Larry Bernstein
Welcome to What Happens Next. My name is Larry Bernstein. What Happens Next is a podcast which covers economics, finance, politics, and science.
This week’s topic is the Opioid Crisis.
Our speaker today is Gerald Posner who wrote the book Pharma: Greed, Lies and the Poisoning of America. Gerald will speak about the conflict that pharmaceutical firms face with their desire for advancing public health and their profit motive.
We will also discuss the advancement of pain management care, fears of addiction, and the success and failures of OxyContin.
There is much to cover so buckle up.
I make this podcast to learn, and I offer it free of charge. If you enjoy today’s podcast, please subscribe from our website for weekly emails so that you can continue to enjoy this content.
Let’s begin with Gerald’s opening remarks.
Gerald Posner
Topic: Advancing public health
Bio: Author and investigative journalist
Reading: Pharma: Greed, Lies and the Poisoning of America is here
Transcript:
Gerald Posner:
When I first thought about a book about the drug industry, I did not expect to start in the middle of the 19th century. That's when a lot of the companies that we know today, like Charles Pfizer and sons and Charles Squibb and others started their companies.
There wasn't a lot going on in the drug business in the early 1900s. They had had a series of so-called patent drugs that had addictive products because they were running codeine and heroin. But when that was all banned in 1914, pharma had a look for a new product. They did discover insulin in 1922. But for a while, it was an industry without a product. It got the product in World War II with penicillin, one of the greatest discoveries in human history. That revolutionized the industry. What emerges after World War II is the German drug industry, which had been the leaders in the world for producing drugs, were decimated.
The infrastructure was bombed out by the allies in the end of the war and it allowed the American companies who had made penicillin with government assistance to move to the forefront of this new industry into the 1950s, which was the age of antibiotics. That's the story of the modern American drug industry. It takes off from that moment on, and it's this great ride where at times what you find is that the most successful products become so overused because patients become enthusiastic about them. There's a little black market for them, they get abused. Then after years of everybody saying great things about them, they pull back. So that happens over time with Valium and benzodiazepines.
And it happens with methamphetamines and amphetamines. In the 1960s, the country was dotted with 2000 diet centers run by doctors. But after a while they were selling amphetamines on the street. Certainly, happens with opioids later. It happens with SSRIs and antidepressants. This story of the drug industry is great innovation inside the laboratory from scientists who are working on cures and better therapies. And then at the same time, overmarketing from the people in the sales department. What you end up with are big profits, a successful blockbuster drug, but occasionally a trail of patients who are left as victims or with bad side effects. That's the darker side.
I love this history of pharma because it is unlike any other American industry. And in America, it's different than anywhere else in the world because it truly is the only place where capitalism thrives completely. We allow drug companies, for the most part, to set whatever price they want on their product. The market either bears it or not. But that's the way it works in a capitalist system, and I'm a fan of that. Not a fan of high drug prices, a fan of the free market.
Larry Bernstein:
First topic is Botox. It was designed and FDA approved for one purpose and then used for another. Why is that okay?
Gerald Posner:
Botox was marketed originally for people that were having uncontrollable spasms near their eyes and also in the throat. It was approved by the FDA under a law that allowed drugs to get special tax treatment because it was for a very small market.
As doctors were giving it for that condition, they noticed fewer wrinkles. They looked a little smoother in their forehead, around the eyes. As that word spread, Botox became one of the most prescribed drugs in America, but not for an FDA approved purpose. It was for off-label reasons.
The FDA allows doctors to take any drug that's approved by the FDA for one purpose and to use it off-label for any other purpose that they think is a fair use. Allergan was aware of it. They watched the market build for this in literally millions of dollars of sales before they decided to do the testing required by the FDA. Took nearly 20 years before they got the approval for the cosmetic purposes. I guarantee you, Larry, 99% of the people who had Botox injections for cosmetic purposes over those years had no idea that it was not approved by the FDA for that purpose.
Larry Bernstein:
Should patients care that the FDA has not approved a drug’s use for the patient’s specified purpose if their doctor recommends it?
Gerald Posner:
Botox turned out to be safe for what it was used for, so they were right in not caring. They didn't have to worry about it. In 1938 when the government decided to give doctors the right to do off-label dispensing, there were fewer than 150 drugs on the market. Now, we're literally looking at 2,500 to 3000 drugs, some of them highly specialized, and it's not so easy to know that a doctor in another field might be using a drug for a completely off-label purpose. It's a very broad power that we give to physicians. There are no stories about people walking out as the hunchback of Notre Dame and lingering with all types of terrible side effects. But we're only one scandal away from that before somebody says, “maybe we should bring that power in a little bit.”
Larry Bernstein:
Recently, I heard about a pancreatic drug that's being used for appetite suppression that results in weight loss. That's a perfect example of something that was used for one purpose and now being used for another. Can you talk about that?
Gerald Posner:
Here we have one of the most popular drugs being used for diabetes control. People using this drug seem to be losing some weight. People clamor for the drug because one of the reasons that the pharmaceutical industry is so successful is people like the idea that a pill is going to solve their problems in life. Why should you have to worry about consuming only 1800 calories a day and cutting down your carbs and exercising at the gym? If you can take a drug that's going to do fantastic side effects, do not worry about it.
I find it interesting that there was such a short supply because the rush on it was so big that people were complaining about not having access to it; real diabetics who said, “I can't get my drug anymore when I go to a Walgreens or CVS.”
There are no side effects that have been reported yet. But I like clinical trials done by the FDA because you tend to find out if there are side effects for a drug. Sometimes you find out that a drug needs a black box warning because it's so terrible, or it's so bad it doesn't even get approved. But the clinical trial is being done on real people in the world who are paying for the prescriptions. And we will find out in a year or two if there are some long lingering side effects, or in 10 if there's an increased small risk of cancer and then everybody will say, “how could this have been done?”
Larry Bernstein:
The company knows that this pancreatic drug is being used for weight loss for patients who are not diabetics. The physicians know. Who has a duty to take this to the FDA and say, “Hey I'm prescribing this medication for a different purpose.” The drug’s diet use was discussed on the front page of the Wall Street Journal. The FDA must be aware of it. This is not a secret. I went to a birthday party last summer and the chatter was all about using this drug.
Gerald Posner:
It's a great question and really the rule is the Botox rule. Allergan knew that thousands of doctors around the country were prescribing more prescriptions for their drug for cosmetic purposes than was prescribed for spasms. It was not required by the FDA to say, “by the way, your drug's being used for something else.”
The marker is this, does the manufacturer in any way encourage that off-label dispensing? If they do, they're in trouble. If you have a salesperson from a company, say to the doctor who doesn't know about it, “this drug is also being used for weight loss. It's the rage of Hollywood, in New York, and you should be doing it here in Idaho.”
And if you are the doctor, and you are saying to patients, “by the way, it's not approved by the FDA, but the manufacturer tells me it's a-okay, they've done their own internal studies and they're going to get it approved soon,” you're also in trouble. So, the two act as parallel ships, both pretending they don't know what the other's doing. The manufacturer is aware of how the sales are taking off, and where they're being diverted by doctor's prescriptions. They don't stop the doctors from doing that, nor do they go ahead and encourage it. That's where I think the FDA is negligent.
Larry Bernstein:
In your book you referenced Samantha from Sex in the City saying that she doesn't believe in marriage, but she does believe in Botox. Botox is part of the popular culture. I think it is nonsense for the industry to hide behind this fig leaf and for government regulation to demand misdirection.
Gerald Posner:
That's right. And here's the real question. What if doctors did not have the unlimited power to do off-label dispensing? And as a manufacturer, you had to get a modified approval from the FDA for off-label dispensing? You didn't have to go through three years, it didn't cost you a hundred million. Then essentially the public use of that drug for an off-label purpose becomes your test for the FDA's full approval. You could have a moderated program that we just don't, unfortunately.
But what you said a second ago about Samantha in Sex and the City saying, “I believe in Botox,” drug companies love it if one of their products can become part of the popular culture. Prozac Nation, when written by Elizabeth Wurtzel, her book was damning Prozac, but everybody knew Prozac and knew the idea that it might be able to lift you out of a funk and bad depression. Those moments at which they cross over the zeitgeist takes in the drug, they're celebrating that inside the marketing departments.
Larry Bernstein:
You mentioned that at the turn of the previous century, there wasn't a drug industry, and now we have a vibrant drug industry. And it reminds me of something my father said to me, that when he started as a cardiologist in the early sixties. Cardiology couldn't help people with heart disease. They offered bedrest, they suggested stress reduction, but they really couldn't help. And today we have Lipitor and other statins, we also have medical devices that can open arteries. Science and medicine have come a long way. You celebrate the drug industries success in your opening remarks. But you also focus on your concerns demanding increased regulatory oversight. Why do you think that the FDA can solve problems?
Gerald Posner:
Well, I hope the FDA could solve problems. I often think the FDA can't. Sometimes it causes the problem, the delays and the overregulation.. The public has this perception that the FDA is protecting their best interests because they think immediately the FDA is the approval process for whether drugs are safe or not. And they blame drug companies when a drug's not safe as opposed to blaming the FDA.
The public likes the idea of independent government oversight of the pharmaceutical industry to the extent that it can be effective. FINRA is perfect example of how you can have self-regulation, but I think at this stage, it's too late to have the equivalent of that in the drug industry. The question is, can you streamline the process for approvals so that good drugs do not wait in a pipeline forever to get there? They've done that a little bit by allowing expedited fees to be paid. But in addition, can you make the relationship between the FDA and the pharma companies not so adversarial and be more as partners working toward the same goal, which is public health? The problem is the FDA often is adversarial with pharma, and they are encouraged to be adversarial by activists and health professionals who want to take pharma on. That's unfortunate because the adversarial process doesn't make them a better regulator. It makes the industry suffer.
Larry Bernstein:
During the AIDS crisis, activists said that the FDA was too slow. Too many people were dying. We needed the experimental drugs to be made available even if they were going to cause potentially lethal consequences. There's always a tension between immediate public health on the one hand and long-term ramifications on the other. How do you think about that tension? What did the AIDS experience teach us? And can you contrast that with the FDA response during COVID.
Gerald Posner:
AIDS changed the whole timeline sequence in terms of the FDA and getting drugs to market. You had a very slow bureaucracy that just wasn't going to change. Even though you had a new virus that was killing people. It took the activists like Larry Kramer and others at Act Up, that would lay down and say, people are dying, get this drug out and push the FDA.
We didn't have people taking to the streets with signs saying we're dying from Covid. Get the vaccines out as soon as possible. There is little doubt that in the interim of those decades from AIDS in the eighties, up until the time Covid appears in 2020, you had a bureaucracy that was ready to move at a much faster pace. Trump did the right thing. Operation warp speed shoved a lot of money into the companies who could make a vaccine. And those companies had a head start from having worked on a similar vaccine years earlier on a virus that then petered out. So, they were able to do it in record time, and that was the best part of the drug industry. It excelled at doing what many people thought was impossible to do. Pharma did a great job on that.
Larry Bernstein:
Journalists assert that they have an important role in society to inform the public while making a profit. They have a dual purpose. With pharma, they want to improve public health and make money. With media the ultimate consumer buys the product while with drugs its paid by a third party either an insurance company or the government. What do you make of the dual purpose and the indirect payment system.
Gerald Posner:
You hit a key point on this. Drug companies are marketing to patients, but they're also marketing to doctors because doctors write those prescriptions.
Doctors will prescribe a new pill from that's just out. And you ask the doctor, how much is that going to cost me? They have no idea.
Even if they did, it would be useless because everybody pays a different price based upon what insurance they have; those who are on Medicare have a different type of plan. So, the odd thing about pricing here is that as opposed to having a central pricing unit as European countries do. The UK does national health, so they know what the price is because it's being set by a government agency.
To complicate the matters, there's an entire industry that has spread in America that exists nowhere else on the planet called pharmacy benefit managers. They're in between the insurance companies and the pharmaceutical companies and the retail pharmacies getting a rebate from the drug company to promote their drug above other competitor drugs. So, there's plenty of money to be made.
When the drug works, I'm a big fan of it. And even when the drug has side effects, if the company recognizes those in a very short amount of time and acknowledges them and does their best to try to fix them, I don't have any problem with that. My only real problem with pharma is when a hit drug turns out to have side effects and reports are coming into the company, and instead of going to the FDA, they wait because they hope they are going to go away and then it becomes a bigger and bigger scandal.
Larry Bernstein:
Let's talk about opioids next. Tell us about the evolving state of pain management.
Gerald Posner:
Up until the mid-1980s students at medical school were told that opioids were an end of life pain treatment because they were addictive and you had to stay away from them. And then in the mid-eighties, a few doctors said, “that opioids have been tarred and feathered for too long as being overly addictive. They really aren't that bad.” Some of them came to the point that if you gave an opioid for chronic pain, not necessarily end of life, somebody might never get addicted.
That started from Sloan-Kettering, and then it grew. There was no pain management industry or specialty. The idea came into effect that it coincided with a parallel effort to say we undertreat pain. People go to a doctor, they complain about pain, the doctor says, “let's see what's causing it.” Instead, let's treat pain as a standalone item. They pushed that for six or seven years before the Veterans Association said in 1989, “we'll be the first to adopt it.” So, then you went in to see your doctor and you got your blood pressure checked, and you had your heart rate and your pulse taken.
Now they also ask you, “what's your pain level on a scale of 1-10?” If you had a pain level that was high, all the rest of your numbers were good, that doctor should try to treat it. That was the background to the release in 1996 of OxyContin, the first long-acting release Oxycodone pill. You've got doctors thinking of opioids not as being as bad as they had before. Pain needs to be more aggressively treated. Now this little company out of Connecticut says, “we have a 12-hour acting opioid that's less subject to being addictive.”
Larry Bernstein:
What were the implications of the 12-hour OxyContin pill?
Gerald Posner:
Before, if you were in a hospital, you were getting pain relief through an IV, and that drip could keep you steady. But if you were taking an instant release pill, Percocet, it had a three to four hour life, but it really didn't last. In the first 90 minutes, you got about 60% of the opioid effect from the pill.
People who are sensitive to pain say, “give me that pill again.” Maybe they don't wait four hours. So that's subject to the abuse. The idea with OxyContin was that the pill had this invisible polymer layer around it that dissolved. It really didn't last 12 hours, but they got approval for that. It lasted more 8-10 for many people, but still double the amount for anything else. So, you'd get the pain relief but nobody would feel high. Nobody would get such a rush that they would say, “oh my God, I want to do that again.” Of course, you could crush it, you could snort it, but they were hoping that people wouldn't do that. As it was designed, it held the promise for steady pain relief twice a day. And that would be a revolution.
Larry Bernstein:
Who is at fault, if people crush OxyContin pills and snort it over the objections of the pharma manufacturer?
Gerald Posner:
Perdue and its executives learned that the drug was much more addictive and it wasn't working in the higher doses as they had thought. And people were becoming addicted for chronic pain, which they thought wasn't possible. They continued through sales reps to push it for a series of things that the FDA had said no to.
The FDA had seen the test on osteoarthritis and said, “it doesn't work. You can't sell for osteoarthritis.” And yet there are dozens of key sales meetings with doctors in which they're still pushing. So it's a case where they too aggressively fan the market. They didn't just set the fire and then watch it burn. They threw a little gasoline on as well.
Larry Bernstein:
Do you think pain management is a useful practice that we should treat the pain independent of the disease?
Gerald Posner:
One of the holy grails is effective pain management without the addiction. That's a high hurdle. There are research units inside some of the biggest pharma companies looking for alternative treatments for just pain. They just haven't found it yet.
Purdue in particular were targeting areas of the country through Appalachia looking for people who are experiencing heavy-duty work pain. When they moved into those fields, they were successful. Now at a certain point, the distributors knew when 5 million pills were going to a little county in West Virginia that had 2,400 people. And nobody was raising a red flag saying, “do you think we have a diversion problem here?” Because they didn't want it ruined. The FDA could have been more aggressive in taking a look, but the pharma company knew from the start that a big number of pills were saturating a very small area of the country where they couldn't all be used by paying patients.
Larry Bernstein:
Next topic is philanthropy and the Sackler family. Critics of the opioid crisis have condemned the Sackler family for their behavior. But the family has also been a major supporter of the arts contributing works and money to the Smithsonian and the Metropolitan Museum of Art. Recognizing philanthropy gives recognition to the benefactor. What should we do if we later condemn the benefactor for actions unrelated to the art?
Gerald Posner:
The Sackler brothers do present a great opportunity to have a debate on that issue and whether their name should be used, or whether institutions should reject their money. Don't want anything from the Madoff family. I get that. And initially I think people look at the Sackers and say, “wow, it's a no-brainer, OxyContin. They attach themselves to the bankruptcy of the company. They pled guilty before the company. These are bad actors. Take their names off everything, and any institution should say no to them.”
Now, the eldest brother, who was probably the brightest of the three brothers (they were all psychiatrists brothers, by the way, no fools in the Sackler family). Arthur, he's the one with the greatest art collection. He's the one who put together the best private Asian art collection.
He died in 1987, 9 years before OxyContin came out on the market. There's no direct tie to him in OxyContin. I do believe the brothers learned how to promote and market through Arthur. He was the genius who gave them the marketing idea medical advertising, but he wasn't involved in OxyContin. So, the question is, do schools, institutions, Tufts and Harvard, the Serpentine Gallery, and everybody else have to give back the money that came from Arthur and take his name off? His second wife tried to make a strong case that he should be left out. But in the end, the Sackler name was too tarnished.
After the book was published, I dealt with a lot of parents who lost a son or a daughter to opioids. They, for years, have been trying to get some justice with the Sackler family. If you ask them, they will say, take their name off. I tend to think now Arthur was the brainchild of marketing and now must pay the price for that by joining his brothers in losing his status on those named institutions.
Larry Bernstein:
Opioids are addictive. I'm in pain, now what?
Gerald Posner:
The pendulum has already started to swing back from the first angry response. What I mean by that is just this few months ago, there was such a reaction to the disclosures about how opioids were over marketed and overused and how many people had had difficulties. A hundred thousand people dying a year in the US between legal prescriptions and illegal things on the street that they're replacing with, that they really tightened up. Medical authorities couldn't prescribe for more than three days the lowest amount of narcotics that are needed to alleviate the pain.
Doctors thought they were being tracked. So as a result, it became difficult for people who really did suffer from pain and have used opioids for years without becoming street addicts. It's part of their life. It's a pill that they take. They had difficulty getting those pills. Now the government has changed the guidelines, to say it's the discretion of the doctor. There's no absolute rule. So, I think we'll see a bit more liberalized dosing. The real question is whether the product can change. And that's the $64,000 question that I don't have the answer to.
Larry Bernstein:
People want to get high and that is not going away. And they used opioids in a crushed form to do that. Maybe because they were addicted, maybe because they liked it. There are other alternatives like heroin or fentanyl. Why do we think that opioids are so much worse than the alternatives?
Gerald Posner:
If anybody thinks it's so much worse than the alternatives, they've drawn the wrong conclusion because heroin and fentanyl are worse than prescription opioids. All three are bad. The fentanyl can kill you in a smaller dose. Heroin is completely addictive. And a good percentage of those who started off with prescription opioids ended up going to heroin when it became cheaper than filling the opioid prescriptions. Or sometimes went to heroin for their own addiction and sold their opioid prescriptions, which were worth a lot of money per pill.
Now fentanyl is the king of that entire opioid market. About 60% of the death rate is attributed each year to some mixture of fentanyl in the end product.
I like the idea of harm reduction. It's a great name. What do you do to try to reduce the amount of harm to people as they give them an alternative for getting off of drugs? It's fantastic if they have some treatment, but there's a debate over safe injection sites out in my home city of San Francisco. They had one up and running in which you could go in as an addict and you would say, “I have an amount here of street heroin or fentanyl.”
They would do an instant test on it to make sure that you were not getting something that was bad. So, if you thought you had an opioid to inject, they would test it and say, “oh no, this has a fentanyl on a level that will kill you.” They would then substitute it with what you thought you had come in with. So, it became essentially a legal market and outside they were running a free drug free zone in which dealers were offering them that before they went in. Then you were given a clean needle once you went in. Is that getting anybody off of their addiction? No, it became what I call planned maintenance addiction. If that is the business the government wants to get into, more power to them, they can do it, but it's not going to be a very pretty sight.
Larry Bernstein:
What are you optimistic about?
Gerald Posner:
Changes in DNA cause cancer. We know that science, pharma, biotech companies are on the edge of possibly revolutionizing the way that that happens. There are scientists working on therapies like CRISPR that are very close to being able to molecularly edit those genes to prevent cancers from occurring. And in cases in which tumors exist, turn the body's own natural antibodies to destroy the tumor without destroying adjacent cells and organs as chemo and radiation can. I believe it will happen; I hope in my lifetime. It will be evolutionary and will be much heralded. That's a breakthrough as big as penicillin in a different way.
The Opioid Crisis