NeuroVoices: Paul Ford, PhD, on Ethical Balance in Complex Clinical Research for Neurology

Paul Ford, PhD

(Credit: Cleveland FES Center)

At Cleveland Clinic’s Neurological Institute, ethics are integrated into both clinical care and research, with an emphasis on providing patients opportunities to participate in innovative studies. The Neuroethics Program, directed by Paul Ford, PhD, focuses on addressing ethical considerations in the treatment of neurological diseases, particularly in relation to neurosurgical interventions. Ford’s work includes qualitative research on ethical practices in neurology and oversight of an ethics core that assists researchers in incorporating ethical frameworks into grant proposals and study protocols.

With more than 2500 ethics consultations spanning inpatient, outpatient, and research contexts, Ford has engaged with a range of perspectives from patients, research participants, families, and health care teams. These experiences have informed his approach to navigating complex decisions and identifying strategies that balance scientific objectives with patient well-being. His work frequently involves collaboration with multidisciplinary teams to guide ethical decision-making in both clinical and research environments.

In a new iteration of NeuroVoices, Ford emphasized the importance of ongoing ethics training for clinicians and researchers, particularly in the context of complex neurological interventions. He noted that considerations such as study design, informed consent, risk-benefit assessment, and cultural context can contribute to safer and more equitable research. Proactive safeguards, inclusive participant selection, and consistent communication were highlighted as key elements by Ford for ensuring that research advances align with the goals of both scientific progress and respect for participant dignity.

NeurologyLive: How does embedding ethics into day-to-day clinical care and research at the Neurological Institute influence decision-making?

Paul Ford, PhD: Over the last 30 years, there has been increased attention to making sure we have ethics training for clinicians, researchers, and clinician-researchers. We create a sort of floor of expectation for the skills you have and the understanding of regulation, the importance of institutional review boards (IRBs) or data safety and monitoring boards (DSMBs), and the roles they play. It's really nice being integrated, where you have a nice floor that everyone has a common understanding of them.

When we enter the incredibly complex, messy world of clinical care and clinical research, where people are both patient and research participant, we now have the tools that we can enhance for the really complicated cases. It’s really a way to have me involved with tough decisions that are the common ones, because my clinician colleagues guide patients and support shared decision-making beautifully. But with complicated technologies and complicated situations, they need new skills.

I help people develop new skills for thinking these through. Those people include patients, their families and networks, potential research participants, doctors, nurses, nurse practitioners, and research coordinators—all who can, as they have these complex conversations, do them better, more respectfully, and in ways that enhance what we all really want which is to improve people's health and thriving. We do this through improving scientific knowledge.

Cancer research, very early on, had a mantra that everyone should be part of research trials, especially in pediatric cancer, and they have made great leaps and bounds. But what they meant was not just that everyone should be in a trial with a dangerous drug or surgery, but that everyone should contribute their data so that we know how to do things better in the future.

The Neurological Institute, for 20 years, has been deeply committed to having me collaborate and be a partner—not as an outside police—in developing their research, supporting their researchers, helping multidisciplinary teams select patients for complex surgeries, and meeting with patients and sometimes research participants to help with complex decisions. It’s about creating a safeguard to ensure we're doing the right thing for people.

What are some of the common ethical dilemmas in research, and how do you help clinicians and researchers navigate them?

There’s really an opportunity to reflect further on ethics at each stage of the conversation. When you go to design the protocol, there are lots of really interesting choices that you have to make, particularly for surgical interventions such as devices like brain stimulators, whether deep brain stimulation, cortical stimulation, or vagus nerve stimulators.

There are various ways you can study these. Traditionally now, with most of these technologies, we don’t support a true placebo-controlled, double-blind surgery. Often, a crossover design is thought to be more ethically appropriate than implanting an inert device that could never help a patient. That would put the patient at too much risk with no potential for benefit.

So, you ask: should there be a washout period? What does a placebo mean in a crossover design—single crossover, double crossover? What are the rescue opportunities during a washout phase? In pain research, for example, we thought a lot about what happens during that washout phase. If someone has terrible pain, they shouldn’t have to suffer unnecessarily. Similarly, with movement disorders, you don’t want someone to become completely debilitated suddenly. You need safeguards and have thought ahead, what are the potential ways in which this could change things?

Very early on, I was part of a DSMB for a study in minimally conscious individuals using deep brain stimulation. The question arose that if a person is emerging further out of the minimally conscious state when the device is on, but you turn it off, and they sink back into a lower state of consciousness, is it ethical to take that away—even briefly—if you don’t know you can restore it? After that study, we made sure to address that point more explicitly in the consent process.

There are these ways of doing things and structuring the consent process that are important. We also need to be careful about unfair exclusions. Sometimes protocols exclude anyone with psychiatric illness. There may be reasons to exclude certain conditions, but not all, so broad exclusions can be problematic.

Another concern is off-target effects. The brain works through circuits, and these often run through areas like the basal ganglia. Even if the goal is to control hand tremor, you must watch for effects on depression, attention, or sleep. I recall a neurosurgical meeting where someone pointed out that stimulating a certain part of the brain could disrupt sleep—a devastating effect that isn’t always considered. Keeping researchers attentive, even if it's not your primary outcome, of these off-target effects, are pretty important.

It’s about balancing risks and benefits. Sometimes it’s not ethically appropriate to offer a set of risks to a patient or research participant. I’m not a “no” person, but I am a “let’s do it the right way” person. There may be several right ways, depending on your objectives, but it must be done with rigor. That’s the first phase.

The second phase is when research is up, and running and unexpected situations arise. For example, a patient in awake surgery may say, “Stop, I don’t want to do this anymore.” Maybe the clinical procedure is standard care, like deep brain stimulation for a patient with Parkinson, but you’ve added research mapping. The standard for withdrawing from research is different from withdrawing from clinical care. In real time, we have to think: do we stop everything, or just some things? What’s in the best interest of the patient-participant who’s going to benefit.

Participants of trials should also be compensated when research involves extra risk or burden—not as inducement, but as a form of respect. I’ve also advocated for participants to share their experiences with the research. At the end of a trial, questions about consent can arise again. Even if at the start of a trial someone agreed to have a device explanted, it’s still their body. They still retain bodily integrity. You still need to have consent, but you need to anticipate what it would mean to have a device in good respect.

Was there anything else you wanted to say as a closing remark on ethics in clinical care and research?

I’ve been privileged to develop strong working relationships with colleagues in neurology, neurosurgery, and neuroscience. I really like the attitude of one of our researchers, Andre Machado, MD, PhD, of Cleveland Clinic, where I was a consent monitor for a very innovative deep brain stimulation trial as an extra safeguard for those patients. After I spoke with one participant post consent, I realized they didn’t fully appreciate what it would mean for their life. I told Machado, and instead of being upset, he thanked me for helping him avoid a “near miss.” Enrolling someone with mismatched expectations only causes problems later because they're not going to be engaged, they're going to be disappointed, potentially drop out.

In another case, a patient’s language and cultural expressions were misunderstood by the team as a lack of motivation. When I explored further, I realized she understood the uncertainty of science perfectly and was expressing her community’s hope. That meant she should not be excluded.

Sometimes I say no, sometimes I say you shouldn’t say no—it’s all about communication. The best work I do is helping develop new skills for clinicians, researchers, and patients: communication, identifying what’s truly at stake, offering alternative strategies, and taking the other person’s perspective. To me, ethics is about balancing what’s important when you have to sacrifice something else of importance—knowing what you’ll preserve and what you’re willing to risk.

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