What do clinical trial participants want?

Collaboration with participant is key

Researchers increasingly are told they need to involve participants in clinical trial design, but most would agree this is a difficult ideal to follow.

For one thing, it's hard to find people who are willing to imagine and talk about what they would do with regards to research if they had cancer or some other potentially deadly disease.

"The reality is many people are first faced with the notion of a clinical trial once they are diagnosed, so our conversations often start at a time of great emotional turmoil," says Lidia Schapira, MD, an oncologist at Massachusetts General Hospital in Boston. Schapira speaks at national research conferences about respecting research subjects.

However, what can be achieved is collaboration between researchers and study participants in which the discussion of a clinical trial is a conversation and not a one-sided recitation of the informed consent document, Schapira says.

"The collaboration has to be around the possibility of this particular person, who is diagnosed with an illness, entering the study, with the expectation that he or she will gain something from it," Schapira says. "And we should share the uncertainty if the outcome of the trial is uncertain."

Perhaps a turning point in how the research industry collaborated with the community and potential subjects was reached in the last 25 years of the HIV/AIDS epidemic.

"Our experience in AIDS has taught research a lot," says A. Cornelius Baker, a community health advocate and former executive director of both the National Association of People with AIDS and the Whitman Walker Clinic in Washington, DC.

"We've learned we can grant access to study drugs to people in need of treatment prior to the drugs being approved," Baker says. "As a result of that, I think we've created a much more humane drug approval process."

Early access and compassionate use of drugs also have resulted in greater respect for the pharmaceutical industry and scientists among AIDS advocates and others impacted by the disease, Baker notes.

"People don't see it as just about the pharmaceutical companies and science using them as guinea pigs and not being in a partnership," he adds.

Nonetheless, that trust still has to be built in other communities, and one way clinical trial sites can achieve this is through transparency, Baker says. Secrecy about trials leads to mistrust, particularly when a problem occurs and its public disclosure comes in the form of a media event, Baker explains.

Investigators and clinical trial professionals can improve transparency and build trust through consistent communication with participants, Baker and Schapira say.

For example, they can demonstrate respect for participants through education and even more casual conversations with them, Schapira says.

"We have at the cancer center a series of lectures that are offered to all patients and people with them," Schapira says. "Some of these are general lectures about research, and we try to orient people by explaining how cancer clinical trials advance from ideas in a laboratory to being tested and offered in public."

The educational sessions also discuss the various phases of clinical trials and the safeguards put in place to protect participants, she adds.

AIDS advocates worked on public education and treatment education very early in the epidemic's history, Baker notes. "With John James' [book] AIDS Treatment News and [newsletter] AIDS Alert, and the Project Inform work, we've had a number of different environments in which to learn about the science being created to treat HIV infection," Baker says.

Also, when the pharmaceutical industry and academic research institutions ran into problems regarding public perception, they began to invite treatment advocates and educators to seminars where they could be educated about the latest science and research so these people could, in turn, educate the communities they represented, Baker explains. "That developed greater trust and greater transparency," Baker says. "It also created a partnership so people with HIV could see the research being conducted as in their interest."

Since they see research as something that benefits them and since they see researchers as people who listen to their concerns, HIV-infected people are much more willing to participate in research, Baker adds.

It's a misperception to think people don't want to participate in clinical trials, Baker says.

But the problem is that a few well-known examples of blatant ethical violations in clinical research have made it difficult for some people to trust researchers, he says.

The only way to resolve these fears and concerns is to be totally open and transparent during the research process, to hold to high ethical standards, and to directly involve the community, Baker says.

Baker and Schapira suggest these strategies for building trust among potential subjects:

1. Hire a patient advocate.

Research institutions should have a patient advocate whose role is to be the voice of the patient or participant from the recruitment stage on, Baker says.

The patient advocate's role also could include helping the clinical trial site ask and answer these questions:

— How do we recruit people?

— How do we educate people who are in the trial?

— What is the benefit of the trial?

— How do we educate people in the larger community?

"As a result, you build the capacity to truly be engaged with the community," Schapira says. "It's the importance of representing those who are participating in research and those who will be impacted by the research."

2. Develop better educational strategies.

There are many Web sites and written material available about clinical trials, particularly when it comes to cancer and HIV.

Schapira recommends sharing with patients a video that was designed to answer many of their questions. It's called "Entering a Clinical Trial — Is it Right for You?" and it can be downloaded for free off the web site of the Dana-Farber Cancer Institute of Boston, MA at http://www.dana-farber.org/res/clinical/trials-info/.

Also, the National Cancer Institute has many publications and videos about clinical trials, which can be found online at www.cancer.gov.

Research sites need to build up the scientific literacy of communities to help people understand how difficult it is to develop drugs and how the process includes a lot of dead ends, but the only way to learn what works is to keep at it, Baker suggests.

It's important to inform the larger community about research projects, and this doesn't mean just issuing press releases when the news is good, Baker says. For example, when a proposed drug is found to have some safety concerns, it's important to let the public know about these findings and to explain why a trial has been discontinued, if that was the result of the concerns, Baker says.

When a company has been upfront about the study all along, people will accept the bad news and move on; it won't become a media sensation or scandal, Baker adds.

"We do not yet do a very good job of explaining to the community or public at large when a trial does not succeed and what we learned from it," Baker says. "When we only publish the good news and hide the bad news, people believe there's more bad news out there, so they don't trust everything about the drug or treatment."

3. Make clinical trials inclusive.

One of the problems with clinical trials and the public perception of research is that often trials are too exclusionary, Baker says.

Some research institutions and sponsors only want what they consider the best population and this often ends up being white men, Baker says.

"The real world includes women who can get pregnant, people who are not white, people who use drugs," Baker says.

People are more likely to trust research when trials include participants who look like themselves, he adds.

"Given the demographics of the HIV epidemic, it would be horrendous for a trial to not look like all of the people who are infected," Baker says.

"You don't want to have a situation where black people will look at a new drug and say, 'We don't know if that drug will work with us — that drug isn't for us,'" Baker adds.

"I think we still have challenges to having truly inclusive clinical trials," Baker explains. "Even diseases that impact heavily on minority populations, like hepatitis and HIV, still have treatment trials that are not representative enough, and I think that's not acceptable."

4. Respect clinical trial participants through words and action.

Respect for participants is a flexible goal that must be adapted to different scenarios, but it also must be a part of every single conversation within a medical clinic, whether it's about the research or clinical care, Schapira says.

Clinical trial professionals and physician investigators should promote the real spirit of research in which there's a sense of shared responsibility for the research enterprise, she adds.

"The patient and possible research subject would, hopefully, feel some excitement about participating in a trial," Schapira says. "The patient would be reassured that he or she would be ethically offered either the best-known treatment or something that might be better."

A clinician's bedside manner can be learned and improved, and that's an aspect of clinical trial research that could be improved, Schapira says.

People feel at ease with physicians who listen to them respectfully, elicit their concerns, present information fairly, and who respond to them with empathy and other appropriate emotions, Schapira says.

"All of those things are teachable skills, and we do have packets, seminars, workshops, and classes where we teach nurses, physicians, and nurse practitioners to do this well," Schapira says. "We teach them to really form respectful relationships and how to communicate in clear ways."

5. Work on the consent process.

Consent forms need to be more user-friendly, including shorter versions which are easier for patients to read, Schapira says.

"These are for patients who don't have the patience or educational level to read through a consent form, but who still deserve to know what they are signing up for," Schapira says. "We also need better language, especially when talking about randomization, and we need better training in how to have these conversations with patients."

One suggestion is to have the researchers who do very well with informed consent videotape their process and share it with colleagues, Schapira says. "Or they could have workshops to help new researchers improve their skills," she adds.

A simple way to improve the informed consent process is to build-in extra time, Schapira suggests. "I always give the informed consent form to the patient and ask them to take it home and read it and to not sign it until they've thought about it for at least a day or two," Schapira says. "You need to give them time to process the ideas and concepts."