Copyright H Photography 2006 iStockphoto.com Pragmatic cohort studies and comparative effectiveness...

Copyright H Photography 2006 iStockphoto.com

Pragmatic cohort studies and comparative effectiveness

Eric S Johnson, PhDKaiser Permanente’sCenter for Effectiveness and Safety Research

AHRQ’s Effective Healthcare Program:Scientific Resource Center

June 18, 2010 UC Davis School of Medicine

http://www.itv.com/Drama/family/JeevesandWooster/picturegallery.html

Copyright Matt Knannlein 2005 iStockPhoto.com

The risk of death associated with the use of conventional versus atypical antipsychoticsamong elderly patients

Sebastian Schneeweiss, Soko Setoguchi, Alan Brookhart, Colin Dormuth, Philip S Wang

Canadian Medical Association Journal 2007;176:627-32


BMJ’s PICO format: Study question

Do conventional antipsychotic drugs pose risks equal to orgreater than those associated with newer, atypical drugsin an elderly population?


BMJ’s PICO format: Design, intervention and control

We conducted a retrospective cohort study of elderly patients with a diagnosis of dementia who started a conventional or an atypical antipsychotic drug.


BMJ’s PICO format: Participants and setting

We followed 37,241 patients 65 years or older who started an antipsychotic drug between 1996 and 2004 and wereresidents of British Columbia.


BMJ’s PICO format: Outcomes and their timing

We compared the 180-day all-cause mortality rate for patientswho started conventional versus atypical antipsychotic drugs.


BMJ’s PICO format: Results and role of chance

Of the 24,359 (control cohort) patients who started an atypical antipsychotic drug, 9.6% died by 180 days. In adjusted analyses, patients who started a conventional drug were 32% more likely to die (hazard ratio=1.32; 95% CI, 1.23 to 1.42)—an excess of 3.5 deaths per 100 patients.


A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers

Kevin Thorpe, Merrick Zwarenstein, Andrew Oxman, and others

J Clin Epidemiology 2009;62:464-75.

“Pragmatic trials seek to answer the question: ‘Does the intervention work under usual conditions.’ ”

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The pragmatic to explanatory trials continuum*

Flexibility of comparisonintervention

PractitionerExpertise(experimental)

Flexibility of theexperimentalintervention

Eligibilitycriteria

Primaryanalysis

Practitioneradherence

Participantcompliance

Outcomes

Follow-upintensity

Practitionerexpertise(comparison)

E

* J Clin Epidemiology 2009;62:464-75


New atypical

antipsychotic drug

New conventional antipsychotic drug

No antipsychotic drugs filled: year-long baseline

Time

Zero

Intention-to-treat analyses to 180 days

A pragmatic cohort study: new users


Evaluating medication effects outside of clinical trials:New-user designs

Wayne Ray

Am J Epidemiol 2003;158:915-20

“[P]revalent users can introduce two types of biases:(1) Underascertainment of events that occur early in therapy (2) Inability to control for predictors that may have been altered

by the study drugs.”

Prevalent users also preclude meaningful propensity scores.


One class of intervention

Usual care:New or current users?Consistency of alternatives?

Any criteria for medications filled in year-long baseline?

Time

Zero

Valid comparisons with usual care?

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How might we design a score to predict the usefulness of pragmatic cohort studies?

How well does the cohort answer decision-makers’ questions?Inferiority or non-inferiority?

How closely does the cohort resemble a pragmatic trial? Design? Analysis?

How easy is the cohort for systematicreviewers to GRADE and synthesize?An unintended outcome, a harm?

.

Copyright 2006 Ethan Myerson iStockPhoto.com

“[A] national CER programshould promote the professional ethos that places the interests ofpatients and the largercommunity above all otherconsiderations.”

Harold Sox and Sheldon GreenfieldAnnals of Intern Med 2009;151:203-5

Comparative effectivenessresearch: a report from theInstitute of Medicine

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“He wants to look at his plate,see a steak, and say,‘I like steak!’ ”

“Give people what they want,then later you can give themwhat you want.”

Pascal in Big Night (1996)


Variation in the risk of suicide attempts andcompleted suicides by antidepressant agentin adults

Sebastian Schneeweiss, Amanda Patrick, Daniel Solomon, Jyotsna Mehta,Colin Dormuth, Matthew Miller, Jennifer Lee, Philip S Wang

Archives of General Psychiatry 2010;67:497-506


Design, intervention and control:Advanced strategies for propensity scores

“After plotting and comparing the distribution of propensity scores…we truncated our study population to the area of overlap. [S]ubjects with non-overlapping propensity scores mayhave absolute clinical indications or contraindications for aparticular treatment.”



“We constructed a high-dimensional propensity score based on the top 500 identified variables in addition to the variablesidentified by us…We consider results from this analysis to be the most completely adjusted… ”



“We created adjusted Kaplan-Meier plots by weighting eachsubject by the inverse of his or her probability for treatmentas estimated in the propensity score analysis.”

Sertraline vs. fluoxetine

Time since treatment initiation (months)

0 3 6 9 12

Com

posi

te e

vent

-fre

e pr

obab

ility

0.994

0.996

0.998

1.000

SertralineFluoxetine

Probability of remaining free of suicide or suicide attempt since treatment with sertraline (36,135) or fluoxetine (22,207), weighted by the inverse probability of treatment from the propensity score.From Schneeweiss et al. Arch Gen Psychiatry 2010;67:497-506

Copyright H Photography 2006 iStockphoto.com Pragmatic cohort studies and comparative effectiveness...

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