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Clinical trials are serious business. In addition to being big business (untold billions of dollars every year), they also involve serious ethical issues and choices. We are all aware of the fundamental ethical principle of informed consent
underlying all clinical trials.
What is less obvious is that conducting a clinical trial carries with it the responsibility to obtain and share results - whether they are positive or negative or even if the clinical trial is a failure. It is a failure - indeed a tragedy - when the lessons learned from such studies are not fully appreciated.
Clinical trials involving surgery - and by implication medical devices - are especially problematic. While placebo-controlled trials for pharmaceuticals are pretty well accepted from a statistical, practical, and ethical standpoint, the same cannot be said for controlled trials for surgery involving sham procedures - surgeries in which the patient is opened but no actual therapeutic intervention takes place. Instead, such trials are often designed to compare surgery with some other, non-surgical, treatment.
In this column, I will discuss one of these trials - the recent Spine Patient Outcomes Research Trial (SPORT) trial as published in the Journal of the American Medical Association
(JAMA) last November - and share with you, from my perspective, one of the most important lessons learned. Nothing definitive
JAMA articles titled Surgical vs. Non-operative Treatment for Lumbar Disk Herniation: The Spine Patient Outcomes Research Trial (SPORT) Observational Cohort
and Surgical vs. Non-operative Treatment for Lumbar Disk Herniation: The Spine Patient Outcomes Research Trial (SPORT): A Randomized Trial
summarized this important clinical trial. They were also accompanied by two editorials and the trial results were significant enough to raise the attention of the national media, including an article
in the New York Times
- Study Questions Need to Operate on Disk Injuries.
Indeed, it seems there as many cures for back pain as there are people with back pain. For anybody with excruciating back pain, it would be an incredible relief (to put it mildly) to have a definitive answer (finally) on what works and what doesn't work.
There's one problem though. This clinical trial - the largest and most comprehensive of its kind - could not provide a definitive yes or no answer. Instead, the basic conclusion was that discectomy relieved the back pain more quickly but that most people eventually improved in equal fashion and that conservative waiting did not seem to cause harm.
Even this conclusion - tenuous as it may seem - was significantly muddied by the rather unique trial design. In order to accommodate the challenges of conducting a surgical trial (in this case comparing surgery with conservative treatment involving patient education, anti-inflammatory medication, and/or physical therapy) as well as the fact that medical opinion was strongly in favor of surgery, the trial was designed so that patients could refuse to be randomized to one of the two treatment arms.
That is to say, both before and during the course of the trial, patients could request to crossover to the other treatment. Patients who were initially on the conservative treatment arm could decide that they couldn't stand it any more and would elect surgery. Other patients who were scheduled for surgery could decide they didn't want to accept the risk and went instead for physical therapy.
Because of the extremely high numbers of crossovers (45 to 60 percent of patients) and, to a lesser extent, a certain degree of missing data, such analyses are significantly confounded and should not be used to compare different strategies, as Dr. David Flum, a contributing editor at JAMA, wrote in his accompanying editorial
Instead of answering the question of which treatment was better, the trial seemed to suggest another important message. Dr. James Weinstein, a professor of orthopedic surgery at Dartmouth College
and the lead author of the study, said that regardless of the treatment,
nobody got worse [and that] we never knew that until we did the study. The New York Times article also quoted Dr. Flum:
Everyone was hoping the study would show which was better. And everyone was surprised by the tremendous number of crossovers in both directions, [Dr. Flum] added, referring to the large number of participants who changed from surgery to waiting and vice versa. That muddied the data.Crossover vote
It would seem, however, that this huge crossover rate also provided another, extremely important lesson. Namely, that patients not only value a good outcome, but they also value choice.
The starkly dichotomous nature of the treatments (e.g. surgery vs. waiting) and the high number of crossovers clearly sends a message that patient choice is absolutely critical and integral to the therapeutic process. For treatments whose outcomes are roughly equivalent, the availability of options may be much more important for patients than necessarily the usual indices of outcomes, morbidity, and so forth.
Who knows why some patients chose surgery - did they want to get it over with? or did they have lower short-term pain thresholds than those who elected to wait it out? What about those who chose not to go under the knife? Where their pain thresholds higher yet their risk tolerance less? While the study yielded indefinite results, this much is for sure: patients want (and certainly act upon) choice.
It was a bit disappointing then to read further in the JAMA editorials that designing clinical trials with sham-controlled surgeries (e.g. operations in which the patient is cut but the actual restorative procedure not done) may be the only effective and ethical next step. While I can understand the sentiments behind that, I think that the holy grail of scientific rigor does raise some questions.
Evidence-based medicine is certainly a critical component of rigorous, scientific medicine, but rigidly applying the concept that one and only one treatment must certainly prevail does a disservice to the diversity of experience, expectations, and circumstances that enter into any medical decision. It is believed that randomized, double-blind clinical trials are the cure against biased medical decisions. However, this blinds one to perhaps the most important bias - the notion that there should be a binary (yes or no) outcome to any treatment comparison.
While the SPORT trial was, in relative terms, a limited success with less than definitive results, it would be an even greater failure to not recognize the larger lesson learned. Whether right or wrong: patients do value choice.Previous articles by Dr. Ogan Gurel
Ogan Gurel: Healthcare of business: Universal coverage plan includes new business taxes
Ogan Gurel: And the winners in medical design are
Ogan Gurel: A prognosis for GE and Abbott Diagnostics
Dr. Ogan Gurel: Lance Armstrong and the future of cancer care
Dr. Ogan Gurel is chairman of the Aesis Research Group, which provides forward-looking information and research services to the healthcare and life sciences investment community. Gurel was previously CEO of Duravest, a publicly traded Chicago investment company that initiates and develops next-generation medical technologies. Previous to Duravest, he was a vice president and medical director at Sg2, a healthcare intelligence think tank and consultancy serving hospitals and health systems. He can be e-mailed at firstname.lastname@example.org
This article previously appeared in MidwestBusiness.com
, and was reprinted with its permission.
The opinions expressed herein or statements made in the above column are solely those of the author, and do not necessarily reflect the views of Wisconsin Technology Network, LLC.
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