce the incidence of VTE

compared with a standard (1-week) regimen in high-risksurgical patients (710). However, studies have notassessed the efficacy and safety of extended-durationprophylaxis in acutely ill medical patients. Wehypot

hesized t

hat an extended-duration enoxaparinregimen similar to that evaluated in patients undergoing

elective hip arthroplasty (7) would be beneficial foracutely ill medical patients at high risk for VTE (11). Wedesigned a randomized clinical trial to assess the

efficacy and safety of extended-duration enoxaparincompared with placebo, following a 6- to 14-day,clinically proven regimen for VTE prophylaxis (2, 11).

3rd paragraph from: Hull RD et al. Ann Intern Med 2010;153:8-18.


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y Primary study

Reports research first hand

y Secondary (integrative) study

Summarize and draw conclusions from primary studies

Question 2: What type of study was done?


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y Parallel group comparison

Each group receives a different treatment

Both groups entered at the same time

Results analyzed comparing groups

Terminology


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y Paired (matched) comparison

Subjects receiving different treatments are matched to balanceconfounding variables (e.g., age, sex)

Results are analyzed in terms of differences between subjectpairs

Terminology


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y Within subject comparison

Subjects assessed before and after an intervention

Results are analyzed in terms of changes within the subjects

Terminology


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y Single blind

Either the subject, investigator, or assessor did not knowwhich treatment they were receiving

Side effects of th

e intervention or treatment may dictate th

e typeof blinding used

Terminology


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y Double blind

The subject, and investigator are unaware of the intervention

Terminology


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Design:Randomized, parallel, placebo-controlled trial.Randomization was computer-generated.Allocation was centralized.

Patients, caregivers, and outcome assessorswere blinded to group assignment.(ClinicalTrials.gov registration number:NCT00077753)

Hull RD et al. Ann Intern Med 2010;153:8-18.


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y Crossover

Each subject receives both intervention and control treatment(in random order)

Often separated by washout period with no treatment

Terminology


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y Placebo controlled

Control subjects receive a placebo (inactive pill) that look/tastethe same as active pill

Placebo (sham) surgeries also can be used

Terminology


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y Factorial design

Permits investigation of the effects (both separately andcombined) of more than one independent variable on a given

outcome 2 x 2 factorial design to test effects of placebo, aspirin alone,

TPAalone, or aspirin + TPA in acute MI

Terminology


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y Need to consider what broad field of research iscovered by the study

Question 3: Was the design appropriate to research?


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Design ResearchQuestion

Therapy:

y Testing the efficacy of drug treatment, surgicalprocedure, alternate methods of service delivery, orother interventions.

y Design: RCT


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Diagnosis:

y Demonstrate whether a new diagnostic test is valid(can we trust it), and reliable (would we get the same

results every time).y Design: Cross sectional survey where both new test

and gold standard are performed


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Screening:

y Demonstrate the value of tests that can be applied tolarge populations and that can pick up disease at a

pre-symptomatic stage

y Design: Cross sectional survey


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Prognosis:

y Determine what is likely to happen to someonewhose disease is picked up at an early stage

y Design: Longitudinal cohort study


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Causation:

y Determine whether a putative harmful agent isrelated to development of illness

y Design: Cohort or case-control study (depending onhow rare the disease is) case report may be helpful to provide crucial information


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Hierarchy of Evidence

1. Systemic reviews and meta-analyses2. Randomized controlled trials with definitive

results1. Confidence intervals that do not overlap the threshold

clinically significant effect3. Randomized controlled trials with non-definitive

results1. Point estimate suggests a clinically significant effect, but

with confidence intervals overlapping the threshold for

this effect


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Hierarchy of Evidence

4. Cohort studies

5. Case-control studies

6. Cross sectional surveys

7. Case reports


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y Is this study bigger, continued longer, or otherwisemore substantial than prior studies?

y Is the methodology more rigorous ?

Does it address methodological criticisms of prior studies?

Does this research add to existing knowledge?


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y Will the numerical results of this study addsignificantly to meta-analysis of prior studies?

Is the population that was studied different (e.g., ages, sex,or ethnic groups)?



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y Is the clinical issue addressed of sufficientimportance?

y Is there is sufficient doubt in minds of public or

key decision makers to make new evidencepolitically desirable, even when it is not strictlyscientifically necessary?



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y How were the subjects recruited? Any recruitment bias?

y Who was included in the study? Many studies exclude patients with co-existing

illnesses, non-English speakers, those taking certainmedications, illiterate, etc

May not necessarily apply to your patient population

Question 5: Whom is the study about?


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y Who was excluded from the study?

Maybe restricted to moderate or severe forms ofdisease

Lead to false conclusions about treatment aboutmild forms of disease

Results from trial ofhospital outpatients is used todictate best practices in primary care

Question 5: Whom is the study about?


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y Were the subjects studied in real-lifecircumstances?

Were they admitted purely for observation?

Were t

hey given very detailed instructions, or contactnumbers to call at any time

Did a company that fund the research provide newequipment that would not be available in ordinarypractice?

y These factors do not invalidate the study findings

but should give you pause on the applicability ofthe findings to your own practice

Question 5: Whom was the study about?


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What specific intervention was being used andwhat was it compared with?

Question 6: Was the design of the study sensible?


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Examples of problematic descriptions in methods

Author stated: We asked how often providers askpatients whether they smoke

y Assumes medical records are 100% accurate

Alternative: We reviewed medical records andcounted how manyhad their smoking status

recorded


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Examples of problematic descriptions in methods

Author stated: We randomized patients to withindividual care plan or usual care

y Failure to give sufficient information about theintervention

Alternative: The intervention group were offered

an individual care plan consisting of ., while thecontrol patients were offered


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What outcome was measured and how?

y Incurable disease measure efficacy of drug interms of whether it made you live longer, or

improved quality of life given your condition

y Less interested in the level of some obscureenzyme level as a surrogate endpoint


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y Look for evidence that the outcome measure wasobjectively validated

Confirmed that the scale of anxiety, pain, etc used in the

study measures what it purports to measure

Changes in this outcome measure adequately reflectchanges in the status of the patient


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Question 7: Was systematic bias avoided or minimized?

Systematic bias = anything that erroneouslyinfluences the conclusions about groups anddistorts comparisons

Regardless of study design, the groups comparedshould be as similar as possible except for theparticular difference that is being examined


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Reducing Systematic Bias

RCT

y Random allocation

Cohort studiesy Selection of the comparable control group is key

y Controlling is often done in analysis stage forbaseline difference in key variables


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Reducing Systematic Bias

Case-control studies

y Experiences of individuals with and withoutdisease are analyzed retrospectively to

identify putative agenty Most bias is the decision as to when the

individual became a case


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Question 9: Were the preliminary statistical questionsdealt with?

Three important numbers:

1. Sample size

2. Duration of follow-up

3. Completeness of follow-up


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Sample size

Trial should be large enough to have a highchance of detecting, as statistically significant, aneffect if it exists, and be reasonable sure that no

benefit exists if it is not found in the trial


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Sample size

What level of difference between the two groupswould constitute a clinically significant effect?

y May not be the same as statisticallysignificant

y Statistical nomograms to calculate how large asample needed for moderate, high, or veryhigh

chance of detecting true difference betweengroups (power)

80% - 90%


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Sample size

Underpowered study are quite common

y Harder to recruit subjects than anticipated

y Lead to type II or beta error

Erroneously conclude that an intervention has no effect

Type I or alpha error = erroneously conclude thatdifference is significant when it is due to sampling

error


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Completeness of follow-up

Withdrawals (drop outs)

y Less likely to have been adherent

y More likely to have experienced side effects

y More likely to have missed interim check ups


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Withdrawals

y Incorrect entry

y Suspected ADR

y Loss of patient motivation

y Clinical reasons (concurrent illness, pregnancy)

y Patient moves away

y Death


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2010 How to critically read a medicine article

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