Ethics / Science of ARDS Controversy Continues – J Medical Ethics-BMJ

Ethics / Science of ARDS Controversy Continues – J Medical Ethics-BMJ

Thu, 6 Oct 2005

The ethics and science of a controversial clinical trial sponsored by the US government and conducted at multiple sites by the ARDS Network comprising of prestigious academic medical centers is the subject of a continuing heated debate . [1] [2]

In this controversial randomized experiment 861 critically ill patients, whose acutely injured lungs required the aid of a mechanical ventilator to deliver oxygen, were withdrawn from the individualized tidal volume (TV) ventilation settings prescribed by a critical care specialist (in accordance with standard practice). At the time of the ARDS experiment –1996-1999– the range in TV settings in standard care was between 6.5 ml/kg and 14.5 ml/kg.

The patients enrolled in the ARDS experiment were randomly assigned to one of two fixed TV ventilator settings–a low setting at 6 ml/kg or a high setting at 12 ml/kg.

Most patients were enrolled without their informed consent. [3]

And consent documents signed by others, failed to disclose that death was one of the risks of the experiment.

The experiment compared two fixed ventilator settings to which patients were randomized without regard for the condition of each patients’ lungs.

The experiment lacked a control arm (i.e., best standard of care) against which the two experimental methods could even be evaluated.

Thus, the experiment was not designed to answer the clinically relevant question whether either 6 ml/kg or 12 ml/kg was better or worse than standard care.

Of the 429 patients assigned to receive the fixed high tidal volume (12 ml/kg), 171 (40%) patients died. Of the 432 patients assigned the lower tidal volume (6 ml/kg), 134 (31%) died. Of the 260 eligible patients who did not enter the trial, 90 (31%) died. The ARDSNetwork investigators themselves concluded in their letter: “…critically ill patients who participated in this trial did not fare better overall than eligible patients who declined to participate.”  [4]

The experiment presents multiple concerns–including the demonstrable failure of the research protection system to protect patients from an experiment not designed to minimizae the risk of death. The institutional review boards (IRBs) in the ARDSNetwork approved an experiment that put patients’ lives at risk and was not designed to answer an improtant scientific question.

Critical care specialists who have criticized the ARDS trial design, argue (among other things) that critically ill patients such as these require individualized care and that the ventilator settings must be adjusted according to each patient’s condition on a continuing basis. Essentially they argue, one size does not fit all. [5]

The experiment has triggered a heated debate about the ethics and scientific merit of this, and perhaps other similar experiments in which federal requirements are dispensed.

The major medical research journals and bioethics journals have been unwilling to give equal opportunity to bothe sides of the debate–they have either been silent or given only the ARDS defenders an opportunity to be heard. Until now, only two specialized journals, The American Journal of Respiratory Critical Care Medicine and Critical Care Medicine have published both sides of the debate fairly. The New England Journal of Medicine has published numerous articles in defense of ARDS–including an editorial by its editor in chief–but declined to publish criticism by prominent critical care specialists. The debate, however, has recently been picked up by the Journal of Medial Ethics of the BMJ (British Medical Journal). [6]

References:

  1. See The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for the experiment. acute lung injury and the acute respiratory distress syndrome. N Engl History. J Med 2000;342:1301­1308.

  2. list of participating ARDS centers: http://www.ardsnet.org/links.php and http://www.ahrp.org/ARDSpages/ARDSNetMembers.php

  3. See OHRP Letter, Oct. 7, 2002, to: Ronald S. Newvbower, Ph.D(Mass. General Hospital), Lee E. Limbird, Ph.D. (Vanderbilt University), and Robert Kay, MD) (Cleveland Clinic Foundation) : http://www.ahrp.org/ARDSpages/ARDSindex.php

  4. Peter Q. Eichacker, Steven M. Banks, Charles Natanson, Letter to the editor AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 167: 798-800.

  5. See: Mechanical ventilation in ARDS: One size does not fit all, Editorial by Katherine J. Deans, Peter C. Minneci, Steven M. Banks, Charles Natanson, Peter Q. Eichacker, Critical Care Medicine, 2005; 33(5):1141.

  6. See: H Mann Controversial choice of a control intervention in a trial of ventilator therapy in ARDS: standard of care arguments in a randomised controlled trial J Med Ethics 2005; 31: 548-553 http://jme.bmjjournals.com/cgi/content/abstract/31/9/548 See: Letters: http://jme.bmjjournals.com/cgi/eletters/31/9/548 For documents relating to the debate and federal investigation findings, Search the AHRP website. See, for example: http://www.ahrp.org/ethical/ARDSinvestigation.php

Contact: Vera Hassner Sharav
212-595-8974
veracare ahrp org