Researchers Fret as Social Media Lift Veil on Drug Trials

Online Chatter Could Unravel Carefully Built Construct of ‘Blind’ Clinical Trials

http://online.wsj.com/articles/researchers-fret-as-social-media-lift-veil-on-drug-trials-1406687404?mod=WSJ_hp_RightTopStories

By

Amy Dockser Marcus

July 29, 2014 10:30 p.m. ET

 

On her first day in a clinical trial for an experimental multiple sclerosis drug, Jeri Burtchell was convinced she was getting the new drug, not the standard therapy that some patients were randomly assigned to receive.

When she bumped into the trial’s lead investigator in the elevator that day, she told him, “I think I know which drug I’m on!” The doctor put up his hands, waving her off. “Don’t tell me!” Ms. Burtchell recalls him blurting. “I can’t know!”

A nurse later explained to her that knowing who was getting what could compromise the research. Even so, Ms. Burtchell went home and recounted the incident to followers of a blog she was writing about the trial. “The mystery medicine is doing its job,” she wrote.

For decades, the clinical trials vital to developing new drugs have followed a central principle: Researchers and patients must both be “blinded” as to who is getting the experimental drug and who a placebo or standard therapy.

If patients know who has the new drug, or learn too much about how others in the trial are faring, this knowledge could influence how they report symptoms and make it hard to tell whether the drug is working. Staying in the dark throughout a trial is a standard held sacrosanct by researchers. But lately, not so much by patients.

On Facebook groups, online forums and blogs, some patients are effectively jeopardizing the blind. In trials for hepatitis C, multiple sclerosis and ALS (Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease), patients have been sharing details of their reactions and trying to figure out whether they are getting the active drug.

Patients also swap tips on how to get accepted into trials, even if they don’t meet all the requirements. Some who are in trials collect and analyze their medical data and others’ to get an early indication of whether a drug will be a success.

Drug makers and researchers are increasingly concerned that online chatter could unravel the carefully built construct of the clinical trial, and perhaps put patients in danger. They worry that patients may drop out if they suspect they aren’t getting the drug being tested, or may report symptoms inaccurately because of the influence or suggestions of others in the trial.

Patients who share too much “could effectively chill a new drug before it ever gets to patients by misinterpreting early signals,” says Craig H. Lipset, head of clinical innovation at Pfizer Inc., who wrote an opinion piece in Nature Medicine in March calling on trial sponsors and regulators to study the effects of social media. “It’s scary.”

Patients, for their part, often say they have the right to talk about their experiences. In life-threatening diseases such as ALS, patients “want, need and deserve to know” how others are doing, says April Moundzouris, a Chattanooga, Tenn., woman whose “April’s ALS Blog” chronicles her experience with an experimental stem-cell treatment. The early-stage research by Neuralstem Inc. isn’t blinded.

Neuralstem Chief Executive I. Richard Garr , a close reader of April’s blog and those of other patients, says the sharing may pose a challenge later on when it comes time for a trial designed to prove efficacy to the Food and Drug Administration. That trial would likely have to be blinded.

A patient who blogs that he or she isn’t feeling well, isn’t improving or has some symptom can sway how other patients report or their willingness to join a trial, Mr. Garr says.

This is just one of the ways the Internet and social media bear on the drug-discovery process. Richard Bedlack, who runs the ALS clinic at Duke University, is involved in a project that asks patients to tweet tips about alternative and off-label treatments that he and other doctors assess to see if they might make promising research candidates.

By contrast, some pharmaceutical companies have tried to avoid using social media so they won’t learn about something that might make clinical analysis of an experiment more challenging or might have to be reported to FDA, according to Joseph Kim, an executive at Irish drug maker Shire PLC.

Says Mr. Garr: “The FDA is going to have to figure out how to accommodate social media.”

A spokeswoman for the FDA says the agency doesn’t have a policy on subjects in trials using social media to communicate with one another.

PatientsLikeMe, a Cambridge, Mass., company that runs a patient network and research platform where patients share health information, including during clinical trials, is wrestling with how to address the effects the constant sharing of information can have on trials.

In a 2012 paper, Paul Wicks of PatientsLikeMe wrote that according to the company’s data, a little more than 400 patients on the site have added treatment information that shows they are on a clinical trial. If patients start trying to determine if they are receiving the new drug, he asked, “how should we respond to this as researchers or as a company?” Dr. Wicks says the company is trying to get patients and researchers to work together to design trials, believing that collaboration will lead to better understanding of the issues.

To date, no clinical trial has been stopped because of online sharing of patients’ experiences. But drug makers are starting to take pre-emptive steps.

Shire helped create educational videos about the consequences of sharing too much, working with a Boston-based nonprofit called the Center for Information and Study on Clinical Research Participation. In one animated video, a blue bean’s description of side effects from a drug causes a yellow bean to drop out of a study. Shire, whose board has agreed to a takeover by AbbVie Inc., tells patients how to download the videos.

“The industry needs to do a lot more,” says Shire’s Mr. Kim, director of patient recruitment and engagement. “It is a hard thing to modify behavior without it being too controlling.”

Vertex Pharmaceuticals Inc. was testing a drug for hepatitis C when Lindsay McNair, then its senior medical director, got an alert from an investigator that patients in the trial were posting about it. She went to MedHelp.org, a site that hosts patient message boards, and started reading. “They were really incredible threads,” she says.

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Dr. McNair discussed the posts with others at the Boston-based company. They were concerned about patients harming their health by not reporting symptoms out of concern they could be taken off the trial. If enough dropped out, it might be hard to get an adequate test of the drug, says Dr. McNair, now chief clinical research officer at WIRB-Copernicus Group, which provides regulatory and ethical reviews of research.

So for its next trial, Vertex added an unusual paragraph to the consent document for subjects, explaining that rumors about side effects or about the drug’s efficacy might affect results and require doing the study over. Participants should feel free to discuss their participation with family, friends and medical providers, the paragraph said, but not publicly such as in Internet message boards.

“It was meant to be informational and educate about the implications discussions could have, but not to say they can’t talk or there would be repercussions if they did,” says Dr. McNair.

Not all the patients understood this. One who signed the document then posted on the MedHelp Hepatitis C forum: “There’s no specific legal recourse spelled out, but there is another section that states that my participation in the study can be ended at any time without my permission.” The patient wrote that the forum provided him with important information about managing his disease and about the trial. “I hope people will still talk to me here?!” he added.

Vertex says oversharing on social media isn’t grounds for eviction from a study. It continues to warn about the problem in consent forms. Vertex says there was no effort to identify or remove from the trial the person who posted on the MedHelp forum.

The hepatitis C drug won FDA approval, and now is sold as Incivek, but “the experience was nerve-racking,” Dr. McNair says.

Dr. Bedlack of Duke says the information patients share online can turn out to be incorrect. Before revealing the drug information at the conclusion of a trial, he often asks patients to guess whether they got active drug. “Most times they don’t get it right,” he says.

Ms. Burtchell, the multiple sclerosis patient, did guess right.

Now a 53-year-old resident of East Palatka, Fla., she was diagnosed in 1999 with the kind of MS that involves relapses interspersed with remission. By 2007 she estimates she had suffered nearly 30 relapses and was so exhausted she had difficulty caring for her young son.

She enrolled in a trial for an experimental therapy from Novartis AG that aimed to be the first pill for the disease, which was treatable only with injectable drugs. The trial matched one of injectable therapy, Avonex, against the experimental oral drug, called fingolimod.

Ms. Burtchell started a blog to chronicle her experience from start to finish. In the post after her first treatment, she told why she believed she was getting fingolimod.

In the past, she had taken injections for her condition. In the trial, she didn’t feel the stinging or pain she remembered from shots—a sign, she believed, that her injection in the trial was a placebo.

Also, after she was given a pill, she noticed a nurse recorded a fall in her blood pressure, which she knew was a potential side effect of the experimental drug.

Nearly three months into the trial, Ms. Burtchell posted that, for the first time since her MS diagnosis, she was able to hop on one foot.

“Maybe it’s the Fingolimod…,” she speculated. “Whatever it is, I feel better every day.”

When information on the study was revealed, it turned out she was indeed getting the experimental drug.

A spokesman for Novartis says consent forms for its trials don’t prohibit patients from talking about their trial participation. The spokesman says the company didn’t interact with Ms. Burtchell during the trial.

The drug was approved by the FDA in 2010 and now is sold as Gilenya. Novartis continued to study it in nonblinded research, in which Ms. Burtchell participated. Eventually, she served for a time as a paid speaker for Novartis, sharing her experiences.

She also continued to blog.

One of her followers was Pfizer’s Mr. Lipset, who was interested in how patients use social media.

In September 2011, he sent her a message on Twitter asking to talk. Mr. Lipset says he wanted to discuss the downsides of patients comparing notes. They talked, and each saw the other’s side.

Mr. Lipset says Ms. Burtchell helped him realize that “it’s not the patients who will change, but the researchers who have to change.” She reminded him, he says, that “ultimately patients are human beings. They are going to talk.”

In Ms. Burtchell’s post after their talk, she conceded that the Pfizer executive had made many good points. Even so, she concluded, “If I’m going to be poked and prodded, I’m going to be here blabbing about it.”

Later, her views started to shift. In 2012, Mr. Lipset invited her to appear on stage with him at a pharmaceutical-industry conference in Boston. She was asked if she ever worried about influencing others in a trial. “I think that is when the realization of what I had done really hit me,” she says.

At a February drug-industry conference in Miami where she was asked to speak about patients and social media, Ms. Burtchell proposed her own solution: that drug companies create online forums where patients can get practical questions answered by investigators and can commiserate with other patients about social issues in a moderated setting. She set up Partners in Research, a website that guides patients through the clinical-trials process.

She continues to take Gilenya for her MS and has had two relapses while on it, most recently in February. She is part of a study looking at its long-term effects.

But she has stopped her blog.

“I’m too aware of the impact,” she says, “too conscious of my audience, to blog like that again.”