How to Analyze Therapy in the Medical Literature: practical session

Akbar Soltani.MD.Tehran University of Medical Sciences (TUMS)

Shariati Hospitalwww.soltaniebm.com

Clinical question

• In passengers on long-haul flights, does wearing elastic compression stockings, compared to not wearing elastic stockings, prevent DVT?

Search terms

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

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.

Authors’ conclusion

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

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?

Randomized control trial design

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)?

Randomization and allocation concealment

• ‘Although the stockings were allocated randomly, …..

• See ‘Volunteers and methods: Randomisation’ (DVT trial p 1486).

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)?

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).

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.

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).

Evaluation

C1, p5, 1486

Evaluation

C1, p5, 1486

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).

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)?

Baseline characteristics

C2, p2, 1486

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)?

Losses to follow-up

Losses to follow-up

• 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

Results

C2, p2, 1486 , c1, p1, 1487

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.

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)?

Statistics

C2, p1, 1486

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?

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 = 10See ‘Results’, (DVT trial p1487).

Results

C1, p2, 1487

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?

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.

Thank You !