Vaccines, Regulation, and Patents: A Conversation with Harvard Medical School Professor Dr. Jonathan J. Darrow

Interview by James Jolin

HHPR Senior Editor James Jolin interviewed Jonathan Darrow, S.J.D., LL.M., J.D., M.B.A, an Assistant Professor of Medicine at Harvard Medical School and a Faculty Member of the Center for Bioethics. His research focuses on the intersection of law, innovation, and pharmaceuticals. He received his research doctorate (SJD) in pharmaceutical policy from Harvard University, where he completed an LL.M. program in intellectual property (waived), as well as degrees in genetics (BS), law (JD), and business (MBA) from Cornell University, Duke University, and Boston College. He has served as a senior law clerk at the U.S. Court of Appeals for the Federal Circuit, worked in private law practice at Cooley LLP and Wiley Rein LLP, taught on the faculties of four universities and for the World Intellectual Property Organization, authored several law textbooks, supported the intellectual property divisions of WHO and WTO, and lectured widely on issues of innovation, intellectual property, and FDA regulation. His areas of bioethical interest include patient autonomy as part of pharmaceutical selection and use, disclosure of drug efficacy information in advertisements, physician and regulator conflicts of interest, and trade-offs that occur when insurance coverage is mandated for high-cost but low-value products. The interview below has been minimally edited for concision and clarity.

James Jolin (JJ): You have a very unique and interdisciplinary academic background, focusing on the intersection of law, innovation, pharmaceuticals and bioethics. Could you tell me a little bit about your academic journey and why you decided to enter these fields as opposed to others? 

Dr. Jonathan J. Darrow (JJD): I credit my seventh-grade biology teacher, who first exposed me to genetic engineering. That's a term that was probably more popular in the 1980s than it is today. Five years after that, I decided to study genetics at Cornell. I graduated in three years, and went straight to Duke law school. Then, I took my first full time law job in Silicon Valley. The bulk of what we did at that time was related to the “Dot Com” boom, but I did have the chance to work on a few biotech deals while I was there, including some intellectual property licensing. The real shift, though, happened in 2003, when I switched to a firm in Washington DC, which was then called Wiley, Rein, and Fielding, and they were outside counsel to Mylan pharmaceuticals, a large generic drug company. Based on what I learned during that work, I published my first biopharmaceutical related article in 2007, called “The Patentability of Enantiomers: Implications for the Pharmaceutical Industry.” That was in the Stanford Technology Law Review. 

So at that point, I had been a professor of business law for about three or four years. A couple of years after that, I went back for a fourth graduate degree program, this time a research doctorate at Harvard. I decided to leverage my background and focus on innovation in the drug industry. My original purpose was to suggest changes to the patent law that would promote better innovation in the drug industry, but it pretty quickly became clear that patent law was not really the problem, and that the industry was a lot more complex than the academic articles I had read would suggest. 

For example, it quickly became apparent that the problem was not in the patenting of new drugs, but the mechanisms that the industry uses to get people to buy them: things like de-emphasizing how much—or how little, really—they actually help in many cases, and instead focusing on patient desperation and the seriousness of the disease. There is a lot of smoke and mirrors in the industry, and it is a system-wide problem not limited to the drug companies—the healthcare system as a whole is built on the model of continually doling out medications that, unfortunately, often don't resolve the patient's problem. 

So after that, I completed a post-doc at Harvard Medical School, and I've been a faculty member there since 2016. And that's how I ended up studying innovation in the drug industry, which is what I'm still doing.

JJ: That’s a very impressive background. I'd like to turn to one of the most interesting and relevant issues right now at the intersection of law and medicine, which is the development and regulation of vaccines. I've read your article titled “An Overview Of Vaccine Development, Approval, And Regulation, With Implications For COVID-19.” Could you describe to our readers the regulatory environment surrounding vaccine development and the implications it had on COVID-19 vaccine development? 

JJD: The first COVID-19 vaccine was made available in record time, which surprised me—it was less than a year. And partly that was due to the groundwork having already been laid through research efforts over a number of years prior. But it was also due, I think, to the all-hands-on-deck approach and the tremendous pressure that was placed on the government to act quickly—and the law that was passed in the wake of the attacks of September 11, 2001, which created the emergency use authorization. That's a relatively new procedure. 

The vaccine was made available in record time; it took longer to actually receive approval, which emergency use authorization is not. The success of the COVID-19 vaccines has caused some people to wonder whether we could use a similar approach for other diseases, such as cancer or ALS or Alzheimer's. And I think certainly that we could devote more resources to fund greater research, and speed more treatments to market, in those areas. But it's important to consider some key differences between those diseases and COVID-19—the most important of which is that COVID-19 is an infectious disease. 

There have been attempts to make vaccines for non-communicable diseases such as cancer, arthritis, multiple sclerosis, even smoking and obesity. But in general, those investigational non-communicable disease vaccines have not been particularly successful. And the dramatically effective vaccines that we see are, for the most part, limited to infectious diseases. So in other words, infectious disease is a special category, and we can't necessarily expect to be able to reproduce what happened for the COVID-19 vaccine in non-infectious disease contexts. 

I guess more optimistically, we could also take a lesson from the COVID-19 experience and realize that it does pay—or at least it can pay—to be prepared. Policymakers could consider investing more in basic research, and less in paying for low value drugs. And that's something that I would love to see Congress and other policymakers consider. Of course, it's not easy to predict which basic research is going to be the most important. Right away, it's hard to say what will have the greatest impact in the immediate future. So if we go down that road, we're going to have to accept that basic research is a long term investment, and that it may not pay immediate dividends in every case. 

JJ: With regard to cost and investment, how do we properly incentivize developers to incur the significant financial costs associated with pharmaceutical development, without sort of burdening consumers? Do you think that this is a legitimate trade-off that exists in vaccine development? Or do you think that high pharmaceutical costs are just sort of the result of profit maximization?

JJD: So I do think that it can be helpful to incentivize drug development. There are other ways to approach the issue and which mix of different approaches is an open question that's subject to ongoing debate. 

For example, an alternative to the private drug industry is to have the government directly fund drug development, or the United States could even enter into international treaties to coordinate government funded research at the global level. 

Another aspect of the issue of cost is that, in most cases, we don't actually need to pay high prices. In my view, there's too much attention focused on high drug prices, based on the implicit assumption that costly drugs must have high therapeutic value, and that is simply not the case. About 90% of prescriptions in the US are already dispensed as generics. And of the remaining 10%, many could be replaced with cheaper drugs, or even similar, but not necessarily identical, generic drugs. 

So before we consider price, I think we should consider improving our ability as discerning consumers. Patients, physicians, payers, legislators—we all need to do a better job of being discerning consumers first. And only after you've exhausted that option, start to worry about and focus more on price.

For the very small percentage of drugs that are both highly effective and truly have no less costly alternatives, in those cases, the government could either subsidize the drugs directly or impose some form of price controls, with the recognition that the price controls will reduce incentives to innovate. In the end, innovation does need to get paid for, or it won't happen. But there is no sense paying high prices for drugs that offer little benefit or that could be replaced with less costly alternatives.

JJ: That makes sense. Another dimension of this conversation is whether there is a trade-off between scientific rigor and the speed of vaccine development. In general, how do you think—just from your own research and scholarship—we best balance scientific rigor with the urgent need for pharmaceuticals and vaccines, like those for COVID-19.

JJD: It's not clear to me that pharmaceuticals and vaccines are the only way to control the pandemic. We can look to China, for example, which appeared to have reduced infections to near zero before those types of interventions were available. In the United States, perhaps, we could have used contact tracing more effectively earlier in the pandemic, and maybe it would have been more effective than it was later in the pandemic, when it was tried. We could perhaps have done a better job of insulating the most vulnerable members of our population from exposure to the disease.

Anyway, the non-vaccine drugs that have been made available for COVID-19 are, in most cases, generally not curative. So there's not necessarily as much urgency, as you might think, in getting treatments, and maybe even vaccines, approved, so long as there are other tools that are used effectively. So my view is that, in most cases, and perhaps in the case of COVID-19, it is better and it would have been better to take the time needed to be more rigorous in evaluating some of the treatments that were considered than actually occurred. 

Another way to look at the issue is that we don't need an all-or-nothing system, where drugs are either approved and widely available or not yet approved and available only to clinical trial participants or, in limited circumstances, under expanded access. What I would like to see is a phased introduction of medicines, where the most seriously ill people or those who are at the highest risk of becoming ill, or those most willing to accept risk, are able to and can be exposed to the medicines first; then there would be this gradual expansion to people who are more risk averse, or who have less serious conditions, or for whatever reason want to wait and not be first. 

So the scientific process would occur in parallel with product rollout and with corresponding disclosure to patients along the way. This is completely different from the system that we have now, and I think it would require a dramatic reimagining of the whole system. Right now, we don't really have a system that allows for gradual introduction of a new drug or vaccine. We're tied to this binary issue of approved or unapproved. 

Ultimately, no matter what we do, data should be captured from every patient experience, and the outcomes should be communicated to future patients so that every patient can provide fully informed consent based on the information that's available at the time. Some people call this a “learning healthcare system,” and we are moving toward it, but very slowly.

JJ:  I'd like to turn to another issue that relates to pharmaceutical developments: patent laws. I know that this is obviously a very complex area, and we can't do it justice in the amount of time we have, but could you walk our readers through, broadly, the patent laws in the United States that govern pharmaceuticals? What would you say, broadly, are their goals?

JJD: The patent laws that govern pharmaceuticals are, for the most part, the exact same patent laws that govern every other technology: mining, agriculture, cell phones, business processes, and so on. And the goal is to incentivize invention by allowing the inventor to temporarily exclude competitors. 

There are two big differences, though, that sit adjacent to the patent system in the context of drugs, and the first is the regulatory environment. Overlaid on top of the patent system is the need for FDA approval—this exists only in the case of drugs, not in the case of almost any other product. So what that means is that the patent term is running while drug companies are awaiting regulatory approval. The nominal patent term is 20 years from the date of patent application filing, but the actual exclusivity period, if it's empirically measured from the time of branded drug approval to the time the first generic actually enters the market, is only about 13.6 years. That's unique to the drug industry. 

The second key difference, in addition to the regulatory system, is insurance. Very few patented products are guaranteed to be bought once they're marketed. But insurance does exactly that for drugs, some of which are required to be purchased by law, regardless of their price. The patent system is old; it has been around since 1790—that's the date of the first federal patent Act. 

The insurance industry, on the other hand, did not really expand dramatically in the US until 1965, with passage of Medicare and Medicaid. The expansion of drug coverage in the private sector followed in the 1970s, and there was what you might call a golden period in the 1970s and the 1980s, when some drugs and healthcare in general were reasonably well covered, at least by some employers or those with federal insurance coverage. But drug companies—and healthcare institutions, more generally—quickly learned that if payment was guaranteed no matter how high they raised the price, they were going to keep raising the price. And so now, here we are several decades of double digit growth in prices later, and we're now facing an unsustainable burden of drug and healthcare expenditures. 

So in my view, it's not really the patent system that we need to focus on. In fact, one of the reasons that I think we have not solved the drug price problem is because so many scholars have been focused on the patent system and the problem has been mischaracterized as a patent problem, rather than the much more complex problem that, in my view, it really is. So we need to consider the market and the payment environments that were layered over the pre-existing patent system more than 150 years after that patent system was created. 

A great book, if anyone's interested to learn about the evolution of the US healthcare system is called The Social Transformation of American Medicine: The Rise of a Sovereign Profession and the Making of a Vast Industry by Paul Starr.

JJ: Thank you for the suggestion! You said that there has been undue focus on the patent law system as a means of lowering pharmaceutical costs. And so one question I have then is: do you think that any sort of large changes need to be made to the US patent law system to improve access and accessibility to pharmaceuticals for consumers? Or do you think the goal should just be to look at other issues that impact pharmaceutical costs?

JJD: The changes to the patent system since 1790, for the most part, have been very small. So for example, the original patent term in 1790, was 14 years. That was extended to 17 years in 1861, and it remained at 17 years until 1995, when the starting point of the duration was changed, and the length was changed to 20 years. By contrast, the copyright system has dramatically expanded—that also began as a 14 year duration, but it now can extend more than 100 years, as measured in part by the life of the author. So legislators can adjust the duration, and there have been many other provisions added to the copyright statute. 

The patent statute, by contrast, has changed relatively little. So in terms of whether changes to the patent system need to be made, I would say, in general, no, I don't think there are major changes that have to be made. 

There have been major changes that have been proposed in the past. For example, around 1962 there was a proposal to implement compulsory licensing for drugs. That proposal was never enacted into law, but that would be a major change that could be reconsidered. The risk, of course, is that if compulsory licensing becomes a possibility, it would increase uncertainty for manufacturers. And we might see a reduction in the initial creation of drugs—a long-term cost that might not be entirely offset by the short-term benefit of earlier access to drugs that already exist. 

And so that's the trade off; it's very easy to see the benefits from some of the changes to patent law, because the drugs that you can see, that are approved, that are available, could be made available more quickly and at a lower price. On the other hand, it's very difficult to see the costs of those changes, which are the drugs that don't get developed at all or the drugs that don't get developed until a later date. It's difficult to measure delayed entry of branded drugs, and if they don't get approved at all, you will never have an idea of what those drugs even would have been.

JJ: Thank you for that. The final question I have for you relates to your recent commentary titled “Beyond The High Prices Of Prescription Drugs: A Framework To Assess Costs, Resource Allocation, And Public Funding.” Could you elaborate on the argument that Congress should direct the Government Accountability Office. to study public contributions underlying the highest cost drugs and should require periodic reporting by drug manufacturers and the direct and indirect public funding they receive?

JJD: Co-authored journal articles are always a collaboration and sometimes a compromise, and credit for the ideas that you just mentioned go to my co-author, Donald Light. His view, and the view of many of my other colleagues, is that drug prices should be cheaper in those cases where the government funded much of the research. 

I think that approach is too simplistic. The purpose of the 1980 Bayh–Dole Act was “to promote the utilization of inventions arising from federally supported research.” That's the quotation from the statute itself. The Bayh–Dole Act clarified that private parties that had been federally supported could retain the patent rights to the resulting inventions. So the explicit purpose was to allow private parties to profit from federally funded research, not for the purpose of transferring public funds to private hands, but because Congress was concerned that publicly funded inventions were never getting into private hands, and namely, patient hands in the case of drugs. 

The problem with additional reporting, in my view, is that it will actually increase total development costs; it increases the paperwork burden, for example. Those costs must eventually be passed along to patients or to taxpayers, so I would favor a market solution where patients, doctors, payers, and legislators are more discerning about what they're willing to buy, and how much they're willing to pay, rather than trying to artificially force prices lower, at least in most cases.

JJ: Thank you for your insights on these subjects. Is there anything else you’d like to add? 

JJD: The current pharmaceutical market is internally inconsistent. On the one hand, the United States takes a free market approach to pricing. Drug companies can price drugs however they like. On the other hand, the United States is increasingly taking a socialized approach to paying for drugs. We want to make sure that all drugs are paid for, no matter how expensive they are. Those two philosophies are fundamentally inconsistent with one another. 

Either we need to implement price controls, or we need to embrace a free market approach. The combination of the two, however, is virtually guaranteed to lead to rapidly escalating prices. That is what has happened and is what is going to continue to happen until that ideological conflict is resolved. 

Maybe the most important lesson is that the phenomenon of rapidly increasing prices is not actually limited to drugs. It has occurred for health care costs in general. So I would suggest that we should ask ourselves why health care costs as a whole have increased, and use the lessons learned in the healthcare space as a whole to see if they might also be applicable to drugs. And we should also ask why we're so willing to blame drug companies, but not hospitals, doctors, pharmacies, insurers and other parties in the healthcare ecosystem.