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The epistemology and ethics of chronic disease research: Further lessons from ECMO

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Abstract

Robert Truog describes the controversial randomized controlled trials (RCTs) of extracorporeal membrane oxygenation (ECMO) therapy in newborns. Because early results with ECMO indicated that it might be a great advance, saving many lives, Truog argues that ECMO should not have been tested using RCTs, but that a long-term, large-scale observational study of actual clinical practice should have been conducted instead. Central to Truog’s argument, however, is the idea that ECMO is an unusual case. Thus, it is an open question whether Truog’s conclusions can be extended to other areas of medical research. In this paper, I look at epistemological and ethical issues arising in the care of patients with chronic diseases, using ECMO as a starting point. Both the similarities and the dissimilarities of these two cases highlight important issues in biomedical research and support a conclusion similar to Truog’s. Observational studies of clinical practice provide the best evidence to inform the treatment of patients with chronic disease.

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Notes

  1. James Ware outlines the sample size calculations used in the design of this study [7]. He shows that using the expected survival rates (based on previous studies) for both ECMO and conventional therapy and continuing Phase I until four deaths had occurred in one group would have a power of .77, compared with .55 for three deaths and .84 for five deaths (all calculated for a Type I error rate of .05). The study designers chose to continue Phase I until the fourth death in one arm on the basis of these power calculations.

  2. For further discussion of the relationship between ethical and epistemological issues in the ECMO trials, see [10].

  3. In addition to Truog’s article, the ECMO studies were debated in two issues of the journal Statistical Science, which published two target articles drawing on the ECMO case [7, 11], together with a series of replies to each article. Ware, one of the researchers who conducted the second ECMO trial, defends the trial design as a compromise between ethical and methodological concerns [7]. Royall [11] and Berry [12] reach conclusions about the ECMO research that are similar to Truog’s. In all of these discussions, there is a general consensus that ECMO is a special case.

  4. Part of the rationale for using a control group is to account for spontaneous recovery rates in each group. The fluctuations in symptom severity that occur in chronic diseases present a more complex version of this problem.

  5. Note, too, that the common practice of prescribing doses of a drug that differ from the “standard” regimen tested in clinical trials further calls into question the generalizability of RCTs of any treatment.

  6. Restricting trial entry to patients newly diagnosed and previously untreated for the disease in question would be one possible response; however, in addition to adding greatly to the time required to recruit sufficient patients for a trial, it is also ethically questionable (as argued, for example, by AIDS activists, see [18]) and raises the question of the generalizability of the results of the trial to patients with longer-standing diseases.

  7. It should also be noted that, in general, EBM tends to recommend that subgroup analyses be viewed with skepticism; see, e.g., [27, pp. 160–161]. If this attitude is generally accepted, this would mean that subgroup analyses may not be done, even in large pragmatic trials.

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  1. Department of Philosophy and Religious Studies, Old Dominion University, Norfolk, VA, 23529, USA

    Robyn Bluhm

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Bluhm, R. The epistemology and ethics of chronic disease research: Further lessons from ECMO. Theor Med Bioeth 31, 107–122 (2010). https://doi.org/10.1007/s11017-010-9139-8

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