Paul Rand: How can you be sure that any of the medications you take are safe and effective?

Jerry Avorn: When a patient gets a medication from their doctor or nurse practitioner, they assume that somebody has looked very carefully at this drug and determined that it is indeed effective for the purposes for which it’s being given to you and that it’s reasonably safe. I frankly think a lot of us doctors believe that that’s all kind of taken care of as well.

Paul Rand: After all, the Food and Drug Administration, which ensures the safety and effectiveness of drugs, is probably one of the most well-known government agencies.

Jerry Avorn: We just assume that the FDA is out there doing its thing and making sure that all the drugs work.

Paul Rand: But, what if that assumption isn’t always right?

Jerry Avorn: Under a lot of pressure from the pharmaceutical industry, over the last decade or so, the FDA has gotten perhaps a little bit too permissive in giving a drug a label of approved, even when all that was really demonstrated was that it made a small change in a lab test that may or may not correlate with improving a patient’s health.

Paul Rand: That’s Jerry Avorn, a professor of medicine at Harvard Medical School, where he built one of the leading research centers for studying medication use, outcomes, and costs. He’s recently put everything he’s learned into his new book, Rethinking Medications: Truth, Power, and the Drugs You Take.

Jerry Avorn: I became concerned about how the FDA’s evaluation of whether a medication works had gotten a little bit looser than one might hope in terms of them giving a pass to drugs that, in the eyes of many of us, had not really been shown to work.

Paul Rand: Avorn’s findings call into question things that most of us assumed we never had to worry about.

Jerry Avorn: How do we know if a drug really works? How do we know that and do we agree with it? How do we know if it’s safe, and why does it cost so much? These are all questions I’ve been working on for decades.

Paul Rand: Of course, it’s impossible to have this conversation without acknowledging that we’re talking about these issues at a time of immense change at many of our public health institutions.

Jerry Avorn: Of course, all of that has taken a somewhat more complicated turn in recent months, where the rethinking is going in directions that I never really expected it to go.

Paul Rand: The studies from Avorn’s center are quite frankly shocking, but he also has straightforward steps we can all take to navigate this complex system.

Jerry Avorn: There’s a number of very straightforward questions that are drawn not just from our research, but from my many years being a prescribing physician of, what would I want my patients to talk with me about?

Paul Rand: From the University of Chicago Podcast Network, welcome to Big Brains, where we explore the groundbreaking research and discoveries that are transforming our world. I’m your host, Paul Rand. Join me as we meet the minds behind the breakthroughs. On today’s episode, our broken drug approval process and how to fix it. Big Brains is supported by U Chicago’s online Master of Liberal Arts program, which empowers working professionals to think deeply, communicate clearly, and act purposely to advance their careers. Choose from optional concentrations and ethics in leadership, literary studies, and tech and society more at mla.uChicago.edu.

How is it possible that the FDA is approving drugs that don’t actually work, and in some cases they might even be dangerous? To get an answer, we need to turn back the clock to the inception of something called accelerated approval.

Jerry Avorn: Well, it started, as many problematic things do, with the very best of intentions. The scene goes back to the late ‘80s, early ‘90s, when the AIDS epidemic was at its height and there was a lot of concern that the approval mechanism that the FDA had put in place in the 1960s, that before 1962 you didn’t have to show that a drug worked. You could just market it. In 1962 in landmark legislation, the FDA was allowed to say, no, you cannot sell this drug until you’ve shown us that it’s effective. But, when the AIDS epidemic hit in the late ‘80s and early ‘90s, there was a concern that that degree of carefulness might have become a little too cumbersome.

The argument was getting made that we needed a better way, given that people were dying at the height of the AIDS epidemic at alarming rates, to say, well, we don’t really know how well this drug works, but it kind of looks promising. Let’s let it out there. That made perfect sense in that time. FDA created this pathway called accelerated approval and it made a lot of sense. It was kind of a social contract with the country. The FDA said we will allow this drug on the market even though its manufacturer hasn’t shown that it really helps patients, but it makes a lab test look better.

If we’re dealing with people with terminal cancer or AIDS, we want to give them a chance to have this drug, especially if it doesn’t seem to be terribly dangerous, and then we’ll ask the manufacturer in exchange for that deal where we’ll let you market the drug before you’ve shown that it works, we’ll let them put the drug on the market and then they will do the follow-up studies to see if the drugs did more than just make a lab test look better or make an imaging study look better, but actually extended the quality of life or length of life or health state of patients. I mean, that’s why we take drugs, we’re prescribed drugs. The difficulty was that that standard then started to get applied to a lot of other conditions where all the drug was make a small change in a lab test, called a surrogate measure, and then the manufacturer never came back and did the mandated follow-up studies it was supposed to do to show that the drug really helped patients.

Paul Rand: You used an example of a diabetes drug to help bring that story to life.

Jerry Avorn: FDA has continued to use its main standard of, does the drug lower your blood sugar compared to nothing, which is its gold standard comparator, and yet what a patient with diabetes wants and what we doctors want for our patients with diabetes is also a drug that will prevent the heart disease, the kidney disease, and so forth. Yet, that is not part of the evaluation process. If you can lower the blood sugar more than, ironically, a sugar pill so-called, then you got yourself a drug and it is left up to the medical community to figure out which ones will actually prevent bad outcomes and which ones will just lower your blood sugar but not necessarily prevent all those bad outcomes as well.

Paul Rand: Well, you mentioned that one of the things that’s supposed to happen on accelerated approval is that there continues to be ongoing testing. But, it sounds like oftentimes that testing is just not occurring as part of what the agreed upon process is.

Jerry Avorn: That is exactly right, Paul, and that is where the system falls apart. There’s nothing wrong with saying we don’t know if this drug really works, it looks promising, this is a fatal disease, let’s put it out there and keep studying it. But, the and keep studying it part is where that social contract falls apart. The FDA kind of requests the companies to do follow-up studies, it even commands them to do so, but in what is sometimes looks from the outside like a pretty cynical ploy, the companies just don’t get around to getting those tests done, and yet they can keep the drug on the market, charge full price for it, and yet it not clearly doing any good for anybody except the shareholders of that company.

Paul Rand: It would be one thing if this loophole were used sparingly for the rarest diseases, but it’s not. In fact, pharmaceutical companies have made extensive use of these expedited pathways far more than most people realize.

Jerry Avorn: There is a talking point that we hear from some folks on the right particularly these days that FDA is sluggish and can’t get out of its own way and that Americans are dying of diseases for which there are drugs out there. None of that is true.

Paul Rand: To put this in perspective, over half of all new drugs in the US now reach the market through some form of expedited review that uses lower standards of evidence. In other words, more than half of these programs originally meant for emergencies have become routine.

Jerry Avorn: That’s really where that particular pathway has gone off the rails.

Paul Rand: There are drugs, as you’ve mentioned, that are shown not to work well, but does that mean there’s a steady stream of drugs being taken off the market?

Jerry Avorn: Unfortunately, that is not the case. Even when those things either fail to replicate or flunk their follow-up studies, they remain on the market because it is very, very hard for the FDA to persuade a company to stop making and selling its drug.

Paul Rand: There is a cold medicine story, if I recall, right, that kind of goes along with this.

Jerry Avorn: Right, phenylephrine is what you’re referring to. I bet that most listeners have it in their medicine cabinet and it’s been there for years. It was the successor to actually a very effective cold remedy that you could get over the counter called pseudoephedrine, or the brand name was Sudafed. That worked great if you had a stuffy nose and you were congested and you wanted to take something to dry yourself out, it worked beautifully. The problem with pseudoephedrine or Sudafed was that it turned out that people who were clever backyard chemists were able to figure out a way to make it into crystal meth.

Paul Rand: Yes.

Jerry Avorn: This became a big cottage industry in some parts of the country. The FDA said we can’t have people going in and buying boxfuls of pseudoephedrine and turning it into meth, so let’s make it hard to get. Yet, the manufacturer said, well, we got a good trade name here in Sudafed and everybody asks for Sudafed, let’s just keep the Sudafed trade name, but let’s replace the pseudoephedrine with another chemical called phenylephrine. Which sounds like a neat idea, except that phenylephrine does not do anything. Study after study has shown that it does not help with congestion.

We’re not talking about life and death diseases here, but when an American goes into a drug store and says, I’ve got this congestion in my nose that’s driving me nuts, and they buy something that is still called Sudafed that used to contain the real active ingredient, now contains a completely useless ingredient, but it’s got the same trade name and they buy it, it’s not doing any good. What troubles me is not that phenylephrine is dangerous, but what troubles me is that they could be taking something that actually is effective, but they’re spending millions and millions of dollars a year collectively on something that doesn’t work. FDA has been unable thus far to get it off the market, even though it has been shown to be ineffective.

Paul Rand: The faulty approval process isn’t limited to trivial drugs. It’s even showing up with life-saving treatments like cancer medications. Consider this. One study found that among new cancer drugs approved via accelerated pathways, only about 1/5th were later proven to help patients live longer, just 20%. The rest were approved based on things like tumor shrinkage or slow tumor growth, so-called surrogate measures, but never confirmed to extend overall survival.

Jerry Avorn: We’ve managed to create a situation where there is such fixation on the surrogate measure that that’s all you need to really show. That unfortunately is true of a lot of medications in many categories, including cancer.

Paul Rand: Well, one of the studies you did was a follow-up study, talked about drugs that were approved on behalf or on the basis of something that is called PFS. Explain to me, if you will, what PFS is.

Jerry Avorn: PFS stands for progression free survival. On the face of it, it’s something that we doctors and most patients feel like that’s a good thing. It’s demonstrating that in a patient with cancer, their imaging studies like their MRI or their CAT scan are not getting worse, or their counts are not getting worse. On the face of it, that seems like a good thing and a drug ought to be approved, at least initially, if it can prolong so-called progression free survival. The problem is that progression free survival sometimes but often not, may not predict actual patient survival. That is, your labs may look good, your imaging studies may look good, but you don’t live any longer than you would have either with no drug or with another drug.

Paul Rand: In 2022, Avorn and his colleagues published a paper in JAMA investigating cancer drugs approved based on these surrogate markers. The results were eye-opening. In nearly every case the drug stated on the market, even if the follow-up trials were never completed. Shockingly, even so if those trials were done and failed to confirm any real benefit for patients. In other words, once a drug was let in the door on a shaky surrogate basis, it largely remained in use, regardless of what subsequent science showed.

Jerry Avorn: I argue, as have many oncologists, that we should not be so enamored of the idea of progression free survival as the final word on whether a cancer drug ought to be approved. We need to say, okay, that gets you in the door. It’s plausible. We should make it available for people who need it. Let’s keep studying it. But in the FDA’s hands, that becomes the final part of the story for too many drugs. The drug’s approved and we never find out whether this progression free survival increase is associated with longer life expectancy, or sometimes as it is, with shorter life expectancy. We sure as hell don’t want that.

Paul Rand: Well, one of the common topics that we find ourselves spending a lot of time on Big Brains is Alzheimer’s.

Jerry Avorn: Right.

Paul Rand: The concept of amyloid plaque has come up with some frequency, and there’s a case of a medication that was designed to treat amyloid plaque that also makes this case.

Jerry Avorn: Right, exactly. The drug was called Aduhelm was the trade name, and the more unpronounceable-

Paul Rand: Have you noticed my tricky way of not mentioning the name so you mentioned it first? It’s working for me so far.

Jerry Avorn: Okay, fine. I’ll even at no extra charge to give you the unpronounceable generic name.

Paul Rand: Thank you.

Jerry Avorn: Which is aducanumab, for you. You’ll notice that all the generic names are much harder to remember and pronounce than the trade names, and this was really a low point for FDA. In fact, my colleague Aaron Kesselheim, who works with me at Harvard and leads a lot of this work, and I had an op-ed in the Times when this debacle occurred, saying that this was the worst decision FDA has ever made. Aduhelm was subjected to a lot of studies by its manufacturer, and you got to give them credit. They spent hundreds of millions of dollars on randomized placebo controlled studies. It’s a drug you have to take every other week intravenously, so it’s arduous for the patient.

Paul Rand: And crazy expensive.

Jerry Avorn: Yes. Yeah, $56,000 was the initial list price of the drug per patient per year. Also, it was demonstrated to cause occasional brain swelling and brain bleeding. Now, all of that might be something one would be willing to consider an okay trade-off if it actually helped with Alzheimer’s. But, the crushing irony here is that Aduhelm did not improve the cognition or even slow the deterioration, importantly, of patients who had Alzheimer’s disease.

In a bit of regulatory jujitsu that appalled many people, the FDA when its advisory committee of outside experts came in and said let’s look at the data, because the company had previously given the drug up for dead. Its statistician said, no, there’s no evidence from all these clinical trials that this drug does any good. But, they had some back channel meetings with FDA in ways that they probably shouldn’t have, and they figured out a way to look at the data in a manner that might suggest that it help people. I quote this famous statement among all of us who look at drug results, which is that if you torture data long enough, you can get it to say whatever you want it to say.

Paul Rand: Yep.

Jerry Avorn: There was a lot of data torturing, but even in the face of that, the outside advisory committee concluded there was no evidence this drug helped patients with Alzheimer’s to either have less memory impairment or even help them deteriorate more slowly, which would’ve been okay if it did that.

Paul Rand: If I recall, not only did it not work, but there was some pretty impactful side effects.

Jerry Avorn: Absolutely, Paul. It can make your brain bleed, and people have had strokes while taking this drug and it can cause swelling in the brain. It ought to be pretty damn good if we’re going to accept that degree of risk and burden.

Paul Rand: Gosh, no kidding.

Jerry Avorn: Not to mention the cost, which somebody calculated that had the drug been used as it was originally priced for all the people that FDA said it was good for, the annual expenditure would’ve been the size of the entire budget for NASA. These were many billions of dollars. Now, I guess if there’s a good side of the story, when there was an uproar that FDA said, okay, well it doesn’t really meet its clinical benchmarks, but retroactively we’re going to approve it because it lowers the amyloid level in your brain, which was never the criterion that it was to be evaluated, but it was one of these surrogate measures. There was an uproar. Dr. Kesselheim and two other members of the advisory committee quit in protest. A lot of healthcare systems, including my own at Harvard Medical School, decided they were not going to give it or pay for it.

Then the coup de grace happened when the Medicare program looked at the data itself. Now until then, the Medicare program always paid for anything FDA approved. They said you guys do the evaluation and approval, we’ll do the paying. But, the approval decision was so egregious and the cost was so astronomical that Medicare said we’re not going to pay for this, because it already had caused an increase prospectively in the premiums that every older person who was in the part B drug benefit program in Medicare would’ve had to pay. It already was having a financial shadow over the whole Medicare system.

Once Medicare said, hey, we’re not going to cover the cost of this drug and all these other healthcare systems and insurers and geriatricians said, we’re not going to use this drug, it ended up dying of its own weight. But, it was not FDA’s finest hour because had we gone with what FDA decided based on this surrogate outcome of it lowers your brain amyloid levels, we would have a drug that was doing no good, causing strokes, being a massive burden economically and clinically, and it would’ve been out there to this day.

Paul Rand: Well, this was a bit of a zombie drug then, because even though it went away after three years, it came back to life as another drug.

Jerry Avorn: Right. It has a cousin that was actually brought to us by the same two companies that brought us Aduhelm that is on the market now and it’s called Leqembi. It has, I guess, the distinction of not having zero clinical effect, but having a trivially small clinical effect, not in making anyone with Alzheimer’s disease better, but in very slightly slowing the rate of decline. Which I don’t want to minimize, but the amount of reduction in the rate of decline is so small that most geriatricians feel it wouldn’t even be noticeable by the patient or the family. Its list price is $26,000 a year, and it also can cause brain bleeding and brain swelling. It also needs infusions where you got to keep coming back for years to get the med that doesn’t work and cost so much. We keep learning the same lesson over and over again, or not learning the same lesson.

Paul Rand: After hearing all of these troubling examples, it’s easy to forget why accelerated approval existed in the first place. Let’s not lose sight of those AIDS patients back in 1992, people facing a terminal illness with no option, pleading for a chance at any possible cure. The original intentions of accelerated approval was altruistic. To give desperate patients hope, even if a drug’s benefits weren’t fully proven yet. Surely we don’t want to throw that away. Is there a way to salvage what the original purpose was while fixing its flaws? Avorn believes there is. His proposed solution is something called conditional approval.

Jerry Avorn: That is such a wonderful thing that the industry doesn’t particularly want to see happen. But, it seems to me a very fair bargain in a kind of social sense would be to say, okay, you’ve got a drug, Mr. Drug Company, that you think works. We don’t see very much evidence that it actually helps patients. It does make some interesting changes in lab tests. Maybe that’ll matter, maybe it won’t matter. Let’s make it available to people to take under supervised circumstances. Let’s evaluate what happens when it’s out there through a variety of careful means. Then within another two or so years, we will know whether it works. People who want it, as long as it’s not going to kill them, can access it. But for God’s sake, let’s not let the company have it available universally and charge full price for it if it hasn’t been shown to work.

That kind of conditional approval would go a long way to getting medications out there, continuing to study them, not having the nation, because ultimately it is all of us who are paying for these drugs that don’t work, whether it’s through our tax dollars through Medicare and Medicaid, or our insurance premiums. One way or another, the companies aren’t paying for these drugs, we are. It would be a way of saying, okay, put it out there. Let’s continue to study it and we’ll make a decision again in two or three years based on that evidence. Then we’ll either take it off the market because it didn’t prove itself or we’ll give it full approval and you can make as much money as you think you ought to.

Paul Rand: But, accelerated approval isn’t the only issue with drug development that Avorn has studied over the course of his career. There’s also the matter of how trials are conducted, how much a drug should cost once it’s been shown to be effective, and the things that we as patients need to know to navigate the system. That is after the break.

If you’re getting a lot out of the important research shared on Big Brains, there’s another University of Chicago Podcast Network show you should check out. It’s called Not Another Politics Podcast. Not Another Politics Podcast provides a fresh perspective on the biggest political stories, not through opinions and anecdotes, but through rigorous scholarship, massive data sets, and a deep knowledge of theory. If you want to understand the political science behind the political headlines, then listen to Not Another Politics Podcast, part of the University of Chicago Podcast Network.

If you’ve been listening closely, you might be wondering about something fundamental. Doesn’t the FDA itself rigorously test these drugs to know what works and what doesn’t?

Jerry Avorn: A lot of doctors, and probably most patients, think that FDA tests drugs. It does not test drugs to see if they work or if they’re safe in humans. What they do is they allow the company that is proposing to sell the drug to design, pay for, and conduct and interpret the results of that study. The FDA does double check and it intervenes periodically and says, you sure you want to do that? But, somebody somehow got enamored of the idea of, look at how much money we can save if the companies will just design and pay for these studies. We don’t have to as a government pay for them. Isn’t that a great deal?

Well, as I try to illustrate, no, it’s not a great deal because often, even though the perfectly conducted randomized trial is one of the best tools we’ve got, very often as we saw in the case of the painkiller Vioxx that was on the market for five years and caused tens of thousands of strokes and heart attacks, if we do leave it up to the manufacturer, understandably, they are going to say, well, let’s design the study in a way that might not reveal some of the risks we’re worried about, or let’s see if we can report the benefits a little bit more robustly than we report the harms. All of that happened with Vioxx.

I guess what I’m saying is, having spent collectively $2.5 billion a year on Vioxx in just the US, those are people’s dollars. Whether it was through the Medicaid program which paid a billion dollars for Vioxx, or individuals going to the drug store or however it came out, we as a public are paying for those drugs. It is a false sense of economy that somehow if we let the company pay for and design and interpret the clinical trial, somehow the public’s going to save money. Rather than saying, no, let’s get a bunch of smart docs, and with patient input together and design the ideal study, and not leave it up to the drug maker, we would actually end up saving billions of dollars over the cost that we think we’re saving by not having to pay for the studies.

Paul Rand: Of course then, we’re also paying for the drugs themselves if they get approved. Even a cursory glance at the US health care industry will quickly reveal that there is something seriously wrong with drug prices in America.

Jerry Avorn: These are not evil people running these companies. They’re running a corporation and they’re responsible to their shareholders. We need to accept the fact that that is the job of a corporation. What we need on the other side is entities, usually in government, but it could be in other places like medical schools, that are there pushing back in the opposite direction on behalf of the public. Saying, okay, you want to depict this drug as God’s gift to everybody and charge a zillion dollars for it. We think it’s actually not so good, and by the way, it’s not worth 1/10th of what you want to charge.

Just like any government or corporation or individual doesn’t just go someplace and buy whatever the price tag says, but they say, gee, this laptop is kind of like this other laptop, but it costs twice as much. Maybe I’ll get this other laptop. The only place we’re not allowed to make those decisions, legally, is for medications where over a series of years, the nation has passed laws that say a drug costs, and this is unique to the US among all wealthy countries, a drug costs pretty much whatever the hell the manufacturer wants to charge for it. That’s not a great way to, we would never do that for anything else the government buys or individuals buy, but pharmaceuticals, because of enormous lobbying, have gotten that written into the regs for what we pay for drugs.

Paul Rand: Well, the argument of course is that the reason the companies say drugs are so expensive is that they have large R&D budgets that’s giving them the resources to create new drugs and get those out to this country and to the world. But, we’re shouldering the burden of that. Is that any truth to that?

Jerry Avorn: There is a grain or maybe a third of a grain of truth to that. It is a great talking point. It has face validity or appeal to it, but we’ve actually looked at that pretty carefully and there’s a couple of facts that get in the way of that very plausible but not totally accurate case. One is that an enormous amount of the expense of developing drugs comes from public dollars paid, at least until now, through the National Institutes of Health, which supports researchers in labs and medical schools and teaching hospitals like mine all over the country to develop, first of all the basic science, which is very risky in the sense that you can’t make money off of it and you can’t immediately charge anyone for it. It’s just the basic building block of everything we need to know to discover new drugs.

But sometimes, as Kesselheim and I and others in our group have shown, there are drugs where it is actually taken right up to the finish line. There’s a notorious example of a drug called Xtandi, which is a great drug for metastatic prostate disease. It was developed 100% at UCLA by some brilliant scientists there, completely on the basis of federal funding. But because of the way the laws are written, they were able to then license it out to a series of companies which basically sold the rights to it from one to the other to the other. It’s now in the hands of both Pfizer and a Japanese company called Astellas, and they market it and they are charging two to six times, to Americans, what people in other countries pay for the very same drug that they are selling to them.

There’s no ambiguity here about how much money did the companies put into that drug. They put a lot into marketing and selling it, but in fact, the development was virtually completely publicly funded, and yet the public does not get a break on the basis of the billions of dollars that Pfizer and Astellas are charging for that drug. Ironically, Americans are paying more for it than people who live in other wealthy countries are paying for the very same drug. There’s ways that that can be dealt with. It’s even written into the law that if a drug is heavily developed by taxpayer funding, the government, if it is not readily available at a plausible cost, can, the phrase is march in and reassert the government’s rights to that patent. But, that has never been implemented by the government. This is a choice that’s been made. The government has never used that right that it has to say, hey, wait a minute. We paid for this drug and now you’re charging exorbitant amounts for it. You can’t do that. We’re going to reclaim the patent. That’s never ever happened, even though it is legally possible.

Paul Rand: When you hear a story like this and then you listen to President Trump talking about that he’s going to come down on the high price of prescription medications and how broken the system is, that must be music to your ears and you’re delighted of all the things they’re doing.

Jerry Avorn: If I believed it, it would be music to my ears, yes.

Paul Rand: Okay.

Jerry Avorn: I find that, I guess we have to thank President Trump for putting back on the agenda of the nation’s consciousness that Americans, as a country, we are paying well over twice as much as the citizens of other wealthy countries. Although, I was interested in a lot of what has come across as anti-pharma rhetoric by the new administration, just the same as they’ve been against the food industry and against a lot of other so-called large monopolistic parts of the country, I have not yet seen anything that would lead to acting on that. On dark days, which are now about 9 out of 10 for me, I worry that that is just kind of a populist argument. We’re going to go after the big drug companies, we’re going to go after big agriculture, we’re going to make America healthy, we’re going to end chronic disease.

I think that those are phrases that voters who aren’t paying a lot of attention will be drawn to. But, I have yet to see anything that is a concrete enactment of any of those values. What I did see, and again, it’s an ironic day to be talking about this, is that within a span of 48 hours, we’ve seen the head of the NIH appear before Congress and advocate for a 20% cut in the NIH budget right after we heard that RFK Jr. fired every single one of the scientists who is responsible for helping the CDC think about the vaccines that we’ve got. I mean, I could not have made up a more dystopian scenario six months ago if I had tried. While it’s interesting to see the rhetoric about we can’t let the drug companies push us around, I don’t think there’s going to be very much activity on that front.

I think the president’s ideas for this so-called most favored nation status, where he will identify a country somewhere in the world and say, what are you paying for Ozempic, guys? Then force the manufacturer of Ozempic to sell it to us at that price, that’s just not doable. It ain’t going to happen. Congress would need to enact that, and Congress already looked at that and said, no, we’re not going to do that. For me, the most compelling evidence that this ain’t going to happen was the day that Trump made what was supposed to sound a very scary statement about getting on top of drug prices, the stocks of the drug industry were trading a little lower before his speech, and once people heard what he had to say, the stocks of the drug industry went way up on the day. They know that this is just talking points and we’re not going to see any reform. Far better would be to do what the Europeans, whom President Trump seems to envy so much around their drug prices, the reason they’re low is that the countries say, we don’t think this drug is worth it. Come back with a price that better matches its value, but we’re not going to do that here.

Paul Rand: There’s a lot of other elements of your book we could talk about, but the part that I want to make sure we get in is this idea of what, as consumers of drugs in this country, we can be doing about it. You have a section that you reference as resources for consumers. Give us some of those ideas that, if you’re asked by friends, well, what should they be doing? This is intellectually compelling, but what does it actually mean to the person who’s listening to this and saying, how do I think about this for drugs in my life or my family’s lives?

Jerry Avorn: That was a very important thing for me to include in the book poll because I wanted, besides all the utterly fascinating discussion of policy and science and so forth, I wanted readers to have something that they could really focus on and say, what should I do about this when I go to the doctor next time? What are some questions? One of the more useful activities that I recommend is what I found very helpful as a doctor, which is what we call a brown bag session where you tell the patient, next time I see you, I want you to bring in everything you’re taking, whether it’s prescribed by me or by some other doctor, or maybe it’s a supplement or maybe it’s an over-the-counter remedy. Dump it in a brown bag and bring it in, and then I would dump it out on the table.

I would often be astonished that, first of all, a lot of patients had not told me, understandably perhaps, about meds they were getting from somebody else, even though I was their primary care doctor. I would say, well, gee, that Motrin that you got from Dr. A is the same as the Advil that you’re taking over the counter, which is same as the ibuprofen that Dr. X prescribed, which is very similar to the Aleve. The patient was taking killer doses of these drugs, and then your doctor could say, gee, I’ve been treating you for this chronic cough for months and months. I didn’t know your cardiologist had you on an ACE inhibitor, which is a common cause of people coughing. If you had told them about the cough, they might’ve known it, but you were talking to them about your blood pressure and me about your cough. It’s one of those let’s all be on the same page kinds of things.

The other important question a patient can ask a doctor is, okay, so what is this supposed to do for me? It’s not being uppity or snotty. A patient has a right to know what every chemical they’re ingesting is supposed to in their body. If this is for my blood pressure, what pressure are you trying to get me to? If this is for some other problem, how will we know if we’re there? Do I take this for the rest of my life or until I feel better? Or in the case of opioids, only if I absolutely have to. We doctors sometimes assume that patients will know how to take the meds we prescribe, but that is a conversation worth having. I recommend that people bring in a pencil and paper with them, because I know when I go to my own doctor, I often glaze over when he’s telling me a bunch of stuff.

Paul Rand: Absolutely.

Jerry Avorn: Write it down. Ask the doctor to repeat him or herself. If they don’t have time for that, try to find another doctor because this is one of the most fundamental relationships that one can have in one’s life. Finally, am I going to be able to afford this? What does it cost? Is there a generic? Is there a biosimilar? Is there something that is virtually as good but will not cost thousands of dollars a year that I maybe can’t afford? That also can be part of the conversation as well.