My message: Ask the hard questions.

The Association of Health Care Journalists annual conference (#ahcj13) covered a variety of topics, with lectures and panels followed by question and answer sessions. As with many conferences, it was tough to choose between competing sessions. I learned a great deal about health care, databases, and resources to help make accurately tracking data more efficient. I was glad to see several sessions covering medical reporting, particularly “Covering Medical Studies: How Not to Get It Wrong.

As a clinical researcher, I was, as might be expected, particularly interested in the session moderated by NPR’s Scott Hensley:

What you need to know about clinical studies but were afraid to ask

I appreciated the panelist’s comments, but was frustrated that the underlying message addressed only the more positive aspects of clinical trials. Mind you, I have been generally pro-trials in my practice and my writing, but have become a bit more skeptical in recent years. I thought AHCJ was to help teach journalists and bloggers to ask the hard questions and to dig. This session, while informative, failed to do so.

Dr. Jeffrey Drazen, editor in chief of the New England Journal of Medicine, gave a largely historical perspective, focusing on the first randomized trials to treat TB in 1931. He then fast-forwarded to the 1960s and the advent of large clinical trials and the need to improve patient safety measures for trials. I agree with Drazen that the Data Safety Monitoring Boards (DSMB) have a very valuable role in protecting patients, by overseeing the progress of clinical trials and evaluating interim data at specific endpoints, thus allowing a trial to continue, if results are not yet definitive or stopping a trial prematurely. Sometimes premature discontinuation happens because of safety concerns. Other times, a study might be stopped prematurely because trial results are so strong that the DSMB believes it would be unethical to continue enrolling more subjects (efficacy) or, conversely, for futility (the trial will never achieve statistical significance). The DSMB comes in relatively late in a trial, however—and as Drazen noted in 2010, the DSMB has sometimes been manipulated by the sponsor pharmaceutical company. Is it any wonder then that physicians are less likely to trust results labeled as coming from a pharma-sponsored study? (Unfortunately, physicians also tend to overlook the incentives or conflicts of interest NIH investigators have to get a prestigious publication).

James H. Ware, Ph.D., Professor of biostatistics and associate dean for clinical and translational science, Harvard School of Public Health raised some advantages for adaptive clinical trials and for accelerated approvals based on surrogate markers.

I would caution journalists much more strongly than Ware did to look at how strong the evidence is to support use of a surrogate marker. For example, at an earlier panel, Dr. Jerry Avorn, Professor of Medicine at Harvard Medical School and Chief of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital, noted that a new drug to treat multidrug-resistant tuberculosis (MDR-TB), bedaquiline (Sirturo), had received “fast-track” approval by the FDA, based on a surrogate marker, yet was associated with a 5-fold increase in deaths. Post-marketing study results are not required until 2022, and may well not be completed.

This issue of relying on surrogate markers, when we really may not have a good understanding of what they represent, is in the forefront again this week as the FDA is recommending use of surrogates be allowed to enable earlier treatment of patients for Alzheimer’s—before there is actual concrete data as to safety and effectiveness. While companies would be expected to do post-approval studies confirming the value of their drugs in real life scenarios, in fact their history of completing post-marketing studies is abysmal, and there appears to be little accountability.

One speaker blew everyone away—Linnea Duff, with her compelling story of her participation in a Phase 1 (first in human) clinical trial and battles with lung cancer. Linnea is an incredibly powerful advocate for participation in clinical trials, noting that doing so has enabled her not only to help herself but to provide a meaningful contribution to others. She has lived eight years now since diagnosis of non-smoker’s lung cancer, when there is an expected 5 year survival rate of only 15%. . .yet she notes, “I am an outlier.” She concluded, “I start every day with three simple words: I Am Alive.”

Ron Winslow, deputy bureau chief, health and science, The Wall Street Journal, had the unenviable position of following Duff’s moving talk. He observed that the number of retracted trials has gone up 10-fold in past decade – and cautioned that it is important to consider reliability and reproducibility when reporting trial results. He also soundly noted, “We don't cover failed trials enough,” nor often put them in the context of an unmet need.

Unfortunately, due to time constraints, I was unable to provide the feedback I had hoped to in the Q&A. So, as promised there, here are more of the comments and questions for the #ahcj13 panelists on clinical trials that I had hoped to make.

Journalists (and critical readers) if you want to present your audience with a more accurate assessment of a clinical trial, you need to be asking probing questions including:

1) Why is this trial being done? What question does it ask—and does that appear to be an important scientific question? Or is this more a marketing ploy to extend the indications for the drug? (e.g., another look-alike drug for erectile dysfunction, or the use of anti-psychotics like Seroquel for treating public speaking anxiety. [This trial, like the series I have been writing about on the Dan Markingson suicide on a psychiatric clinical trial, was conducted at the University of Minnesota.]

2) What phase of a trial is this? Phase 1, first in human? Or post-marketing?

3) Are the risks of the drug proportionate to the illness being studied? For example, a volunteer for a trial for metastatic cancer might well be willing to accept more risks—and should likely be allowed to—than someone who has a relatively minor problem, especially if drugs with good safety profiles are already available.

4) What was the make-up of the Institutional Review Board that approved the trial? Did they have the scientific depth or expertise to really understand (this is getting harder and harder as many studies require expert knowledge in an area)?

5) What are the conflicts of interest of the IRB and its members? (Other than being paid by the study sponsor for their review and approval). What is their stance about patient protection? (See Alice Dreger's "The Worst of All Possible IRB Worlds" and statements like that of Moira Keane, the former head of the UMN's IRB, who stated that the IRB is not responsible for protecting clinical trial subjects.)

6) Read the informed consent. If you can’t understand it, most participants won’t either. What safeguards are in place?

7) If the study is being done at a university, what is the message from the university leadership? For example, I’ve been covering the death of a clinical trial participant, Dan Markingson, at the University of Minnesota, and the allegations of research misconduct. Many ethical concerns have been raised by that, and other trials done by the Department of Psychiatry there. Yet the UMN’s President Kaler recently delivered an address urging reduction in barriers to trials, and encouraging academic-industry trials.

I encourage everyone to ask these hard questions about clinical trials, as I have done with my series about the UMN. I will continue to encourage participation on meaningful trials where there are strong participant protections. And above all, I applaud Linnea Duff’s gift of participation and spirit.


Recommended reading:

Linnea Duff: Clinical trials: My next good chance and

life and breath: outliving lung cancer (for the terminally optimistic)

Previous posts in my series, A Clinical Trial and Suicide Leave Many Questions:

Part 1: Consent?

Part 2: Investigator Responsibilities

Part 3: Conflict of Interest

Part 4: The University of Minnesota’s Response

Part 5: The Case of the Mysteriously Appearing Documents



"Molecules to Medicine" banner © Michelle Banks

Linnea Duff at ahcj13 - courtesy Ivan Oransky/Retraction Watch

Linnea Duff portrait - courtesy Linnea Duff

Dan Markingson photo - courtesy Mary Weiss

pharma cartoon - xkcd