Informed Consent That Builds Trust, Protection, and Understanding in Clinical Research

Informed consent, or a patient’s formal agreement of understanding to participate in a study, is a critical part of modern clinical research. It has become a collaborative process that enhances the knowledge and autonomy of patients—and enables the success of clinical researchers.

“Informed consent has always been, and will continue to be, a cornerstone of the ethical principles of doing research with human participants,” says Susan Kornetsky, MPH, director of clinical research compliance at Boston Children’s Hospital and one of the leadership faculty at Harvard Medical School’s Foundations of Clinical Research certificate program. “In order to be able to succeed in clinical research, it becomes a major element of trust for individuals to participate.”

The process goes well beyond signing a form. In fact, informed consent is complex and nuanced, but never static. Thus, it is essential for investigators to stay current with best practices and keep them top of mind as they develop clinical studies. 

The Fundamentals of Effective Informed Consent

Informed consent begins as soon as the recruitment process starts—when a researcher begins to gauge a participant’s interest and provides information about a study. “How can we, as best we can, assure that people are comprehending what they need to know to make an informed decision? It’s one thing to explain; however, we also want some assurance that people understand,” says Kornetsky. 

With this in mind, she notes, investigators often use a “talk-back” format. Once they go through a full explanation of the requirements and risks, they will ask a potential subject: What did you take away from this? Do you understand the risks? What are your questions? In that way, informed consent becomes an interaction instead of a lecture. 

From there, says Kornetsky, participants need to be given ample time to make a decision. “If someone wants an extra sample of blood to be used in a lab, that’s not going to require as much information. But it’s still not a good idea to talk to someone the day they’re getting on the gurney to go into the operating room.” 

She encourages investigators, when possible, to introduce space between an initial conversation and a formal agreement. “Introduce consent, then have them go home and talk to their family or doctor before they follow up. Try to build in that openness and transparency.” 

Even after a participant agrees, informed consent continues for the duration of the study. When there is new information that may impact a patient’s willingness to continue—side effects, for example, or details about a drug’s toxicity—an investigator will need to reconnect with the participant. 

“Your participant is your partner in this,” says Kornetsky. “You don’t want to enroll someone who doesn’t have the ability to follow up with you or do the extra visits to a hospital. It’s not just a one-way exchange of information.”

What Researchers Should Keep in Mind About Informed Consent  

Many investigators underestimate the amount of time, work, and follow-up that informed consent will take, notes Kornetsky, even if they are working with research nurses and coordinators. 

She encourages them to view this less as a box to check and more of a dialogue. “I tell investigators that they should provoke questions. Instead of just saying, Here’s the information. Can you sign?, pause and say: Okay, we’ve been through a lot of information. You must have some questions. What are you wondering about now?  Investigators also need to appreciate that participants may have different comprehension levels.”

Participants run the gamut in terms of their individual priorities: from wanting to understand every detail about a study to only caring about the broad topics; from caring very deeply about their privacy to not being as concerned about it. “When you prepare an informed consent, you have to remember that people are different. They’re going to focus on issues that are relevant to them as an individual or as a part of a patient group,” she adds.
In a related way, investigators have to carefully assess the participant’s relative understanding about their own condition and the associated medical procedures. Someone who has just been diagnosed with a disease, for example, will need to learn about the relevant terminology before they may be able to agree to a study. 

“If you’re doing research in a very sick population and tell them that they’re going to have a bronchoscopy, they will understand because they’ve had many of them. If you tell a healthy person you’re suggesting a bronchoscopy, you may need to explain,” Kornetsky says. “We want to simplify things, but we have to consider the population’s familiarity with specific medical terminology.” 

For clinicians who refer their own patients to a study, there is a host of extra considerations to bear in mind, she adds. “You need to help that person understand that this is voluntary; if they say no, they’re still going to be taken care of. That individual is going to trust you already, but you’re asking them to do something above and beyond that is not directly related to their individual care.”

Modern Challenges—and Opportunities—for Better-Informed Consent 

Investigators should prepare for informed consent to continue evolving. Over the past decade, changing best practices in health care—from new requirements for journal publication to changes in federal funding—have forced researchers to update their processes and the types of information included in an informed consent form. 

Additionally, as research has become more complex, obtaining informed consent has similarly become more complicated. “In cutting-edge new technologies like gene therapy, there are probably no less than three or four discussions that happen before you actually go into an informed consent process,” notes Kornetsky. 

Today, researchers use electronic methods to obtain informed consent, which may be stored in medical records along with actual research procedures. Given the shared nature of electronic health records, it is important to be transparent with participants about the storage of that information. “What I always say about privacy and confidentiality in today’s world is that it’s not about assuring privacy and confidentiality. It’s about explaining the limits,” she says.

Many hospitals, including Boston Children’s Hospital, are working to stay ahead of these developing complexities. They regularly revise their informed consent templates to incorporate all of this information, while also simplifying the language to be more palatable to a lay audience. This work will need to continue as the health care industry evolves.

“We have to do this well, and we have to change with our environment, including the types of research and the types of technology we use,” says Kornetsky. “It’s the same ethical principles, just applied differently.” 

She encourages investigators to lean into the process. “You have to take all the complexities into consideration,” she adds. “It’s always evolving.”