On Tech & Vision Podcast
Balancing Innovation and Ethics: Who is Protecting the Early Adopters?
On Tech and Vision Podcast with Dr. Cal Roberts
Innovations in implant technology are advancing at lightning speed, profoundly impacting the lives of people who are blind or visually impaired. In ON TECH AND VISION, we’ve profiled some amazing new implant technologies that have the potential to restore people’s sight. But in this episode we pump the breaks — because we need to address a critical part of the innovation process: the ethical frameworks that protect participants in early clinical trials. Discussions between doctors and participants in clinical trials almost always focus on the new technology and very rarely on the manufacturer who sponsors the clinical trial — and almost never on the long-term commitment of the company sponsoring the technology or that company’s financial viability. And while clinical trial informed consent includes whose responsibility it is to remove the implants should they fail during the trial, that responsibility usually ends once the trial is over. At that stage, who will maintain or remove the implants that are still housed in patients’ bodies? In this conversation, we use as our example the Argus II, which we featured in the first season of ON TECH AND VISION. The Argus II is a microchip implanted under the retina that, in combination with a special headset, provided some vision to people who otherwise had none. And while the technology was exciting, the company discontinued the retinal implant three years ago, and the Argus II was eventually sold to another pharmaceutical company. Dr. Joseph Fins, Professor of Medical Ethics and Professor of Medicine at Weill Cornell Medical Center in New York, joined us to share his thoughts on today’s big idea: How do we balance the life-changing potential of electroceutical implant technology with the ethics of caring for early participants — particularly after clinical trials are over?
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Roberts: Stop. In On Tech & Vision, we profiled some amazing new technologies, including implants that have the potential to change the lives of people who are visually impaired. Perhaps even restore sight. And with every success of an implant technology, the possibilities only grow. And it is exciting. Innovations in implant technology are advancing at lightning speed and are profoundly impacting the lives of people who are blind of visually impaired.
But, on this episode, we put on the brakes. Because there’s a critical part of the innovation process that needs to be addressed. The ethical frameworks that protect participants in early clinical trials.
When a doctor develops a new technology, there’s a sense of excitement. Doctors share their excitement with patients who do their own research, but mostly rely on the doctor to explain the risks and potential benefits of participating in a clinical trial of something very new.
So, these discussions are almost always about the technology and very rarely about the manufacturer who is the sponsor of the clinical trial. And almost never is there a discussion about the long-term commitment of the company sponsoring the technology or about the long-term financial viability of the company.
And, while clinical trial informed consent includes whose responsibility it is to remove the implants should they fail during the trial – that responsibility usually ends ones the trial is over. At that stage, who will maintain, or remove if needed, the implants that are still housed in patients’ bodies.
So, I want to use as an example for our discussion today a retinal implant called the Argus II that we featured in the first season of On Tech & Vision. Hopefully our listeners recall that this was a microchip that the retinal surgeon implanted under the retina and in combination with a special headset provided some vision to people who otherwise had known. And while the technology was exciting, the company was not successful financially. The company discontinued the retinal implant three years ago, the stock price plummeted and the Argus II was eventually sold to another pharmaceutical company.
Today’s big idea is, how do we balance the life-changing potential of electronic implant technology with the ethics of caring for early participants, particularly after clinical trials are over?
Our guest today is Dr. Joseph Fins. Dr. Fins is professor of Medical Ethics and professor of Medicine at Weil Cornell Medical Center here in New York. Joe, welcome to On Tech & Vision.
Fins: It’s good to be here, Cal.
Roberts: I asked Dr. Fins to join me today to discuss the ethical issues of human experimentation with technology and what happens when implant technology becomes obsolete or when the sponsoring company stops supporting the technology. So, let’s get started.
Dr. Fins, walk us through that doctor-patient relationship when we’re talking about implant technology.
Fins: It’s not necessarily a doctor-patient relationship anymore. It’s really an investigator-subject relationship. that subject may have been a patient of the doctor whose doing this research. There may be role conflicts. When you’re a doctor taking care of a patient and you’re providing routine medical care, everybody’s interests align in a very normal way. when you’re an investigator and you’re exciting about discovering something and becoming famous or making a lot of money because you have an economic interesting in your company that you developed, you have what we call a conflict of interest.
Now, those kinds of conflicts do have to be disclosed. And, you’re presumed to have a conflict of interest until you rebut its potential for distorting or see results. And there have been studies Cal, as you know, where people who have conflicts of interest may not be as pristine in their interpretation of the data as somebody who doesn’t have a conflict of interest.
The first point we have to appreciate is there are role conflicts, and patients may be subjects and doctors may be investigators, and those things may not always align. So, the relationship is regulated in a different way. We have a thing called institutional review boards, which came out of the National Research Act of 1974. This is an independent body in your medical school or where you’re doing research. And, this is where you’re reviewed by your peers and by community members as well.
They look at the research protocol. Does it make sense scientifically? Is the informed consent document clear? Are the scientific predicates adequate to proceed and to do the research? Are the risks disclosed? Et cetera.
The problem is, some of the issues that are specific to devices are not as well articulated as if you were to say in a drug trial. You’re in a drug trial, you get the drug. X, Y or Z can happen. You don’t get the drug; it doesn’t have an enduring impact on you. Of course, there are drugs like thalidomide where there are enduring impacts. But it’s not quite the same thing of having an in-dwelling device in our head or in your eye or something like that.
So, I think there has not been as much focus on the implications of having in-dwelling device for the long-term. This is something I’ve been very interested in. Not in the context of retinal implants, but in the context of deep brain stimulators for neuro-psychiatric conditions. I think there a lot of analogies.
Your implant, if you have an implant, in-dwelling device, is related to the financial health of the company that is sponsoring that. And, as you know, there have been some pretty catastrophic abandonments of people who have these devices. There’s an ethical principle of non-abandonment. And people who are left with these devices that are in-dwelling without ongoing care and the assumption of responsibility in a sense are victims of abandonment. And it’s a really big, pressing problem.
I was at a meeting just a few weeks ago at the NIH, a virtual meeting, on post-trial obligations, and we were talking about these issues. Who was responsible? Personally, I think it’s a tri-partied, at least, responsibility. If people are getting benefits and it’s therapeutic, their insurance should cover it. The sponsoring company should cover it. The medical school should have some role. The government should have a role in paying for the ongoing devices.
But, I think we have to look at this as a collective and say, people are going to make a lot of money from the devices that win, right? And the winners should subsidize the field, because no one does this alone. I also think, Cal, that all the gaming technology that is related to virtual reality – those things could be taxed at .5%. A very small percent to generate a tremendous amount of money keeping all of these companies viable. At least to sustain people who have devices that are in-dwelling.
But, I think there’s an ethical responsibility to sustain these people. And sadly, the law doesn’t mandate it. And the policies have not sustained it. And now, precisely because of the success of the science, people are now in a position where they have devices that are not being maintained for the long term, and I think it’s a long-term responsibility.
Roberts: This whole area of what some people call electroceuticals, these electric devices that interact with the human nervous system either on the periphery or in the brain, is really becoming a big field. You talked about deep brain stimulators that reduce tremors in people with Parkinson’s disease. But recently, people have sparked interest in using such devices to reverse depression or treat Alzheimer’s or restore mobility. So, this is potentially a big area.
Fins: And cochlear implants as well.
Roberts: Right. So, I know that when I sat on the institutional review board at Cornell, I don’t remember a discussion about the sponsoring company. I don’t remember the discussion about non-abandonment. Tell me what’s happened recently.
Fins: I think these are evolving concerns. There’s a philosopher named Henry Richardson who was Elliot Richardson’s son, who was the Attorney General during the midnight massacre at Watergate break-in. His son is a philosopher, and he wrote a book called Moral Entanglements. He writes about ancillary care obligations. Historically, when we think about research and we think about therapy, investigators, researchers, because they are wont to fall prey to conflicts, did not assume a clinical care role.
For example, if you were doing a scan with a new technology and you discover something, it was a research result. It wasn’t a clinical result. Even if it potentially could help the person that scan. That’s changing now, and we realize that we have an obligation to share those kinds of results if they’re actionable results. And Richardson, writing about the role and responsibility of investigators, talks about ancillary care obligations. That is, these obligations of care that go along with the research activity. That there’s not a bright line distinction between research and therapy, especially when you’re the edge of vanguard work – new knowledge.
So, if you’re putting in a retinal implant and you’re the only ophthalmologist who knows how to do that and deal with the complications and the sclerosis and all the other things or extraction, and the average ophthalmologist can’t do that, all of a sudden you became that person’s doctor as well as that person’s investigator because you have to provide that ancillary care. Even if it’s not part of the research.
I think we have to begin to understand that when we put devices in people, we assume a set of responsibilities. I think we have to broaden the notion that if you’re going to do this research, you need to have the infrastructure to sustain it. The other thing I just want to say, because we have a regulatory system that’s more designed to regulate drugs than devices, that sometimes we analogize the drug situation to the device situation and it’s not a good fit, right?
If you’re doing drug studies you could have a small effect on a million people. And you have a winner. In devices, you need to have a big effect in a small number of people and each one costs a lot more. A pill costs $3 a pill. These devices can cost tens of thousands of dollars. You need to get a big win, and the numbers are different.
The other thing about it, which I think is very important, is that sometimes these devices take years to show their efficacy. And sometimes the companies only pay for a three month window to test efficacy. The situation is, somebody could be in a trial. It fails because, in three months, it didn’t work. They still have the device. It’s still plugging along, and they get better after the trial has concluded that it didn’t work. Why? Because the timeline didn’t fit the biology of the adaptation of the body to the intervention.
Remember, the brain and the eye as part of the nervous system, these are adaptive systems, and it takes time for the brain, the eye, for the cochlear implant to getting engrafted into the nervous system and begin to communicate. And that timeline might be different for a drug to have an effect pharmacologically. So, I think we’re at the stage now with these electroceuticals where we have to have a regulatory system and a financial system that’s respectful of how these interventions interact with biology.
Roberts: Because we have two situations here. We have this implantable device that works, is successful, may go on to commercialization. And then we have the device that was “not successful” – however we define this, does not get commercialized, and the company may be gone. And now, what happens to the patients? What happens to the patients who participated in the trial?
Fins: This is a very hot topic in the research ethics arena right now. We don’t have answers yet, but I think a couple of things. One, I think this is a perfect rationale for insurance. It should be considered part of doing business by the sponsor, by the company, by the universities that are involved, to put aside some money for an insurance premium. If you look at the cost of some of these trials, this is going to be a marginal cost. It’s going to be a few percentage points on the total cost of the intervention. And I don’t think these trials should go forward without provisions for caring for these people and figuring out what to do for these contingencies.
I also think on the front end this all needs to be explained to prospective subjects in a very careful way. You’re in a clinical trial. You really love your doctor He wants you to take this new chemotherapy. He wants to get this implant. Whatever it is. And he’s enthusiastic or she’s enthusiastic because they’ve spent the last 10 years of their life developing this drug or this device. So, they’re going to believe it works, so they’re the one talking to the subject or the patient and they give the sense that it’s going to work. That it’s therapeutic. And they foster what Appelbaum called the “therapeutic misconception.” It’s still research. It’s still investigational. It’s still in what we call “equipoise.” And equipoise is this ethical phrase we use to say we’re in the middle, equally positioned between research and therapy. We don’t know which way it’s going to go, and that’s why we’re doing the trial. We have to demonstrate first safety, and then efficacy. And there are different clinical stages that we go through.
But, one of the problems is when you get consent for these kinds of things, you have to be absolutely sure that people will understand that we’re in research.
Roberts: Does this just apply to research? Or, how about a product that is FDA approved and commercialized, therefore it has demonstrated safety and efficacy, now goes into broader circulation. And doctors who were not part of the clinical trial are using this, implanting this – we’ll take either the case of the retinal implant or the deep brain stimulator – and now, five years later, ten years later, the device breaks down. And there’s no company to back them anymore. The company is gone. Now, what happens to the patient in that case?
Fins: Right. Well, the liability question is very complicated, and I’m not a lawyer. But, devices do malfunction over time. Even established devices when there are established companies. So, there needs to be a cohort of clinicians who can deal with that problem and they can take it out and replace it.
The question is not so much, what do you do when it fails, but how do you replace it? If there is an adequate replacement. Some of these devices also have implications because you can’t get certain tests if you have one of these devices. You can’t get certain MRI studies because they’re magnets, and some of these devices are magnetic. It means you can’t get an MRI scan of your hip if you’ve got hip pain because you have a retinal implant, conceivably.
But, there is a thing called Phase 4 Surveillance. Phase 1 is Toxicity. Phase 2 is Efficacy. Phase 3 is As Good is the Established Care, and then it’s approved through a mechanism at the FDA. And before you start you have to have an investigational device exception called an IDE to even allow this thing to start. So there FDA on the front end and on the back end.
So, the device is approved and you’re in Phase 4. And in Phase 4 there is market surveillance. Because sometimes things happen later on because the numbers in the trial were small, and you didn’t see those effects when you had a study with 25 people which might be enough to get it approved. And then you have done it in 1,000 people and you realize you have to do a recall.
All of these devices need ongoing surveillance because there are always risks. And there’s a mechanism to report those risks.
Roberts: So then should that be part of the FDA approval that the company has to, like your insurance plan, insure the devices so that if the company is no longer there, there is someone, some entity behind them?
Fins: I think it would devolve to the FDA but it needs to be specified in a way that makes it logistically feasible and practical. But you know Cal, this is a huge problem. Again, I want to say we’re victims of our own success. It’s a miracle that these retinal implants restored partial vision to people who probably went through their lives thinking they were never going to see a speck of light again. It’s a wonderful thing. It’s a miracle. And it’s human ingenuity at it’s very best. And the fact that we can’t figure out the bureaucracy to sustain this. The science is harder than the politics and the bureaucracy, but we’re being overmatched by the politics and the bureaucracy.
If we saw this as an ethical challenge, there’s no way we wouldn’t do this. There’s no way we wouldn’t do this. So, I think we need to be moral agents here and speak the need of these people who have lost their vision, who deserve as much sight as possible. Because I think it’s got to be devastating to regain sight and then to lose it again. Some of the stories that I was reading that you shared with me. You’re walking in the subway – you’re able to walk in the subway because you’ve got the confidence to walk in the subway. All of a sudden it goes dark. That’s tragic.
Roberts: Absolutely. You’ve gone through the emotional trauma once and now you’re going through it a second time.
Fins: Right. I can imagine it causes all kinds of reactive depression. My point is, it’s within our capabilities, within our power to fix this.
Another thing I would say is that any device that gets put in now should have the ability to sustain software upgrades. They should be upgradable like your phone. We should be able to upgrade the software without having to replace the device. That should be part of the design characteristic. And, these devices have to work for the individual. When we design things, they have to work with your body habitus. How user-friendly they are.
We need to be sensitive. It’s not just the device. It’s the device in the context of the host, which is a person. And if we have this notion of respect for personhood, which is intrinsic to medical ethical reasoning, then we have to think about the personhood and the dignity of the individual and the device should match the individual. Not the other way around.
Roberts: So much medical advancements require patients who are willing to participate. Even in technology that’s at a very early stage. But, they make a decision that they want to be part of this research. Even understanding that it’s early. What happens when stories such as this retinal implant comes out and patients hear that, while the device that they are considering being part of the clinical study may be great in the long term, the support may be gone. Should that person take a chance on novel technology with this experience of what’s all happened in previous technology?
Fins: For my experience in the neurological space for in-dwelling devices, recruitment is a huge issue. One, you’re putting a device in someone’s brain. It’s invasive. That leads to a lot of people to not wanting reasonably to do that sort of thing. But, the issue of trust and sustainability are things we need to cultivate. Not erode. So, when stories like this come out, it makes recruitment very hard. And you can’t demonstrate the effects and the safety and the efficacy of these devices without subjects.
It’s in everybody’s interest to build up trust, not to corrode trust. At the same time, we have to realize that these people who participate in these trials – they’re more collaborators than participants or subjects. And collaborator means to co-labor. They labor with. And they’re pioneers and they should be rewarded. Not necessarily monetarily, but they should be rewarded with this ongoing responsibility that they’re not going to be, at least, abandoned.
And, if these people participate in early trials, I think there should be all kinds of guarantees for their sacrifice. For the risks that they take. Because we’re not going to advance the science without their help.
The other point I want to make is I’ve written a lot, and in my work at Yale Law School where I also teach, I’ve been writing about the rights of people with brain injury, and the right to these technologies through the prism of American disability law. The Americans with Disabilities Act. The ADA and the UN Convention on the rights of persons with disabilities, whether international law or American law, that the mandate is to maximally integrate people into society. And it’s ultimately a violation of the Americans with Disabilities Act. And there are provisions in the ADA about assistive devices. When it was written in 1990 it was about telephones and TTY and things like that. But, if you narrowly reading it,, you’d say it only adheres to 1990 technology. But it really adheres to this kind of technology. It’s about the idea of integration.
And so, I think there could be arguments that a company that abandons somebody and doesn’t make a provision, has further isolated people, cut them off from society, and violated the integration mandate of American disability law. This is the kind of thing that we’re writing about at Yale.
Roberts: So, the promise of assistive technology is to be able to have people who are visually impaired function better than they’re able to with their limited vision. And, so many of our devices that we use are either handheld or external. But, these ones that are implanted are in a different category because of the fact that you can’t turn them off. You can’t put them in the drawer if they malfunction. They are with you and so really deserve, as you say, a little bit of a different approach.
Fins: They deserve deference, in a way, because the burdens that are imposed by them being there are greater than the external things. The other thing is, they are pathways to develop more knowledge. These technologies breed new technologies. And, the fact that they’re in-dwelling today, there may be an easier way of doing it in ten years that we’re never going to get to unless we develop this generation’s technology. So, not only are we harming people who don’t get it today, we’re also impeding the pipeline of technological development.
The stuff we’re doing today- these retinal implants, these deep brain stimulators, as remarkable as they are relative to 50 or 100 years ago, they’re going to be looked upon primitive and halfway technologies 50 and 100 years from now. We’re only going to get there if we’re able to do this research. So, we’re not only talking about this generation and people with current needs, we’re talking about the future development of innovation. And so, we have to figure both of these pieces out. We have to understand the science and we have to understand the regulatory and financial infrastructure. Most importantly, we have to frame it as an ethical obligation to help. To promote beneficence. As Hippocrates said in Epidemics, “do no harm.” If you put a device into somebody and it gets turned off and it’s in-dwelling forever. It has the potential to get infected or has the potential for preventing you for getting an MRI for other health reasons, it’s causing a kind of harm.
So, we need to figure this out.
Roberts: And, I love your point that we can’t get to the next generation without this generation and we can’t do this generation if we don’t have volunteers who are willing to take part in this generation, knowing that it is this generation and it’s not that generation. And so, we have an obligation to protect people who are giving of their bodies in order to advance science.
Fins: I think this is something that I think people intuitively understand. If you sat down and explained it to them at the review board, if you sat down and listened this far into the podcast you’d understand that. Once you understand these facts, the ethics are pristine. They’re clear. There’s a right thing to do and there’s a wrong thing to do. There’s responsibility and there’s abdication. There’s embracing these moral entanglements and ancillary care obligations, and there’s abandonment at the retinal or neural interface.
This is the kind of case studies we should have in high school in your biology class. In your college biology class. In medical school classes. So that people learn the science in the context of their responsibilities, and they learn some ethics as well. So, when they’re practitioners or when they’re CEOs of companies or when they’re federal bureaucrats, they’ll say it reminds me of that case study I did in high school or in college. There’s a right thing to do and a wrong thing to do. Once you interrogate the facts, there’s nothing to do but take care of these people.
Roberts: As medicine advances, we cannot rely on old frameworks of patient care. We must consider and deliver new ethical, bureaucratic and legal frameworks that correspond with new procedures and the new technologies that make these procedures possible. Like Dr. Fins says, the science is harder. But, frameworks for protecting patients must catch up.
When we consider what innovations technology is making possible today, it’s clear that this conversation is only the beginning.
Did this episode spark ideas for you? Let us know at email@example.com. And if you liked this episode please subscribe, rate and review us on Apple Podcasts or wherever you get your podcasts.
I’m Dr. Cal Roberts. On Tech & Vision is produced by Lighthouse Guild. For more information visit www.lighthouseguild.org. On Tech & Vision with Dr. Cal Roberts is produced at Lighthouse Guild by my colleagues Jaine Schmidt and Annemarie O’Hearn. My thanks to Podfly for their production support.