"The FDA, the Belmont Report, and Nuremberg Code all speak of the feasibility of comprehension testing," said Hochhauser. "But what's a passing grade? If it's 70 and the grade gets posted in patients' medical records, can that score later be used to support an injury claim based on inadequate understanding of the protocol? Should retesting be done on would-be participants whose score falls below a certain threshold?" he said.

Improving the informed consent process once a trial concludes may be the most difficult task of all. Even study results published in mass media reports aren't particularly useful to participants. Due to highly technical—often incomprehensible—titles on consent forms, participants often have no way of knowing if the results referred to in a published report came from the same study that they participated in.

Clinical research professionals can help by directly sharing study results with participants. But simply sending them a difficult-to-read article from the Journal of the American Medical Association or New England Journal of Medicine is unlikely to clear up the confusion. At a minimum, care and time must be taken in communicating study results with the volunteers who gave the gift of their participation. There's no question that this step will add costs to the study budget. The return on such an investment, however, is likely invaluable, as it builds stronger relationships with people who are familiar with the clinical research enterprise and who can serve as ambassadors for public outreach and education.

Some investigative sites are independently doing what they can to improve the situation. At Clinical Research Atlanta, for example, Clinical Operations Director Michelle Sowell tries to get consent forms in the hands of prospective enrollees days before they step foot in the clinic. Some sponsors worry that sending out consent documents in advance will scare people and discourage participation, but she believes it gives people an opportunity to highlight sections that concern or confound them and write questions in the margins so they can make a truly informed decision. "Subject comprehension of study protocols has noticeably improved since the site started mailing out consent documents three years ago," Sowell said. "It has also cut down on screen failures."

"It helps that the clinic requires study coordinators to read, initial, and date the portion of the investigator's brochure dealing with adverse and serious adverse events," added Medical Director Nathan Segall, MD. "If they're asked a question, they either know the answer or know where to look it up."

At the initial screening visit, coordinators carefully review with subjects the purpose of the study and what to expect at each visit as well as clear up any misunderstandings they have about compensation, says Sowell. "Questions are heavily encouraged and if comprehension is still a problem, those people simply don't get enrolled. For pediatric trials, children who express worries about blood draws or injections also don't get enrolled—no matter how enthusiastic their parents might be. At every study visit, coordinators go over what to expect moving forward and remind participants of their volunteer status," she said.

"Whether it is months or years between the final study visit and when the trial is unblinded, participants are always told if they were on an active compound or a placebo," said Segall. "That can be medically important information to someone with a ragweed allergy who received an active immunotherapy injection. When actual study results would be of value to participants, the site passes on whatever it learns from sponsors despite the cost and logistical difficulties of doing so."

At Pivotal Research Centers in Peoria, AZ, "Coordinators will sometimes spend an hour with prospective study subjects completely reading through consent forms out loud to ensure the information gets properly digested," explained Clinical Research Coordinator Laura Vigliotti. "Coordinators might also highlight certain sections, such as duration of the trial and possible side effects, which tend to be decisive enrollment factors."