Transcript Appraisee Training Day - QResearch
The effect of the ‘Polypill’ on mortality in general practice
Dr Julia Hippisley-Cox Gozo October 2004
Goals of presentation
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To given an over view of electronic database used for the study (QRESEARCH)
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To describe research to determine effect of the ‘Polypill’ on mortality in patients with CHD
GP databases in the UK
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Several different database available
– Oldest and most well known GPRD • • •
QRESEARCH new key databases Both derived from GP clinical data Both available for access by researchers
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Both are an international resource
QRESEARCH What is it?
• • • •
QR is result of a not-for-profit partnership between UoN & EMIS [supplies > 60% all practices] Patient level consolidated database Longitudinal data for up to 16 years Validated against external and internal measures
Qresearch Coverage
• • • • • •
468+ practices UK wide > 5 in every SHA Approx 7.4 million patients including those who died, left and still registered 3.3 million current patients Now the largest such database in the world (unless anyone here knows otherwise!)
Data contents
• • • • • • •
Socio-demographics Diagnoses Clinical values Laboratory tests Prescription data Consultation data Category of clinician entering data
QRESEARCH Research service
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We will provide a service to Bona fide academics With original research question With MREC With freedom to publish Who agree to
- Acknowledge source data - use it for purpose only - not pass it on
What type of research can we use it for?
• • • •
Best for epidemiological studies Case control studies Cohort studies Cross sectional survey Modelling
Things we cant do:
• • • •
Track back to patients Track back to practices Randomise patients or practices Link with external data sources eg questionnaire, genetics
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This is where other systems come in
- THIN - e-GRID – UK Biobank
Aims of research project
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To determine the effect of the ‘Polypill’ on mortality in CHD patients
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Polypill = aspirin + beta blockers + ACE inhibitors + statins
Background to project
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Good evidence from individual trials for benefits of individual drugs in 2’ prevention CHD Enthusiasm for ‘Polypill’ for all patients over 55 years though no direct evidence benefits stack up
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Drugs may interact with drugs or other comorbidity
Design & setting
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Design Open cohort study with case control analysis
• •
Setting 1.18 million patients registered with 89 QRESEARCH practices on 1 1996 st Jan All practices had a minimum of 8 years of complete computerised data
Study cohort
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All patients with a 1 st CHD between 1 st diagnosis of Jan 96 and 31 Dec 2003
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Study period chosen as statins only in common use after Jan 96
Cases & controls
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Cases were CHD patients who died during study period
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Controls were CHD patients who didn’t die matched for
– Age – Year of birth – Sex •
Four controls per case
Index date
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Assigned index date to each case [date of death]
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Assigned same date to matched controls
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Reviewed medical & drug history prior to this date
Outcomes
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Odds ratio (95% CI) for all cause mortality in cases vs controls
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Exposure
– combinations of aspirin, statins, beta blockers and ACE inhibitors •
Adjusted for
– Comorbidity (MI, Diabetes, hypertension, CCF) – Smoking – obesity – deprivation
Statistics
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Conditional logistic regression using STATA v8.2
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Examined for 2 way interactions
– drug*drug – drug*disease •
Included significant interactions in model
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Selected p < 0.01
PRELIMINARY RESTULS study population 1.17 million patients in population 13,029 patients with CHD 2,266 deaths So 2,266 cases + 9064 matched controls
Comparison with 4S study
• • •
Patients on statins had 37% lower risk of death c.f. those not on statins This is similar to the 30% reduction in risk reported in 4S study Marginally greater benefit as our population higher risk than trial population
Odds ratio for death
Combination Adjusted odds ratio* Statin + aspirin + BB + ACE 0.63 (95% 0.51-0.79) Statins + aspirin + BB 0.43 (95% 0.34-0.55)
* Adjusted for CCF, diabetes, hypertension, MI, smoking, obesity, deprivation etc
In other words
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Despite adjustment for comorbidity, patients on combination of :
– 3 drugs had 57% lower risk of death – 4 drugs had 37 % lower risk of death •
Combination without ACE was better
Discussion of methodology
• • • •
Case control study but Very large sample No recall bias No selection bias Misclassification unlikely as drugs all prescribed except aspirin which is also OTC
Possible explanations
• • •
We found significant statistical interaction between ACEI and statins Possible explanations
– ? misclassification of CCF (but no interaction between other drugs) – ? Chance finding
Whatever, study challenges assumptions that benefits automatically stack up in ‘real life populations’