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 free of charge.
If you enjoy today's podcast,
please subscribe for our website for weekly emails
so that you can continue to enjoy this content.
Let's now begin with Gerald's opening remarks.
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 before that a whole series
of so-called patent drugs that had addictive products
because they were running coding and heroin,
but when that was all banned in 1914,
pharma had to look for a new product.
They did discover insulin in 1922,
but for a while it was an industry without a product,
and then it got the product in World War II
with penicillin, one of the greatest discoveries ever
in human history, and 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, which decimated after the war.
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, and then after years of everybody
saying great things about them,
they sort of pull back and say, oh, maybe not so great.
So that happens over time with Valium and benzodiazepines,
and it happens with methamphetamine.
In the 1960s, the country was dotted with 2,000 diet centers
run by doctors, but after a while,
they were selling amphetamines on the street.
Cerny happens with opioid 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,
and that's the darker side of the tale.
So I love this history of pharma
because it's 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.
First topic is Botox.
It was designed and FDA approved for one purpose,
and then used for another.
Why is that okay?
Botox is a fantastic drug from Alagan
because they marketed originally for people
that were having uncontrollable spasms near their eyes
and also in the throat.
It was approved by the FDA for that 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 than in their practice,
they think is a fair use of that drug.
No testing, nothing else.
Alagan 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.
It 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.
Should patients care that the FDA has not approved
a drug's use for the patient's specified purpose,
if their doctor recommends it?
Botox turned out to be safe for what it was used for,
and so they were right in not caring.
They didn't have to worry about it.
I mean, 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 3,000 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
when somebody says,
maybe we should bring that power in a little bit.
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?
Yeah, one of the most popular drugs being used
for diabetes control,
suddenly some people discovered that my daughter,
I'm taking it to control my sugar,
and I'm using this drug,
and I also seem to be losing some weight
although I'm eating about the same amount.
As that word gets out, people clamor for the drug
because one of the reasons that the pharmaceutical industry
is so successful is people like the idea
that appeal is gonna solve their problems in life.
Why should you have to worry about consuming
1,800 calories a day and cutting down your carbs
and exercising at the gym?
My God, if you can take a drug that's gonna do
that, fantastic, side effects, don't worry about it.
I find it interesting that there was such a short supply
because the rush on it was so big
that people who were complaining about not having access to it
were real diabetics.
Who said, by the way, I can't get my drug anymore
when I go to 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 and 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 has been done on real people
in the real 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?
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 drugs diet used was discussed
on the front page of the Wall Street Journal.
The FDA must be aware of it, it is not a secret.
I went to a birthday party last summer
and the chatter was all about this drug.
The rule is the Botox Rule.
Allegrin knew that thousands of doctors
around the country were prescribing more prescriptions
for their drug for cosmetic purposes
than was being prescribed for spasms.
It was not required by the FDA to say,
by the way, your drugs being used
for something else get an approval.
The marker is this, does the manufacturer in any way
encourage that off-label dispensing?
If they do, they're in trouble.
So if you have a salesperson from a company go out
and say to the doctor, who doesn't know about it?
Oh, by the way, you know 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, you are in trouble.
And if you're 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-OK,
they've done their own internal studies
and they're gonna get approved soon.
You're also in trouble.
So the two act as sort of 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 doctors' 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
may be the wrong word, I hate to use that word.
In your book, you reference 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's nonsense for the industry
to hide behind this fig leaf
and for government regulation to demand misdirection.
What if doctors did not have the unlimited power
to go ahead and do off-label dispensing?
And as a manufacturer, you had to get a modified approval
from the FDA, not a full approval,
but a modified approval for off-label dispensing.
You didn't have to go through three years,
it didn't cost you $100 million.
And 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 like that.
We just don't, unfortunately, but what you said a second ago
about Samantha, for instance, in Sex in the City saying,
I believe in Botox, drug companies love it
if one of their products, very seldom happens,
can become part of the popular culture.
Prozac Nation, written by Elizabeth Wordsell.
Yes, her book was Damming Prozac,
but everybody knew Prozac and knew the idea
that it might be able to lift you out
of a funk and bad depression.
So those moments in which they cross over,
the zeitgeist takes in the drug,
they're celebrating that inside the marketing departments.
In your opening remarks, you mentioned
that at the turn of the previous century,
there wasn't much of a drug industry,
and now we have a vibrant one.
And it reminds me of something my dad said to me
that when he started as a cardiologist in the early 60s,
cardiology couldn't help people with heart disease.
They offered bed rest, they suggested stress reduction,
but they really couldn't help patients.
And today we've got 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 industry,
but you also focus under concerns,
demanding increased regulatory oversight.
Why do you think that the FDA can solve problems?
I hope the FDA can solve problems.
I often think the FDA can't.
Sometimes it causes the problem.
Sometimes the delays and the overregulation.
The public has this perception.
When I say the public, yes, it includes us.
But if I stopped 20 people on the street,
I bet you that 16 or 17 will think
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 is not safe.
It's supposed to blame me in 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 a 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 it more as partners working toward the same goal,
which is public health.
And the problem is the FDA often is adversarial with pharma,
and they are encouraged to be adversarial
by activists and health professionals sometimes
who want to take pharma on.
And that's unfortunate, because the adversarial process
doesn't make them a better regulator.
It actually makes the industry suffer.
During the AIDS crisis,
activists said the FDA was too slow.
Too many people were dying.
We need experimental drugs to be made available,
even if they're going to cause potential relief or consequences.
There's always been a tension
between immediate public health needs on the one hand
and long-term ramifications on the other.
How do you think about that tension?
And what did the AIDS experience teach us?
And can you please contrast that
with the FDA response during COVID?
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,
had 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,
you know, 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 80s, up until the time COVID appears,
first 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 are capable of making a vaccine.
And those companies had a 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 it was impossible
to do.
Farmed did a great job on that.
Journalists assert that they have an important role in society
to inform the public while making a profit.
With pharma, they want to improve public health
and also make money.
With the media, the ultimate consumer buys that product
while the drugs are paid by a third party,
either with an insurance company or the government.
What do you make of the dual purpose mandate
and the indirect payment system for pharma?
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
and you ask the doctor as a patient,
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.
And 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 up 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.
And when the drug works, I'm a big fan of it.
And even when the drug has side effects,
as long as 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 sort of wait because they hope they're gonna go away
and then it doesn't and it becomes a bigger and bigger
scandal and that happens sometimes.
Let's talk about opioids next.
Tell us about the evolving state of pain management.
Up until the mid 1980s, students at medical school
were told that opioids were end-of-life pain treatment drugs
because they were addictive and you had to stay away from them.
And then in the mid-80s, a few doctors said,
we think that opioids have been torn,
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 under-treat pain.
People go to a doctor, they complain about pain.
The doctor says, okay, 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,
okay, 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, by the way,
what's your pain level on a scale of one to 10?
And if you had a pain level that was high,
all the rest of your numbers were good.
That doctor should try to treat it somehow.
And that was the background.
So what I say became the release in 1996 of OxyContin,
the first long-acting release Oxycodone pill,
which was the perfect storm.
You've got doctors thinking of opioid's not as
being as bad as they had before.
Pain needs to be more aggressively treated.
And now this little company out of Connecticut says,
hey, guys, we have a 12-hour acting opioid
that's less subject to being addictive.
What were the implications of the 12-hour OxyContin pill?
Before, if you were in a hospital,
you were getting pain relief through an IV.
That drip could keep you steady.
But if you were taking an instant release pill, Percocet,
it had a three to four hour, five hour,
they said sometimes life, but it really didn't last.
In the first 90 minutes, you got about 60%
of the opioid effect from the pill out.
People who are sensitive to pain say,
okay, 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 slowly,
really didn't last 12 hours,
but they got approval for that.
It lasted more eight to 10 for many people,
but still doubled 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.
But as it was designed, it held the promise
for steady pain relief twice a day,
and that would be a revolution.
Who's to blame if people crushed OxyContin pills
and snorted over the objections of the pharma manufacturer?
Perdue and his 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.
But they still continued through sales reps
to push it for a series of things that the FDA had said,
no to.
So 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 and dozens and dozens
over the years of these key sales meetings with doctors
in which they're still pushing and saying,
by the way, don't tell anyone,
it works for osteoarthritis,
but they're not going to tell you that.
So they too aggressively fan the market.
They didn't just set the fire and then watch it burn,
and say, okay, that's fantastic.
They sort of threw a low gasoline on it as well.
Do you think pain management is a useful practice
that we should treat the pain independent of the disease?
One of the holy grails is effective pain management
without the addiction.
As a high hurdle, there are in fact 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,
we're targeting areas of the country through Appalachia,
looking for people who are experiencing heavy duty work,
pain, and when they moved into those fields,
they were successful.
Now, at a certain point,
the distributors like Amerisource Bergen
and Cardinal Health and others 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.
Nobody was saying,
do you think we have a diversion problem here?
Because they didn't want it sort of ruined it.
Now, the FDA could have been a little bit 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 pain patients.
Next topic is philanthropy and the Sackler family.
Critics of the opioid crisis have condemned
the Sackler family for their misbehavior,
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 arts?
The Sackler brothers do present a great opportunity
to have a debate on that issue,
whether their name should be used
or whether institutions should reject their money,
that they're now promised to them.
Don't want anything for the Madoff family, I get that.
And initially, I think people look at the Sacklers
and say, oh, it's a no-brainer.
OxyContin, they attach themselves to the bankruptcy
of the company, there was almost criminal probes,
they've pled guilty before the company.
These are bad actors, take their names off of 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 psychiatrist 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, nine 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
and was in medical advertising,
but he wasn't involved in the OxyContin.
So the question is, do schools institutions
and 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
and they for years have been trying to get some justice
with a Sackler family or an opioids.
If you ask them, they would say, absolutely not.
Take their name off.
I tend to think now, Arthur was the brainchild
of marketing and now has to pay the price for that
by joining his brothers in losing his status
on those named institutions.
Opioids are addictive.
I'm in pain.
Now what?
The pendulum has already started to swing back
from the first angry response.
What I mean by that is just this a 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,
100,000 people dying a year in the US
between legal prescriptions and illegal things on the street
that they were placing with that.
They really tightened up, they mean medical authorities.
You couldn't prescribe for more than three days
the lowest amount of narcotics that are needed
to alleviate the pain.
You had to go into a database as a doctor
and show that the prescriptions being written,
doctors felt 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
and on the street homeless and everything else.
It's part of their life.
It's a pillar they take.
They had difficulty getting those pills.
Now the government has changed the guidelines to say,
okay, it's the discretion of the doctor.
There's no absolute rule.
I think we'll see a bit more liberalized dosing.
The real question is whether the product can change
and that's the $66,000 question
that I don't have the answer to.
People want to get high and that's 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 you think that opioids are so much worse
than the alternatives?
If anybody thinks it's so much worse than the alternatives
then they've drawn the wrong conclusion
because heroin and fentanyl are worse
than prescription opioids.
All three are bad.
The fentanyl can kill you on 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 of course 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?
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 whatever else or fentanyl or that.
They would do an instant test on it
to make sure that you weren't 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 fentanyl
and a level that will kill you.
They would then substitute it
with what you thought you'd come in with as opposed.
So it became essentially a legal market
and outside they were running a free drug,
free zone in which dealers were offering
in that before they went in
and then you were given a clean needle once it went in.
So is that getting anybody off of their addiction note
became what I call a planned maintenance addiction?
If that's 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.
What are you optimistic about?
Changes in DNA cause cancer, we know that.
And science, pharma companies, biotech companies
are on the edge of possibly revolutionizing
the way that that happens.
There are scientists working on therapies like CRISPR
and BIM and others that think they 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 bodies own natural antibodies
to destroy the tumor without destroying adjacent cells
and organs as chemo, can and radiation can.
This I believe will happen.
I hope in my lifetime it will be revolutionary
and will be much heralded.
That's a breakthrough as big as penicillin
in a different way, not everybody gets cancer
but it's such an overhanging our society
that if that is effective, it's why I'm optimistic.
Thanks to Gerald for joining us today.
If you missed last week's show, check it out.
The topic was diversity, equity
and inclusions bureaucracy under attack.
The first speaker was Jay Green from the Heritage Foundation
who discussed Florida Governor DeSantis's challenge
to the DEI bureaucracy in Florida's public universities.
Jay and I were high school debate partners at Nutria.
Our second speaker was Dr. Stanley Goldfarb
who runs the not-for-profit called Do No Harm.
Stanley is the former associate dean
at the University of Pennsylvania Medical School
where he was responsible for the medical school curriculum
and the author of Take To Aspirin
and Call Me By My Pronouns,
Why Turning Doctors Into Social Justice Warriors
Is Destroying American Medicine.
Stanley will discuss how DEI is harming medical schools,
medical research and medical care.
I would now like to make a plug for next week's program
with Laura Hamilton who is a sociologist
at University of California Merced
and the author of multiple books including Broke
and Who Is Paying For The Party.
Laura is interested in how socioeconomic status influence
who goes to college, how students perform there,
their job prospects and the marriage market.
That discussion should be very provocative.
You can find our previous episodes and transcripts
on our website, what happens next in sixminutes.com.
If you enjoy today's podcast,
please subscribe to our weekly emails
and follow us on Apple Podcast or Spotify.
I would like to thank our audience
for your continued engagement with these important issues.
Goodbye.
.