Clinical Trials: You Can’t Always Get What You Want

–Trial investigators have lost control of their trials’ messages.

Editor’s Note: The following is a lightly edited version of a talk I presented (without slides!) at the CVCT workshop in Washington, DC earlier this week. The topic was the changing role of media in communicating the results of clinical trials.

When it comes to the role of media in communicating the results of clinical trials I have some bad news for this audience. In the past it may have been possible to “control” the message from a clinical trial. This is now no longer possible. You have lost control of media and you cannot control the message.

Earlier today the New England Journal of Medicine‘s John Jarcho pointed out that many trials published 20-30 years ago would not pass muster today. But many of those imperfect trials delivered results that profoundly and permanently altered the field of cardiology. The same can not be said of today’s trials.

In the beginning— and by the beginning I mean when I was new to the business— a big cardiology trial was easy to understand. As journalists we were told, and dutifully reported, what the trials meant and how they should be interpreted. Some of the first really important trials I reported in the late 1980s and early 1990s were GISSI, V-HeFT, ISIS-2, CONSENSUS, 4S, and GUSTO. It is difficult to convey now the excitement and interest that these trials generated at the time.

The messages from these trials could not have been more clear, and these were important messages. The thrombolytic trials were especially dramatic. The media took it upon ourselves to help our readers marvel at the remarkable developments in the field of cardiology, which had, for the first time, achieved something quite astonishing and praiseworthy. For the first time it had come up with new treatments for cardiovascular disease, the leading cause of death and disability in the developed world.

Often there was a commercial angle but we were too polite to talk about that, unless of course that was part of the story, like the “miracle” of Genentech’s TPA, the first genetically engineered drug.

There was broad harmony among the trial investigators, the medical societies, industry, regulators, and other interested parties about the importance of these trials and what they meant. It was easy to “control” the message. Over time the machinery to convey this message became increasingly efficient, peaking in the early 1990s with the GUSTO trial and the statin trials. If memory serves, GUSTO, now nearly 25 years ago, was the first trial with a simultaneous publication, considered an astonishing feat at that time. It was presented at a symposium that lasted several hours. The key point is that the GUSTO team, and their Genentech partners, had complete control of the process and the message. They achieved total victory. One of the biggest controversies in cardiology ever was, essentially, resolved in the course of a few hours.

The trials got even bigger— and so, we thought at first— even better and more important— but in truth they were bigger because they were only trying to show an incremental advantage. The easy work, it turns out, had been done, the low hanging fruit had been picked. I remember listening— and failing to comprehend— Richard Peto talk about the difference between placebo controlled trials and active controlled trials. It was a long time before I was able to understand his message.

Let’s jump ahead now to the COURAGE trial. Somehow it now seems appropriate that this came out in 2007, at the same time a far larger economic and political turmoil was starting to wreak havoc. Was COURAGE representative of something even larger? There had of course been many long and hard fought battles in cardiology before. In GUSTO it had been the thrombolytic wars between the TPA and streptokinase forces, and this had been a truly bitter division. But back then the different sides spoke the same language. When it came to COURAGE, it became clear, the common culture had split and divided. The two sides seemed to exist in alternate, mutually exclusive worlds.

The war over COURAGE was fought on multiple battlefronts, nowhere more intensely or publicly than in the media, including the mainstream media, the specialized medical media, and, for the first time, the online medical media, such as TheHeart.Org, where I was the editor at the time.

Something completely unprecedented happened early on. Martin Leon, the single most influential interventional cardiologist in the known universe, was busted for sharing the main result and criticizing the trial at a satellite symposium prior to the embargo lift. Leon had been a reviewer for the NEJM paper and was subsequently sanctioned by both the American College of Cardiology, where the results were presented, and by NEJM. My point here is that neither the trial investigators nor the trial critics were able to control the message.

In recent years this loss of control— by either investigators or critics— has continued to accelerate. For important and potentially controversial trials it is no longer possible to control or even predict the way results are communicated to either the profession or the general public. The investigators may have an intended message but this can now be changed or even hijacked by outsiders, even nonexpert outsiders like myself, using both traditional and social media. (A corollary is that unoriginal or unimportant trials may be completely ignored or, alternately, subject to manipulation by interested parties.)

Let me briefly mention a few studies from the last few years. The PARADIGM trial was almost immediately subject to intense criticism from skeptics on the CardioExchange website. In the space of 24-48 hours the terms and scope of the debate about PARADIGM were established. This swiftly dominated the broader reception of the trial both in the general media and even, to a remarkable degree, the academic discussion of the trial.

I’ve written a lot about SPRINT in the last few years. I just want to make one point here now. The SPRINT investigators forgot it was a new century. They thought they could pull off a GUSTO-type shock and awe campaign and steamroll everyone with their predetermined message. Let’s just say it didn’t work and, in fact, their efforts backfired on them.

More recently the reception of ORBITA shows how this trend continues to accelerate, in this case in dizzying fashion. For good reason most physicians and academics are skeptical or even afraid of Twitter, but in this case if you weren’t on Twitter you missed out on an amazing event: the immediate, overwhelming, and, in general, really high quality discussion about the trial. This discussion included a large number of prominent general and interventional cardiologists and clinical trialists engaged in furious debate. They almost immediately identified the topics that will undoubtedly be the main source of discussion about this trial for a long time.

Many of you in this room probably don’t feel comfortable with social media in general and Twitter in particular but you will almost certainly have to recognize its impact. If you want to have any say in the reception of an important or controversial trial you may need to change your tune. The role of social media is evolving and much about it is unclear and unknown, but it is certain that social media has changed the way clinical trials are received.


Speak Your Mind