;)
Randomized clinical trials, reversals: Randomized clinical trials, reversals
When Vinay Prasad, MD, was a resident, strict control of blood glucose for patients in the intensive care unit was considered an important goal. “We really chased tight glycemic control in the medical ICU, but of course, just a few years later, a randomized control trial—NICE-SUGAR—came out showing that that actually led to net harm without benefit,” he said.
That's just one example of a medical reversal, which occurs when new and superior research contradicts and supersedes existing clinical practice. It's a phenomenon in which Dr. Prasad, an associate professor of medicine at Oregon Health & Science University and the author of Ending Medical Reversal: Improving Outcomes, Saving Lives, is an expert.
He and a team of colleagues from OHSU published a comprehensive review of randomized clinical trials in the Journal of the American Medical Association, The Lancet, and the New England Journal of Medicine identifying 396 medical reversals. (eLife. 2019;8:e45183; http://bit.ly/348t3aV.)
At least a dozen of these reversals related specifically to emergency medicine, while many others had at least some relationship to emergency care, trauma, and critical care. A few examples:
- Mechanical chest compressions with the LUCAS device, in use since 2003 for treating patients in cardiac arrest, was found in the LINC randomized, controlled trial to have no significant effect on survival compared with manual CPR in patients with out-of-hospital cardiac arrest. The ability to achieve ROSC with the mechanical device was inferior to manual chest compression during resuscitation. (JAMA. 2014;311[1]:53; http://bit.ly/32a6ukk.)
- Early and aggressive intervention with the early goal-directed therapy (EGDT) protocol for ED patients in whom sepsis is suspected was widely adopted after one positive study in 2001. It was later found to confer no added survival benefit compared with usual care and to contribute to increased ICU resource utilization. (JAMA. 2017;318[13]:1233; http://bit.ly/2ZyY6cC.)
- The REACT-2 trial found that routine use of an immediate total-body CT scan as part of trauma workup did not reduce in-hospital mortality compared with conventional imaging and selective CT scanning in patients with severe trauma. (Lancet. 2016;388[10045]:673; http://bit.ly/2NDO0EQ.)
- Platelet transfusion after acute hemorrhagic stroke associated with antiplatelet therapy was a common practice in the ED (as well as in neurosurgery and stroke units), but the 2015 PATCH study found worsened survival in the platelet transfusion group (68%) compared with the standard care group (77%). (Lancet. 2016;387[10038]:2605; http://bit.ly/2NKGdFv.)
Aggressive Adoption
Jennifer Gill, an OHSU research scientist and an author with Dr. Prasad on the medical reversal study, said many of the articles reversed the idea of “the more aggressive, the better.” She said emergency medicine in particular is susceptible to adopting aggressive treatments because first-line clinicians deal with acute conditions.
“They have an extremely difficult job, and a lot of times they do need to be aggressive to save patients,” she said. “In emergency medicine, guidelines and protocols are continually changing to find effective practices.” Sometimes that leads practices to be implemented based on retrospective data or bioplausibility without rigorous testing. “The adoption of these practices may utilize resources and physician time unnecessarily, and they may put patients through harsher treatment without benefit,” Ms. Gill said. “Each reversal is different, but some may have a trickle-down effect as well. Administering opioids for acute pain in the ED was shown to be no more effective than NSAIDs in reducing pain, for instance.”
It's possible the increasing popularity of Free Open Access Meducation (FOAM) and other online sources of information and learning plays a role in adopting treatments and approaches before a true body of evidence supports them. Ms. Gill said it's a double-edged sword, and noted that these resources are extremely influential and critical to medical advancement, and sharing experience, research, and opinions has never been so easy and widespread.
But these opportunities to share information online can also lead to collaboration and innovation, Ms. Gill said, calling #Medtwitter, for example, a great platform for disseminating and discussing research, though it spreads a lot of misinformation at the same time. “It is an inevitable part of social media,” Ms. Gill said, which prompted the OHSU researchers to create a website as a resource for best practices. (www.medicalreversal.com.)
Medical reversals have occurred throughout the history of medicine, she said, and it's not clear that social media and internet learning increase the frequency of therapies being adopted into practice before they are fully tested. “Medical trainees are clever and thirsty for information,” she said. “They know how to navigate social media and the internet, and I think we will be pleasantly surprised by the new generation of practitioners. The danger, to me, is the way social media circulates medical information to the greater public—fad diets and expensive, ineffective drugs and hype about many practices that do have strong evidence to support their use.”
Clinicians must stay informed, continue to read and understand the latest research, and demand higher standards for their patients, Ms. Gill said. “We need to use the internet wisely and teach trainees how to critically appraise research to best understand their field. The real way to avoid reversals is to demand large, well-conducted, randomized trials on outcomes that matter to patients.”
Share this article on Twitter and Facebook.
Access the links in EMN by reading this on our website, or in our free iPad app, both available at www.EM-News.com.
Comments? Write to us at [email protected].
Ms. Shawis a freelance writer with more than 20 years of experience writing about health and medicine. She is also the author of Having Children After Cancer, the only guide for cancer survivors hoping to build their families after a cancer diagnosis. You can find her work atwww.writergina.com.
