Clinical Trials versus Real Life

The next issue of The Medical Letter (December 22, 2014) will be on Drugs for Rheumatoid Arthritis. In the course of preparing that issue, we were faced with a dilemma. One of our senior reviewers with a long history of treating patients with rheumatoid arthritis asked us to omit the results of a published clinical trial that we had mentioned briefly in an early draft. The study in question (JR O’Dell et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med 2013; 369:307) found that in patients who had not responded to methotrexate, adding a combination of hydroxychloroquine and sulfasalazine was non-inferior to adding the TNF inhibitor etanercept (Enbrel). Our reviewer said, in effect, everybody knows that’s not so.

We asked a second reviewer, could adding those 2 relatively inexpensive old drugs really be as effective as adding a TNF inhibitor? His clinical experience, he said in effect, would lead him to believe that they could not. But the study was a good study, he added, and the controlled conditions of a clinical trial are not the same as those of clinical practice.

We took another look at the study. It was a 48-week, double-blind trial in 353 patients. The primary outcome was improvement in disease activity scores at week 48. Both groups improved significantly, the change in scores from baseline was similar, and there was no significant difference in radiographic progression of the disease. The study did show, however, a clear trend toward a more rapid response in the etanercept group, and the authors speculated that a more rapid response early in therapy might predict a longer-term benefit. And the percentage of patients with the highest level of response at 24 weeks was higher with etanercept than with hydroxychloroquine/sulfasalazine.

So what should we do? Stick to the evidence (the results of the study)? Honor the clinical experience of our consultants by emphasizing the authors’ caveats? Poll more experts? I think I know the answer, but I’m not sure, and other editors may have persuasive arguments for another approach. So watch for our article. It will be available online on December 17th.

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  1. Robert Schrock MD retired orthopaedic surgeon says:

    Terrific! If all physicians had been led to your publication the way I was and had received the type of skeptical pharmacology education dispensed at Cornell in 1963, we might be practicing better medicine in this country now. I am retired and no longer can justify the cost of your subscription, but your blog keeps my juices flowing. Thank you!

    Bob Schrock
    Chapel Hill, NC

  2. Gust Stringos D.O. says:

    I don’t know the answer to this question, but I appreciate that you are asking it. There is so ugh conflict of interest in medical studies- do the authors have conflicts of interest? Do the critics have conflicts of interest? I appreciate that Medical Letter tries to sort this out.

    Gust Stringos, D.O., F.A.A.F.P.

  3. Publish the evidence. There is less chance of bias there than in personal opinion/experience.

  4. Jeff Lazar says:

    Robert Temple at FDA loves to remind us (and I paraphrase) that the plural of anecdote is not data. While the opinion of a practicing physician is certainly valuable, it’s still not data. I echo the excellent comments of Dr. Schrock and Dr. Walker. Furthermore, it’s time that the practicing physician had the benefit of ALL the data, and then could make his/her own decisions. There is already enough biased information provided by various representatives of the regulated industry. The only thing all physicians have in common is the prescription pad, yet there is no mandate for continuing education in therapeutics. You do that beautifully on your blog (as does The Cochrane Collaboration) — don’t back down because one of your reviewers wants to impose his/her bias on your readership!

    Jeffrey D. Lazar, MD, PhD

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