Critical Appraisal for MRCGP

1. Critical Appraisal for MRCGP Jim McMorran Coventry GP GP trainer Editor GPnotebook (www.gpnotebook.co.uk)

2. Can all elephants be washed by children?

3. Analysing studies • Confounding factors.. • Sample size.. • Applicability of results.. • Placebo controlled.. • Blinded… • Primary endpoints…

4. Critical Appraisal Methodology(from GPnotebook) • what is the research question - for most studies there should be a single sentence describing why the study was done and what hypothesis the authors were testing • the type of study design used • the study population investigated • comparator drugs and doses studied • sample size and power used in the study • primary versus secondary endpoints and subgroup analysis • duration of the study • study follow-up • is there a sponsorship or publication bias

5. Critical Appraisal Methodology(from GPnotebook) • other considerations • intention to treat analysis • what p-values are used • what confidence intervals are used • comparing statistical and clinical significance of results • analysis of results e.g absolute risks, relative risks, odds ratios, hazard ratios, numbers needed to treat, numbers needed to harm, Kaplan-Meier survival curves, simple statistical test

6. Research question • PROACTIVE (PROspective pioglitAzone Clinical Trial In macroVascular Events) • to find out whether pioglitazone reduces cardiovascular (CV) morbidity and mortality in high-risk patients with type 2 diabetes

7. Type of Study Design Used • Type of study: • retrospective e.g. case control study • prospective e.g. cohort study, randomised controlled trial • Other points regarding study design include: • was the study blinded? If so was the study blinded for the patient and the investigator (double blinded)? • was the study a crossover study? • The findings from a prospective study are more valid than those from a retrospective one

8. Different outcomes Different studies • Coronary Heart Disease and HRT • CHD and HRT - General Practice Notebook • Management of febrile child – use of tepid sponging or not? • prevention - General Practice Notebook

9. Study Population investigated • Age of population • Exclusion criteria used • study population - General Practice Notebook

10. Study populations investigated • Age when statins are effective • Statins effective for primary prevention up to the age of 70 years • WOSCOPS - General Practice Notebook • Statins effective for primary prevention up to the age of 85 years • MRC / BHF Heart Protection Study - General Practice Notebook • Is the study population comparable to those patients in primary care • Proactive study - General Practice Notebook • FIELD study - General Practice Notebook

11. Comparitor drugs and doses studied • Is there a comparitor Drug • comparator drugs in statistical studies - General Practice Notebook

12. Interesting comparisons • Bupropion versus varenicline for smoking cessation • varenicline - General Practice Notebook • Is the indicated length of use of medication the same for both medications • Exercise versus use of metformin in prevention of diabetes • exercise in the prevention of type 2 diabetes - General Practice Notebook • What about the dose of metformin

13. Sample Size and Power • What is statistical power? • What is the typical value of the power of the study? • Why is the power of the study important when considering study endpoints? • sample size and power of study - General Practice Notebook

14. Sample Size and Power

15. Power = 1 – type II error Higher Power Occurs with Less Overlap of Distributions

16. Primary Versus Secondary Endpoints • The power of a study is based on the primary endpoint of a study • primary versus secondary endpoints - General Practice Notebook • Headline studies where the primary endpoint was not significant include • Proactive study - General Practice Notebook • FIELD study - General Practice Notebook

17. Duration of study • Sufficient period to allow events to occur • Long enough to relate findings to use in chronically ill patient • duration of study - General Practice Notebook • Efficacy of topical NSAIDs versus oral NSAIDs • topical non-steroidal anti-inflammatory drugs (NSAIDs) in osteoarthritis - General Practice Notebook

18. Study follow-up • Affects the power of the study • study follow-up - General Practice Notebook

19. Is there sponsorship or publication bias • Is the study sponsored by the pharmaceutical industry or government sponsored • is there sponsorship or publication bias - General Practice Notebook

20. Other considerations – a selection • Intention to treat analysis • intention to treat analysis - General Practice Notebook • Comparing statistical and clinical significance • statistical versus clinical significance - General Practice Notebook • NNT • number needed to treat (NNT) - General Practice Notebook • Consider how many patients are required to be treated to prevent a single stroke based on the SPARCL trial (look at CIs) • SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial - General Practice Notebook

21. The End..