In 2006, Johnson & Johnson got hit with a frying pan to the face when the BBC ran an interview with a man involved in a J&J trial on the anti-psychotic Respiradil. The study subject had bipolar disorder, and was told by his doctor that the drug he had been taking was suddenly discontinued and he needed to start taking Respiradil instead. The man had no idea he was participating in a clinical trial. Hmmmm.

J&J's Emily Walker, associate director and global trial manager for global clinical operations, played the BBC clip in a session on informed consent at the 45th annual Drug Information Association (DIA) conference last month. Then she told the crowd how her company responded: It formed a team to examine what needed to change on its standard informed consent form (ICF).

It could be a lot. Walker explained that the company quickly did a survey using random people on the street in Atlanta, Philadelphia and New York City. Most of the key points in the company's ICF were lost on the average citizen. Even though each participant spent 30 to 40 minutes going over the forms, their readability was deemed low, as was the survey participants' comprehension and retention of the material.

Problematic Protocol

Surprisingly, there were consistent and significant misunderstandings of the trial protocol. Walker played audio of some of the survey participants' answers. After reading about the purpose of a diabetes study—to compare drug A with drug B for controlling diabetes—participants were asked what the point of the study was. One person said, “I think it would just be to determine if you could have diabetes and how bad it was.” That was typical of the answers the team was getting.

In response, J&J decided to use bold type to accentuate passages of special importance on the ICF—for instance, where it explains what the study is attempting to accomplish. Says Walker, "We know that paragraph after paragraph of text causes even the most interested party to feel overloaded, glaze over and lose focus—especially so if one is not familiar with how clinical trials work in the first place."

So Random

Participants also had a particularly hard time understanding randomization. “It's not intuitive to the lay person who's not familiar with trial design,” says Walker. In response, J&J pulled randomization out into its own section and explained it in stand-alone fashion, not burying it within a long document where it could get lost.

“Double blind” was also misunderstood far more than it was understood. Walker played audio of an interviewer asking a survey participant whether or not her doctor would know which drug she was taking during the study. She responded, “I think my doctor will probably know which drug I'm on.” Says Walker, “In their minds, they think somebody should know, somebody has to know what treatment I'm on.” J&J decided that term required extra explanation.

Parentheses Needed

Nor did people understand the concept of a paper diary. Men had an especially hard time (some thought it meant "chart"). Take away for J&J? After such terms, include a short explanation in parentheses, as in paper diary (a journal or notebook). “Explain those terms—even the simplest terms,” says Walker. “Really, we have the responsibility to do so.”

The study protocol that J&J was using for the survey didn't involve a placebo, yet in the risk section there was an explanation of placebos. That tripped up participants. The take away was two-fold: Placebo is an unknown concept to those outside the scientific world and needs extra explanation. And if the study in question does not involve a placebo, remove the explanation of it from the ICF.

“You've got to keep info in there that has meaning to the patient,” says Walker. “We may have a habit of pulling directly from the protocol, the information that's for scientists or physicians, and to the patient it means nothing. What has meaning to the patient?” Focus on that, and remove everything else, advises Walker.

Confusing Stats

Another area of concern was the explanation of possible side effects. Survey participants didn't understand the numbers as presented. For example, an interviewer read this sentence to the study participants: “Lactic acidosis occurs in one out of 30,000 patients and is fatal in 50 percent of cases.” Walker played audio from one man who said, “To tell you the truth, to me that doesn't make much sense.” That was a fairly typical response.

“Statistics is a very complex topic,” says Walker, adding that the participants focused on the 50 percent fatality part, but didn't absorb the one in 30,000 part, which indicates that the side effect is rare. The lesson is that sites may have a role to play. “You need to let sites know they need to spend some time explaining,” Walker says.

Bullet Points

J&J now includes a bullet-pointed summary review of the key points in its ICF. It's a handy sheet of paper that a potential participant can easily understand. It's simple, with lots of white space, says Walker. The current challenge, she says, is that protocols are getting more complicated at the same time that regulators want shorter ICFs—just four to five pages. In that environment, it's a feat to make an ICF comprehensive, user-friendly and readily intelligble. But it can be done.

Walker didn't say how widely the new ICF guidelines are being adopted throughout J&J. But the company continues to explore ways to deliver ICF information to potential trial subjects in a way that guarantees that they understand it. J&J is experimenting with a magazine-type layout with colorful design and pictures to illustrate key points. Other sponsors, says Walker, are looking at using video and quizzes to make sure the details of the ICF have been understood.

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