COMMENTARY

Pharmaphobia Author: Industry Relations Spur Innovation

Henry R. Black, MD; Thomas P. Stossel, MD

Disclosures

May 28, 2015

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Henry R. Black, MD: Hi. I'm Dr Henry Black. I'm the adjunct professor of medicine at the Langone New York University School of Medicine. I'm here today with my friend and colleague, Dr Tom Stossel. Tom?

Thomas P. Stossel, MD: I am Tom Stossel. I am a hematologist at Boston's Brigham and Women's Hospital and American Cancer Society Professor of Medicine at Harvard Medical School, and at the moment, I'm a visiting scholar at the American Enterprise Institute.

Dr Black: You've been one of the lone promoters of something you call pharmaphobia. In fact, you've written a very good book[1] with that title, if anyone wants to read about it in some detail. I wonder if you could tell us a little bit about why you chose to write this book.

Dr Stossel: I wrote it for two reasons. The first is that I became increasingly aware that there were four facts that many people, including physicians, were not aware of. Fact one is that in the nearly 50 years that I've been in medicine and healthcare, things are much better than when I started out. For example, we live 10 years longer. We're half as likely to die of a heart attack. We hardly ever see people crippled with arthritis. The second fact is the reason for this incredible improvement is the tools that healthcare providers have to use on patients. The third fact is that those tools come predominantly from the drug and medical-device industry. The fourth fact is those tools get to us with great difficulty and great expense. Getting those four facts across was very important.

The second big reason for writing the book is that for the past 30 years, people have denied these facts. They've been saying that if physicians and researchers take payments from the medical-device or drug companies with whom they partner to get these amazing tools, they lose concern about their reputation, they become corrupt, and they perform flawed research or they harm patients. That's just wrong, and the purpose of my book is to set the record straight.

Dr Black: There's a perception too that industry doesn't fund important research. That is not my perception, and I don't believe it's yours either. I think much of what we learn and many of the innovations come not from federal sources or foundations but in fact come from industry. Is that your feeling?

Dr Stossel: I have done research most of my career. Some people say I've had success at it. I'd like to hope that some of the research will eventually help patients. Only through the action of industry will it get there. Physicians and academic researchers don't have the culture, the skill sets, and most important, the resources to get the job done.

Dr Black: Could you tell us a little bit about the Bayh-Dole Act and why that happened? I think this is directly related to the industry/academic partnership that we're all quite used to.

Dr Stossel: Well, actually, partnerships have existed since science and medicine came together. Paul Ehrlich worked with industry to give us the first antibiotics. After World War II, Vannevar Bush wrote a letter to President Roosevelt saying science was "the endless frontier." It helped us win the war, and because of that influence and the space race, there was a big uptake in funding of university research. Fast-forward 20 or 30 years, we were very concerned about our economic competitiveness. The Bayh-Dole Act arose because Congress said, hey, we're funding all this research, and nobody is patenting anything. There's no evidence that there's much university research actually getting into practical use. That's what led to the Bayh-Dole Act, which allowed universities to license technology to industry and reduce the threat that there would be a march through and an appropriation of industry funds because the government had seeded the initial funding.

In truth, Bayh-Dole had less to do with the big upsurge in physician and university industry partnerships than the genetic revolution. The technology that came online that enabled leading scientists to found the genetic-engineering business was more important than Bayh-Dole. There were ways before Bayh-Dole to get technology into industry. Another point is that the culture changed. Before my time it was considered inappropriate for physicians or academics to patent things; that was a bad idea.

Dr Black: Where did this concept of conflict of interest and that anyone who works with industry is dirty come from?

Dr Stossel: Well, some of it comes from the old idea. For the first third of my career when I was doing research I was vaguely aware that medicine was getting better. I was vaguely aware that it had to do with tools that we got, but for all I knew they came from Santa Claus. Then in the late 1980s I was asked to join the scientific advisory board of a biotech company, Biogen. I realized how clueless I had been. I realized that these businesspeople aren't plutocrats in suits. Most important, I realized how difficult and expensive it is to get research from bench to bedside. It had always been sold in the academic institution as a linear, seamless ride, but that just isn't true. Timing is everything. It was just as I was having those insights that, because of a few incidents, people started this attack against industry and against physicians and researchers working with it. It has been going on for 30 years.

I have paid attention to what these people have said, digested it, and I think very few people have done that. If you do that, you realize how there is nothing there. That's what the book is about. If you read it you will see just exactly how most of what is being said is wrong.

Dr Black: You bring up how much it costs to bring a product to market. You quote $2.5 billion. Is that what it costs right now?

Dr Stossel: Well, of course, that's an average. The numbers come from the work of economists, Henry Grabowski at Duke and Joseph DiMasi at Tufts. Over the years, they have taken anonymized data from pharmaceutical companies, which they've used to come up with an average figure. It takes on average 16 years and went from less than $1 billion to over $1 billion and now over $2 billion [to bring a product to market]. The deniers, or what I call the conflict-of-interest narrative instigators, say, oh no, this is not true. Other economists have verified it. Of course, they use the signature conflict-of-interest narrative attack, which is that these people have gotten industry support so you can't trust them. Money motive trumps data.

I have been trying for over 30 years to commercialize something that unexpectedly fell out of my research. It might save lives. I know exactly what it costs. Most important, the high cost doesn't take into account the major factor that goes into the expense of new products, which is the high failure rate. I haven't had anything fail yet, but if I were an established company I would have to cover the nine out of 10 projects that fail.

Dr Black: Right now, industry is spending a lot on compliance with regulations, money that you point out could be much better spent on research and development. How has that happened?

Dr Stossel: Absolutely. When conflict-of-issue issues were raised about 30 years ago, the first response of academic institutions was to establish regulations, nannies who would oversee researchers who were getting industry support. Of course, that slows things down. The assumption was that we needed these nannies because researchers would lie and cheat to promote products to make them rich. That's never happened. In those 30 years there isn't a shred of evidence. It's obvious why that is. No product ever gets into market without being vetted by the FDA. Lying and cheating will almost all the time be picked up by the FDA. Anything that slows things down when it's already difficult and expensive is bad.

About 10 or 15 years ago this regulation moved into other areas of medicine. That's when the pens and meals and all this other industry-sponsored stuff was declared corrupt, and we reached this absurdity that any payment to a physician of $10 or more must be reported to the federal government. The companies have to devote enormous amounts of time and effort to that reporting and would be much better spending that money on research, development, and education.

Dr Black: You bring up the term debarment, something I hadn't heard before. Could you tell us a little bit about that?

Dr Stossel: You're in very good company if you had not heard of debarment, because it's never mentioned. This has to do with those huge settlements that pharmaceutical-device companies have paid to the federal government.

Dr Black: Well doesn't that mean that they are admitting guilt if they do that?

Dr Stossel: No, but bear with me. I need to explain it because it's a little complicated. As our colleagues know, a physician can prescribe only a product that the FDA has approved for some indication, but the physician can prescribe that product for any indication that the physician feels is reasonable. The company, on the other hand, can promote the product only for whatever the FDA approved it for. When the physician prescribes it for an unapproved indication, that's call off-label prescribing. The company cannot engage in off-label promotion.

About a decade ago, a creative prosecutor came up with the idea of using what's called false-claims law that dates back to the Civil War to go after companies for off-label promotion. False claims is when somebody bills the government for a service he or she did not perform, such as Medicare and Medicaid fraud—when doctors bill for services they didn't perform, that falls under false claims. Now with a drug or device, remember it's the physician who writes the prescription. It's the physician who is making the claim. In order for the prosecutor to win an off-label false-claims case, the prosecutor has to prove that the company's devious marketing forced the physician to prescribe off-label (they go after the companies because they have the deep pockets, rather than the physicians).

Now we can talk about what goes into that deviousness claim. It's absurd. Nobody could win a case like that in court. On the other hand, false claims carries with it a penalty called debarment, that basically says that if you lose the case (however improbable), you can no longer do business with the federal government for any of your products. For an established pharmaceutical company that is selling to Medicare and Medicaid, the State Children's Health Insurance Program (SCHIP), the VA system, that's capital punishment. That's why the companies always settle, they don't go to trial. When individuals who get snared in these suits and don't care about debarment go to court to protect their reputations, they win. I have never seen the term debarment in any media coverage of these cases. The articles are riddled with terms like healthcare fraud. No wonder that the public has a low opinion of the industry.

Dr Black: You've talked a little bit about how much time and money is spent on compliance and how such money could be used on research. I have been on an FDA committee. I have tremendous respect for the analysis that they do. I think it's much better than anything I've seen by anybody else. When the FDA approves a product I think you can trust it, and I'm very proud of the FDA for all that they do. What about off-label uses? I'll bring up the Neurontin® (gabapentin) example.[2] As far as I understand that case, there was a physician giving a dinner talk where he mentioned using Neurontin for pain relief, an indication the drug had not been approved for at that time. Now, it seemed to me when that happened that the doctors who were there probably didn't know that you could use it for what was then an off-label use (and for which it was approved within a relatively short time). Do I have that right, or am I missing something here?

Dr Stossel: No, that's pretty much right. It brings up another point. We've focused on research, but when the conflict-of-interest force got into everything in medicine we've seen the banning of many useful activities. It's a long laundry list, but just to mention one is what is called a promotional speaker. That's when doctors talk to other doctors, and that's what you were referring to, use of a product.

Dr Black: Right.

Dr Stossel: Now in the old days, these talks would occur in the evening and often in a nice restaurant. The doctors voted with their feet. They liked it. Then when the conflict-of-interest narrative began to flourish, academic health centers started banning this kind of speaking. Why did they do that? Well, for really snobby reasons. They said that's marketing. That's not education because the companies make the education materials, the PowerPoints, and that's not academic. The reason the companies are making materials is not to insert subliminal marketing messages, it's because of what we talked about a few minutes ago. Whatever is in the scripted part of the talk, whatever the teacher, the educator, the physician says has to conform with what is on the FDA label. That's why they are very nervous about allowing a physician to go off script.

Now before and after the talk a physician is perfectly free to talk about other things, which I think must have occurred in the circumstance you allude to. What's also good about these talks is that in contrast to grand rounds or professional meetings with a huge audience, a doctor can say I have a patient with X, Y, Z, and you're an expert in this area. How would you help me manage this patient? This is good for patient care. We shouldn't be banning it, but it has been banned in many cases.

Dr Black: I'm also concerned that our students and the young in general have been infused with the idea that there is something evil about industry and that you don't want to have detail people (you can explain who they are) come to a hospital and talk to house staff. But I think that's the best time to do that because the house staff is there with their more senior residents and attendings. If there is anything said that isn't right, that's the best time to find that out and to discuss it. What's happening with students and how are they growing up?

Dr Stossel: It was obvious to me as I studied this that what was reported in the most prestigious medical journals was extremely negative and totally emphasized the downside of the industry. I did a study. I looked at over 100 articles in four top-tier journals. It was published in Nature Biotechnology.[3] The results are quite astonishing. Of over 100 articles, 90% emphasized the risk, the downside. Less than half provided any data to support that risk conclusion. Three-quarters made conclusions about bad patient outcomes because of industry involvement. There are no such data. It doesn't exist. Less than 15% even mentioned that there might be another side to the argument, and 3% discussed it. Certainly the emphasis has been on the downside. Now recently we're completing a study of what's taught in medical-school curricula, and it's even worse.

What's interesting is that in my chapter in the book about the demonization of marketing, I make the point that the instigators who write articles and do surveys say that in the old days lots of students had contacts with drug reps and they got goodies from them. They ask: "Did you get good information? Was it useful information?" Overwhelmingly the answer is yes. Were these reps biased about their products? Yes. The conclusion of the article is we need more indoctrination. It didn't even mention the possibility that the students are right. They get it. They get useful information and they are skeptical.

The only saving grace here is that when students get into practice, particularly outside of academic institutions, they are still interacting with company representatives. They'll very quickly learn that for the most part they have useful information to impart. It's hard to know over time. A lot of the young people don't have the perspective that I do about how much better things have gotten and that's because of the tools from industry.

Dr Black: I always thought it was amusing that we train our students to deal with very sick people usually, people whom they almost never see when they leave the training environment. Then they go out into the real world where they have no training about how to interact with these types of patients. I think that's exactly backward.

Dr Stossel: Absolutely.

Dr Black: If there's a question about how to deal with an industry detail person who might be promoting a product, you ought to learn about that when you have residents and attendings with you who can point out the flaws. One way to get more money into research is to put a 5% tax on every prescription. We can't call it a tax. That's a bad word, but if we just got a nickel for every prescription, whether for a generic product or for a branded product and then had a competition for that money, we'd have lots of new money in the system that nobody would really notice. That would be a good way to fund research rather than to make people spend money on lawyers and compliance officers instead of something that might help patients in the long run.

Dr Stossel: I'm at the American Enterprise Institute, so I can't advocate for more taxes.

Dr Black: Even five cents on a prescription?

Dr Stossel: In the late '90s, maybe even earlier than that, the amount of money spent on research by the federal government exceeded industry. Then industry crossed over. Now I think industry spends double what the government does. Industry had traditionally provided fellowship, provided lots of support for professional meetings, which gets demonized by the conflict-of-interest instigators. If our academic leaders were really passionate about medical innovation, they would stop beating up on industry and figure out ways to better access those industry funds. Now that gets to another issue, which I referred to earlier, which is that the academic culture isn't compatible with medical innovation. This isn't my idea, historians and sociologists of science have pretty uniformly said this. Researchers aren't trying to save lives. Researchers for the most part are trying to impress each other. Grant committees are more likely to fund novel findings. They are obsessed with novelty, hypothesis-driven research. I've done that all my life so I'm all for that, but from my experience—and I give examples in the book about how products actually get to patients—it requires fishing, it requires trial and error, taking advantage of serendipitous findings. Those things are not rewarded by federal and other nonprofit granting agencies. We need to rethink all of this federal funding in terms of how it's going to save lives. We need to relook at that to see how we can do that better. Only industry has the resources to really make that happen.

Dr Black: I'm also very amused now when one goes to a meeting and you're asked to say what you knew beforehand, what you knew afterward, and how much you learned from that meeting and whether it's biased. That's supposed to tell you that it was an effective talk. The only way to know if it really helps patients is to do a chart review 6 months later and to see if the physicians actually did what they said they would do and whether the outcomes are any better. Outcomes seem to be missing from a lot of what we do. I want to recommend this book for those of us who think we know the business and for those of us who want to know more about the business. I think it's an excellent way to spend time. Tom, I want to thank you very much for your time.

Dr Stossel: Thank you, Henry. It was my pleasure.

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