Core modules

1. RICERCA CLINICA IN CARDIOLOGIA INTERVENTISTICA (2/2)PercorsodidatticobasatosullarevisioneedinterpretazionedeidatiderivantidallaletteraturascientificaGiuseppe BiondiZoccai, Divisione di Cardiologia 1, Ospedale S. Giovanni Battista “Molinette”, Torinogbiondizoccai@gmail.com – http://www.metcardio.org

2. What to expect? Core modules • Introduction • Finding out relevant literature • General guidelines for literature appraisal • Abstract and Introduction appraisal • Methods and Results appraisal 1 - Patients and procedures • Methods and Results appraisal 2 - Data collection/management and descriptive analysis • Methods and Results appraisal 3 - Inferential analysis • Discussion and Conclusions appraisal

3. Topics of this presentation • Study design • Patient characterization • Procedures • Follow-up • End-points • Additional analyses

4. Topics of this presentation • Study design • Patient characterization • Procedures • Follow-up • End-points • Additional analyses

5. Study design • The study design should be clearly stated either in the end of the Introduction, or in the Methods • BEWARE IF IT IS NOT CLEARLY STATED! • Focus on prospective vs retrospective design • Clarify whether the study was single or multicenter • Is the study beneficial to any third party (eg sponsor)? If yes, assess whether it was spontaneous or funded, and whether any conflict of interest is present • Remember, not telling the whole truth is much more common than telling lies, but nonetheless may be done on purpose to fool the readers!

6. Study design Ardissino JAMA 2004

7. Topics of this presentation • Study design • Patient selection/characterization • Procedures • Follow-up • End-points • Additional analyses

8. Patients • Clear statements on the selection of patients are pivotal • to explicitly identify the target population • BEWARE IF THEY ARE NOT CLEARLY STATED! • Focus on inclusion vs exclusion criteria • Focus on consecutive vs purposeful enrolment • Is the patient population highly selected or are they everyday subjects? • Do authors provide separate numbers of patients screened, enrolled and randomized • Remember, a highly selected population will provide more internally valid answers, but at the price of lower external validity

9. Patients Ardissino JAMA 2004

10. Patients

11. Patients Biondi Zoccai Ital Heart J 2003

12. Topics of this presentation • Study design • Patient selection/characterization • Procedures • Follow-up • End-points • Additional analyses

13. Procedures • Clear statements on the interventional procedures are pivotal to ensure reproducibility of outcomes • BEWARE IF THEY ARE NOT CLEARLY STATED! • Focus on technical aspects, devices, and safety measures • Additional therapies are important as well (eg thienopyridines) • Can the techniques described be reasonably performed in other cath labs with the available equipments and expertise? • Do authors provide accurate data on the management of all scenarios (even the worst case one)? • Remember, centers with a specific expertise in a technique or device might provide results that are not easily reproducible by others

14. Procedures Ardissino JAMA 2004

15. Procedures

16. Procedures Colombo CCI 2005

17. Topics of this presentation • Study design • Patient selection/characterization • Procedures • Follow-up • End-points • Additional analyses

18. Follow-up • Follow-up procedures should be standardized and equally applied to all relevant patient groups • Focus on follow-up techniques (eg lab tests, ECG, phone interview, office visit,…) • Clearly identify follow-up duration (mean, median, standard deviation, range,…). Is it similar in the groups being compared? • Was enrolment going over for a long time or limited to a brief time frame? • Were there drop-outs, drop-ins, non-compliant pts, or losses to follow-up? • Remember, for clinical studies a >95% follow-up is mandatory to limit the risk of attrition bias

19. Follow-up Holmes JAMA 2006

20. Follow-up Holmes JAMA 2006

21. Follow-up Ardissino JAMA 2004

22. Topics of this presentation • Study design • Patient selection/characterization • Procedures • Follow-up • End-points • Additional analyses

23. End-points • Clear statements on the primary, secondary, and additional end-points are paramount. In case of doubt, remain skeptical! • BEWARE OF SECONDARY END-POINTS OR SUB-GROUP ANALYSES! • Focus on the primary end-point, as this was the only one for which the study was truly powered • Check for spurious inconsistencies between primary vs secondary or efficacy vs safety end-points • Were outcome assessors unaware of treatment assignment? • Sub-group analyses are by definition (unless otherwise stated) hypothesis-generating. In any case, the risks of alpha error and biological non-plausibility apply

24. End-points Ardissino JAMA 2004

25. End-points Holmes JAMA 2006

26. End-points

27. Topics of this presentation • Study design • Patient selection/characterization • Procedures • Follow-up • End-points • Additional analyses

28. Additional analyses • Additional analyses (eg, QCA, IVUS, TIMI flow, troponin release) are important in that they may drive the primary end-point (eg, TLR) or substantiate it indirectly (eg TIMI flow) • Focus on technical aspects, devices, software and reproducibility • Was personnel involved in additional analyses unaware of treatment assignment? • Beware of tautology issues • Some studies may indeed have more a pathophysiological than a clinical edge • Remember that additional analyses should • be distinguished from cosmetic analyses

29. Additional analyses

30. Additional analyses Windecker NEJM 2005