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Mindstretcher: Making Decisions for Guidelines

Choices
Results
Exposure
Comment

This short piece is by way of being a reminder that making decisions about evidence is not always easy. You are going to be presented with some evidence about an important topic, drawn from a Cochrane review. You will have to choose how you word this in your guidelines.

Choices


There are three choices (A, B, or C) for a medicine that can reduce the likelihood of a serious, potentially fatal, event. Randomised trials have been conducted on identical patient groups, over roughly the same period of time, and using the same outcome.

Results


The results are shown in Table 1, and in Figures 1-3.


Table 1: Results for meta-analyses of trials of A, B, and C



Number of
Percent bad events with
Intervention
Trials
Patients
Intervention
Placebo
Relative risk
(95% CI)
NNT
(95%CI)
A
3
298
15
36
0.4 (0.3 to 0.6)
4.6 (3.2 to 8.4)
B
3
981
10
15
0.6 (0.4 to 0.9)
18 (10 to 65)
C
5
1216
15
36
0.4 (0.3 to 0.5)
4.7 (3.8 to 6.2)




Figures 1-3: Individual trial results with (from top) A, B, and C













What do you use to choose? Here are some thoughts.

Medicine A had too few patients to be sure of the result. The problem with B is that while it produced the best result in terms of the lowest number of events, the rate with placebo was also low, yielding higher (worse) relative risk and NNT. Is the low rate with intervention a reflection of a different population (probably not), chance (probably not), or some other, unknown, feature of these particular studies (though some studies with other treatments had this characteristic; look at Figure 3)? Is medicine C the only safe choice?

Exposure


These data are for total endoscopic ulcers in trials lasting 3-12 months, from a Cochrane review updated in 2004 [1]. The treatments were:

A – High dose H2A (equivalent to at least 300 mg ranitidine twice daily)
B – Low dose H2A (equivalent to 150 mg ranitidine twice daily)
C - PPI

Comment


Most guidelines suggest using PPI or high dose H2A. To do so, they do not rely on these placebo-controlled studies alone. Nor should they, because the amount of information is limited, and these are, after all, at best surrogate measures for much more complicated events.

This is a case where a single direct comparison can really help. For instance, a large study compared omeprazole 20 mg daily with ranitidine 150 mg twice daily in 425 patients, and found omeprazole much superior (6% endoscopic ulcers, compared with 21% with ranitidine). For high dose H2A we do not even have that luxury, other than a comparison of two doses of nizatidine, with just eight events.

Yet the advice to use double dose histamine antagonists seems to be almost universal. It is curious that so much can be made of so little.

Reference:


  1. A Rostrom et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database of Systematic Reviews, issue 1, 2006.

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