At A Glance
Name: Mark Rothstein
Position: Director of the Institute for Bioethics, Health Policy and Law at the University of Louisville, Ky.
Background: Before joining the University of Louisville, Rothstein was director of the Health Law and Policy Institute at the University of Houston.
Education: JD, Georgetown University
In the newly published book Pharmacogenomics: “Social, Ethical, and Clinical Dimensions” [Wiley-Liss], editor Mark Rothstein and 20 scholars, ethicists, scientists, and business people try to define the boundaries of bioethics, social responsibility, and genetics.
Their task wasn’t easy — pharmacogenomics is a relatively adolescent discipline using embryonic technologies. But the authors’ insights into the vagaries of these technologies, and the strange ethical environment that surrounds it, shed light on the small and not-so-small challenges that will soon face the pharmaceutical industry.
Seat belts and aspirin come to mind: The ride will be a rough one.
“Amid the scholarly debate about research methodology and ethics, regulatory strategies, clinical applications, and economic and legal effects,” Rothstein writes, “there has been relatively little discussion about the views of the public.”
SNPtech Reporter caught up with Rothstein to tap into this discussion.
Why did you write this book?
Because I felt that there was a need for discussion of the ethical, legal, and social implications of pharmacogenomics. It’s a major area of research in academic, biotech, and pharmaceutical settings, and yet there is very little attention being paid to the economics and the legal issues and the ethics and all the other things that are written about in the book.
When and how did you notice that there is an ethical component to pharmacogenomics?
Well, I started getting interested in the topic in the late 1990s — I’d say five years ago — when I was attending various scientific meetings and learning about the new technologies that were being developed for pharmacogenomics. And it occurred to me that no one was thinking about ‘Does the public want this? Would they support research in this area? Would they participate in research in this area? Do they want these kinds of drugs? Will they afford them? Who’s going to pay for them? Who is going to have access to them?’ It seemed to me an appropriate time to start studying the issue in a systematic manner.
Do you think pharmaceutical companies or tool vendors have an obligation to educate the public or themselves about these questions?
I’m not sure that I would say that anyone involved in research or manufacturing has an obligation to educate the public, per se. But I think the researchers as a whole — scientists, pharmacologists, geneticists — I think there is an obligation to at least consider the implications of what they’re doing and make sure we adopt appropriate public policy based on where the policy is taking us.
What are some of the biggest challenges in understanding and incorporating the ethics involved here?
I think some of the problems come from the changed assumptions on which pharmacogenomics is based. In other words, from a marketing standpoint, the whole idea in the pharmaceutical industry was to develop the next blockbuster drug that would have widespread applicability and that would have a tremendous market. Well, pharmacogenomics is based on the premise that we’re going to segment the market into many smaller parts based on the genotype of individuals. And if we do that we can provide more effective, safer treatment.
But then the question is, ‘What is that going to do in terms of the costs for developing the drugs, and the willingness of investors to put up those costs when the returns aren’t there, when the market is too small, or the costs may be so high that many segments of the society will be excluded from access to those drugs?’
Leaving aside the scientific issues, just from a health- care provision perspective, it’s a whole different shift.
Since you came up with the idea for this book, have any of the ethical components within pharmacogenomics improved?
I’m not sure we’ve resolved any of the issues, but I do think that in the last two or three years people have started thinking seriously about the issues. ...
If you were to counsel pharmacogenomics companies or pharmaceutical companies on the use of pharmacogenomics technologies, what would you say?
It’s a very complicated question in that there are so many issues that they might seek advice on — or probably should seek advice from someone on. I think what I would suggest is not to get so caught up in the drug-development stage, in the basic-research stage, that you lose sight of how the product ultimately may be used.
For example, we need to be concerned about increasing off-label uses. If we develop a drug that is for 10 percent of the population, how are we going to reach some level of comfort that the drug is not going to be used by the other 90 percent of the population? And what affirmative steps do you need to take to prevent off-label uses; and if someone is hurt through an off-label use, what are the liability implications? Should we educate the pharmacists and the physicians about the limited usage, and what should the label be like? The questions go on and on.
Do you feel the FDA should play an active role here?
I think the FDA has a major role to play. There is a chapter in the book written by folks at the FDA [David Feigal and Steven Gutman], and I think that the FDA is only now beginning to address these issues, or even [beginning to think] about these issues in any serious way. And so it’s arguable that the FDA is really behind the curve on this. Because the drug companies are going to be presenting it with submission based on genotype-limited trials, and [the FDA] needs to develop policies on when those data are adequate to support an application, and how the usage may or may not be limited by the FDA, and what kind of post-marketing surveillance will the firm need to do. There are many points along the way in which the FDA will need to be involved.
Is the FDA creating a regulatory bottleneck?
I wouldn’t say it’s a bottleneck yet if the FDA does not do anything and isn’t prepared to deal with these applications when they come in. If the FDA doesn’t develop policies that are needed then there certainly will be a bottleneck. But I don’t think there is at this time because we’re pretty much at the research stages now.
But given the recent history of genetics, things happen so quickly that we could be out of the research so quickly that there may well be a bottleneck.
Sounds like they can quickly become inundated.
It could be, given the number of researchers and the number of companies that are working on this.
What are the biggest and most important things you learned from talking to the contributors to the book and reading their entries? What stood out and made an impression on you, and you think will make an impact on the market?
One of the biggest things that surprised me comes from our nationwide public-opinion survey on pharmacogenomics, which [is] included in the first chapter in the book. … I was surprised [in the] many responses to the questions that went against what I’d assumed the responses would be. Let me give you [an example]:
We asked people whether they would be able to afford the new medications. Of course, nobody knows how much they’re going to cost; it’s all speculation at this point. But we were interested in seeing how the speculation might be affected by income levels. We had assumed that if you asked a group of people, ‘Can you afford these new medications?’ that there would be a straight line up, with the lowest percentage of the lowest income levels and the highest percentage of the highest income levels.
And that wasn’t the case. There was a dip in the bracket of individuals who make $20,000 to $25,000 a year, so that the people who said they had the least confidence in their ability to afford these were in the $20,000 to $25,000 range. They were also the people who responded that they were most likely to not have filed a prescription because of its cost. So it got us to thinking, ‘Who are these people?’ And these are the working poor — people who make too much money to qualify for need-based assistance like Medicaid, and yet they’re hourly employees who work for employers who don’t provide any sort of health-insurance benefits and have no assistance. That was a very interesting response.
We also found out that of people making over $100,000 a year, 25 percent of them thought that they couldn’t afford these new drugs.
It became clear to us that there was a tremendous lack of knowledge on the part of individuals about pharmacogenomics. In fact, we tried to measure that in a certain way in the study. We asked, ‘Overall, do you think this kind of research … is a good thing or a bad thing?’ Then we conducted the whole interview for 20 minutes, and taught them [about] pharmacogenomics. The last question we asked them was the exact same question we asked them to begin with.
We wanted to see if 20 minutes of education in the context of asking these questions would affect their response. And there was a fair amount of change, which indicates that their views are not strongly held initially. And the change was more toward a favorable view of genetics.