1. How to Analyze Therapy in the Medical Literature: practical session Akbar Soltani.MD. Tehran University of Medical Sciences (TUMS) Shariati Hospital www.soltaniebm.com

2. Clinical question In passengers on long-haul flights, does wearing elastic compression stockings, compared to not wearing elastic stockings, prevent DVT?

3. Search terms Based on the clinical question (PICO), we used the following search terms: (flight* OR travel*) AND stocking* AND (DVT OR thrombosis)

4. Search results PubMed Clinical Queries (therapy, broad), 20 hits (referring to 5 studies and several reviews, including one recent Cochrane review) For this exercise we have chosen the following study to look at in more detail: Scurr et al (2001). Frequency and prevention of symptomless deep-vein thrombosis in long- haul flights: a randomised trial. Th e Lancet 357:1485–1489.

5. Authors’ conclusion ‘Wearing of elastic compression stockings during long-haul air travel is associated with a reduction in symptomless DVT.’

6. Three Step Guide in Using an Article to Assess Therapy 1.Are the results of the study valid? 2.What are the results? What measures of precision of effects were reported (CIs, p- values)? 3.How can I apply these results to patient care?

7. Randomized control trial design

8. Assess Validity and Applicability to my practice setting 1.Is the study a randomized control trial (RCT)? Yes (go on) No (stop) 2.Were the patients properly selected for the trial and randomized with concealed assignment? Yes (go on) No (stop) 3.Were patients and study personnel “blind” to treatment? Yes (go on) No (pause) 4.Were the intervention and control groups similar at the start? (Check “Table 1” of most studies) Yes (go on) No (stop) 5.Was follow-up complete? ii. Were patients analyzed in the groups to which they were randomized (“intention-to-treat” analysis)?

9. Randomization and allocation concealment ‘Although the stockings were allocated randomly, ….. See ‘Volunteers and methods: Randomisation’ (DVT trial p 1486).

10. Assess Validity and Applicability to my practice setting 1.Is the study a randomized control trial (RCT)? Yes (go on) No (stop) 2.Were the patients properly selected for the trial and randomized with concealed assignment? Yes (go on) No (stop) 3.Were patients and study personnel “blind” to treatment? Yes (go on) No (pause) 4.Were the intervention and control groups similar at the start? (Check “Table 1” of most studies) Yes (go on) No (stop) 5.Was follow-up complete? ii. Were patients analyzed in the groups to which they were randomized (“intention-to-treat” analysis)?

11. Blinding ‘Although the stockings were allocated randomly, the passengers were aware of the treatment’ (ie were not blinded). See ‘Volunteers and methods: Randomisation’ (DVT trial p 1486).

12. Blinding Using a ‘placebo’ stocking (a low-pressure stocking) would have been better as it would have blinded the subjects to which group they were in, thus reducing any tendency for the subjects in the two groups to behave differently during their flights.

13. Outcome assessors ‘Most passengers removed their stockings on completion of their journey. The nurse removed the stockings from those passengers who had continued to wear them. A further duplex examination was then undertaken with the technician unaware of the group to which the volunteer had been randomised’ (ie blinded) See ‘Volunteers and methods: Evaluation (DVT trial p 1486).

14. Evaluation C 1, p 5, 1486

15. Evaluation C 1, p 5, 1486

16. Outcome assessors The outcome measured in the DVT trial (symptomless DVT in the calf) was subject to some interpretation by the ultrasound technician, making blinding of the technicians an important quality issue for this trial. See ‘Volunteers and methods: Evaluation (DVT trial p 1486).

17. Assess Validity and Applicability to my practice setting 1.Is the study a randomized control trial (RCT)? Yes (go on) No (stop) 2.Were the patients properly selected for the trial and randomized with concealed assignment? Yes (go on) No (stop) 3.Were patients and study personnel “blind” to treatment? Yes (go on) No (pause) 4.Were the intervention and control groups similar at the start? (Check “Table 1” of most studies) Yes (go on) No (stop) 5.Was follow-up complete? ii. Were patients analyzed in the groups to which they were randomized (“intention-to-treat” analysis)?

18. Baseline characteristics C 2, p 2, 1486

19. Assess Validity and Applicability to my practice setting 1.Is the study a randomized control trial (RCT)? Yes (go on) No (stop) 2.Were the patients properly selected for the trial and randomized with concealed assignment? Yes (go on) No (stop) 3.Were patients and study personnel “blind” to treatment? Yes (go on) No (pause) 4.Were the intervention and control groups similar at the start? (Check “Table 1” of most studies) Yes (go on) No (stop) 5.Was follow-up complete? ii. Were patients analyzed in the groups to which they were randomized (“intention-to-treat” analysis)?

20. Losses to follow-up

21. Research papers reporting RCTs should include a flowchart showing the numbers of subjects and their progress through the trial. The DVT trial flowchart shows: 231 subjects were randomised (115 to stockings; 116 none) 200 were analysed; that is, 31 were lost to follow-up as follows:  27 unable to attend for subsequent ultrasound  2 were excluded from analysis because they were upgraded to business class  2 were excluded from analysis because they were taking anticoagulants

22. Results C 2, p 2, 1486, c 1, p 1, 1487

23. How important were the losses? Were they equally distributed?  stockings: 15 lost (6 men; 9 women)  no stockings: 16 lost (7 men, 9 women) Did they have similar characteristics?  No other information is provided about the characteristics of the lost subjects.

24. Assess Validity and Applicability to my practice setting 1.Is the study a randomized control trial (RCT)? Yes (go on) No (stop) 2.Were the patients properly selected for the trial and randomized with concealed assignment? Yes (go on) No (stop) 3.Were patients and study personnel “blind” to treatment? Yes (go on) No (pause) 4.Were the intervention and control groups similar at the start? (Check “Table 1” of most studies) Yes (go on) No (stop) 5.Was follow-up complete? ii. Were patients analyzed in the groups to which they were randomized (“intention-to-treat” analysis)?

25. Statistics C 2, p 1, 1486

26. Three Step Guide in Using an Article to Assess Therapy 1.Are the results of the study valid? 2.What are the results? What measures of precision of effects were reported (CIs, p- values)? 3.How can I apply these results to patient care?

27. What do the results of the DVT trial mean? DVT in stocking group = 0 [absolute risk (AR) = 0%] DVT in control group = 10 [AR = 10%] Absolute risk reduction (ARR) = 10% – 0% = 10% This means that this study shows that absolute benefit of wearing stockings is a 10% reduction in symptomless DVTs. Number needed to treat (NNT) to avoid one case of DVT = 100/10 = 10 See ‘Results’, (DVT trial p1487).

28. Results C 1, p 2, 1487

29. Three Step Guide in Using an Article to Assess Therapy 1.Are the results of the study valid? 2.What are the results? What measures of precision of effects were reported (CIs, p- values)? 3.How can I apply these results to patient care?

30. Conclusion While the results show a reduction in symptomless DVT in passengers on long-haul flights, the study had some design flaws that would warrant further investigation of this issue. While an NNT of 10 is impressive, the importance of this remains a matter of clinical judgment about the consequences, such as the small number that may become symptomatic, the even smaller number of DVTs that may cause pulmonary embolism, and the uncertain number of people who will go on to develop postphlebitic syndrome some years in the future. That is a difficult judgment.

31. Thank You !