1. Corso di clinical writing

2. What to expect today? Core modules IntroductionIntroduction General principlesGeneral principles Specific techniquesSpecific techniques Title/Abstract draftingTitle/Abstract drafting Finding out relevant literature, and Introduction draftingFinding out relevant literature, and Introduction drafting Nuts & bolts of statistics and Methods draftingNuts & bolts of statistics and Methods drafting Practical session 1 – Appraisal of a published articlePractical session 1 – Appraisal of a published article

3. Which were the authors’ goals? The main goals in preparing a manuscript are full reporting and disclosure of relevant aspects of the study Is there any risk of bias? What are the findings? Do your findings apply to the my current clinical problem?

4. Case study Nelson et al, NEJM 2004

5. Useful appraisal approaches 1.The peer-reviewer approach 2.The Cochrane Collaboration approach 3.The EBM approach -> RECOMMENDED

6. Focused, structured and analytic approach BMJ guidelines for peer-reviewers: 1 - What is the paper about? 2 - Why was the study done? 3 - What type of study was done? 4 - Was it primary research (RCT, cohort, case-control, cross-sectional, series)? 5 - Was it secondary research (overview, systematic review, meta-analysis, decision analysis, guidelines development, economic analysis)? 6 - Was the design appropriate (for study on treatment, diagnosis, screening, prognosis, or causation)? 7 - Was the study ethical? 8 - Is the design right? A - Does this treatment work? → systematic review, RCT B - How good is a diagnostic test? → (prospective) cohort study C - Should we screen? → RCT D - What causes this disease? → RCT, cohort, case/control (rare diseases) E - What did people think or do? → cohort, cross-sectional survey, qualitative study

7. Self-criticisism while “studying a study” BMJ scoring tool for peer-reviewers Schroter et al, JAMA 2006

8. Internal validity appraisal according to The Cochrane Collaboration http://www.cochrane.org 4 MAIN TYPES OF BIAS POTENTIALLY UNDERMINING STUDIES Ascertainment biasAscertainment bias Non-uniform adjudication of events Attrition biasAttrition bias Non-uniform follow-up or compliance to treatment Performance biasPerformance bias Non-uniform performance of corollary treatments Selection biasSelection bias The non-random allocation of pts one of the treatment groups

9. The EBM 3-step approach How your article should be appraised, in three steps: Step 1 – Are the results of the study (internally) valid? Step 2 – What are the results? Step 3 – How can I apply these results to patient care?

10. EBM: Articles about therapy Are the results valid?Are the results valid? Did experimental and control groups begin the study with a similar prognosis? Were pts randomized?Were pts randomized? Was randomization concealed?Was randomization concealed? Were pts analyzed in the groups to which they were randomized?Were pts analyzed in the groups to which they were randomized? Were pts in the treatment and control groups similar with respect to known prognostic factors?Were pts in the treatment and control groups similar with respect to known prognostic factors? Did experimental and control groups retain a similar prognosis after the study started? Were pts aware of group allocation?Were pts aware of group allocation? Were clinicians aware of group allocation?Were clinicians aware of group allocation? Were outcome assessors aware of group allocation?Were outcome assessors aware of group allocation? Was follow-up complete?Was follow-up complete?

11. EBM: Articles about therapy What are the results?What are the results? How large was the treatment effect?How large was the treatment effect? How precise was the estimate of the treatment effect?How precise was the estimate of the treatment effect? How can I apply the results to patient care?How can I apply the results to patient care? Were the study patients similar to my patient?Were the study patients similar to my patient? Were all clinically important outcomes considered?Were all clinically important outcomes considered? Are the likely treatment benefits worth the potential harm and costs?Are the likely treatment benefits worth the potential harm and costs?

12. Title Nelson et al, NEJM 2004 RANDOMIZED?

13. Abstract Nelson et al, NEJM 2004 NON-INFERIORITY MARGIN?

14. Introduction Nelson et al, NEJM 2004 OK! Follows KUQE Brief but clear

15. Methods Nelson et al, NEJM 2004 OK! Explicit selection criteria Documentation of expertise Specific procedural protocol Centralized randomization

16. Methods Nelson et al, NEJM 2004 OK! Explicit follow-up criteria Independent adjudication Justification for sample size Clarification on non-inferiority

17. Results Nelson et al, NEJM 2004 OK! Trial profile Reasons for high drop-in (20%) BUT No details on non-enrolled pts Miss confidence intervals Lacks per protocol analysis

18. Results Nelson et al, NEJM 2004 OK! Trial profile Reasons for high drop-in (20%) BUT No details on non-enrolled pts Miss confidence intervals Lacks per protocol analysis

19. Discussion/Conclusions Nelson et al, NEJM 2004 OK! Comprehensive but concise Include disclosures of support BUT No conflicts of interest?

20. Discussion/Conclusions Nelson et al, NEJM 2004 OK! Comprehensive but concise Include disclosures of support BUT Cost implications? External validity? No conflicts of interest?

21. Figures Nelson et al, NEJM 2004 OK! Detailed but synthetic BUT Miss confidence intervals

22. Questions?

23. Take home messages 1.Criticizing constructively even the apparently most rigorous study is a very useful exercise 2.As long as you apply the same constructive criticism to yourself, your writing skills will continue to improve

24. And now have a good dinner…