BY ALAN CASSELS
View original article at Brownstone.org.
This article is in honor of Prescribed Harm Day (also known as Prescribed Harm Awareness Day) observed annually on July 29 to honor individuals harmed or lost due to prescribed psychiatric and medicinal drugs.
“A clear conscience is the sure sign of a bad memory.”
—Mark Twain
What if I told you the Vietnam War never happened?
You’d call me a nutjob, say I was wrong, and woefully ignorant of history.
Someone denying the Vietnam War is impervious to the obvious impact that terrible war had on the lives of millions of people, and the place of America in this world.
What if I told you that Vioxx never happened?
To which you’d likely respond, “What’s Vioxx?”
The questioning started innocently enough. I happened to be mid-banter with a handful of old Navy buddies, guys I’d served with 30 years ago in Canada’s navy. We met at a mini-reunion in a pub. We were talking about our jobs, our kids, and so on. One guy asked me what I did and I decided to answer his question with a question:
“Have you guys ever heard of Vioxx?”
I got blank stares, without exception. Six men and no one had heard about this drug.
These buddies are, without exception, very well read, well-connected and largely successful in their professional lives. Many of us left the Navy decades ago and we’ve become successful businessmen, university professors, entrepreneurs. One of my former Navy buddies is a judge. All of us have at least a Master’s degree and some of us have PhDs. We’re also all the same age–61—having lived pretty full and rich lives.
For me Vioxx was a landmark event. Like the moon landing. Something that has been seared into my memory and formed a big part of how I think about trust in institutions, about drug safety, and about the hegemonic control over health held by big, largely unaccountable companies. Mostly about how drugs can harm and kill for something as innocent as an arthritic knee.
Those blank stares threw me for a loop. How is it everyone has heard of Vietnam but no one, at least not among my educated, middle-aged friends, has heard of Vioxx? Do you know what Vioxx and Vietnam have in common, I asked?
Sixty thousand dead Americans.
That’s where the two events are similar.
Vioxx (rofecoxib) was a blockbuster painkiller from Merck, prescribed to over 20 million Americans alone, withdrawn from the market in 2004 after evidence showed it doubled the risk of heart attacks and strokes. It caused 140,000 excess cardiovascular events in the US, and up to 55,000 excess deaths (often rounded to around 60,000 when factoring related complications).
It was the largest pharmaceutical recall in history at the time, leading to billions in settlements and Congressional hearings.
By contrast, the Vietnam War, for America, lasted about 12 years, and the death toll there, too, was about 60,000 Americans.
As I said in a lecture once: Vioxx is very efficient. It killed 60,000 Americans in a little over four years. It took the Viet Cong three times as long to achieve that.
In a crowded drug market, any manufacturer that wants a piece of the pie needs a niche characteristic of which to take advantage. One of the problems with the established market of what we call NSAIDS—or non-steroidal anti-inflammatory drugs, was that they were notoriously hard on the stomach, often resulting in stomach pain and bleeding.
To capture this niche, Merck’s Vioxx (known as a COX-2 inhibitor) was approved by the FDA in May 1999 for pain relief, particularly in arthritis. To say the drug was approved quickly is not arguable. It enjoyed a quick turnaround from the FDA, a six-month ‘priority review’ due to its perceived therapeutic advantage in reducing gastrointestinal (GI) side effects compared to older NSAIDS like naproxen. Basically, if Merck could prove that its drug was better than the older standby, and safer on the stomach, then Merck was in for a windfall, because the market for relieving pain in arthritis is gargantuan.
The pre-approval clinical trials involved around 5,000 patients across eight to nine studies, focusing primarily on efficacy and GI safety, with short durations (typically 3-6 months) and enrolling mostly low-risk participants.
In any study the devil is in the details. The studies didn’t use standardized procedures for detecting or adjudicating cardiovascular (CV) events, and so not surprisingly, the trials didn’t show an increased CV risk in the initial safety database. The reason for this comes down to basic math: the trials were not powered or designed to rigorously evaluate heart-related outcomes. They didn’t include cardiologists on safety boards and so early internal Merck concerns about potential CV effects were noted but not adequately addressed in trial design. You don’t find what you aren’t looking for.
The FDA can usually be counted on to steer clear of doing the right thing and it was no different with Vioxx. The FDA’s priority pathway expedited review was based on GI benefits, even though the trials were limited in their ability to assess broader risks. Also, Merck’s statisticians pooled data across studies in ways that the FDA questioned but ultimately accepted.
Back in 2000 or so, those of us with an eye on drug safety complained to each other that the FDA officials were succumbing to industry pressure and speeding up Vioxx’s approval without requiring long-term CV safety data upfront. Those of us who complained that the drug simply wasn’t studied long enough nor thoroughly enough were ignored.
But alas, the drug was approved in the US on May 21, 1999, and soon launched, with one of the biggest drug marketing spending sprees in the history of the world. With a TV ad budget exceeding $100 million per year, it became an overnight sensation, a blockbuster that was soon used by over 20 million Americans.
Then the bad news started to arrive.
Post-market concerns emerged quickly but were downplayed. The VIGOR study was launched pre-approval in January 1999, but the results didn’t come out until 2000. That trial confirmed some benefits to the GI tract but revealed a four- to five-fold increase in heart attacks and serious CV events compared to naproxen.
Rather than saying that maybe there was a problem with Vioxx, Merck invented an alternative explanation, saying that naproxen had a “protective” effect on the heart. That was the equivalent of saying “Our drug is not that bad, but the placebo is really, really good.”
Data on Vioxx’s harm was eventually published in the New England Journal of Medicine, but that article was problematic. It omitted three heart attacks from the results and published irregular cutoff dates that made the drug look much safer than it was.
Then came the warnings, demanded by the FDA as it carried out ‘performative regulation.’ They added a label warning in 2002, but took no stronger action.
As they say, greed will eventually get you. This is when the wheels fell off the bus for Merck as they tried to expand the market for Vioxx even further. Wondering if Vioxx could prevent the development of intestinal polyps, the APPROVe polyp prevention study came out in September 2004 and ended the Vioxx dream. It showed a nearly doubling of risk of heart attacks and strokes after 18 months—and Merck voluntarily withdrew Vioxx worldwide.
The delay—over four years from first signals—stemmed from multiple factors: Merck’s control over data analysis and safety monitoring (e.g., conflicts of interest on boards, ghostwriting studies, bamboozling rheumatologists and pressuring critics), aggressive marketing that minimized risks, and the high financial stakes (Vioxx generated billions in sales).
The other main cause for this debacle to unfold as it did was simply regulatory inertia, including inadequate post-market surveillance and reliance on company-reported data. The death toll was unlike anything we’d seen in the modern world.
Seismic Shift in Drug Safety…Or Not….?
It’s understandable why the Vioxx scandal feels like a monumental event to someone immersed in drug safety—like a seismic shift in public health policy, ethics, and corporate accountability.
As my Navy buddy reunion anecdote illustrates, not only has it essentially faded from collective memory outside specialized circles, even well-read, informed, and educated people have never heard of Vioxx. We have collective amnesia over the biggest drug debacle in our lifetime.
How does one explain this?
Unlike the Vietnam War (with its draft, protests, and iconic images like naked children running from napalm strikes) or 9/11 (a jaw-dropping human tragedy unfolding on TV and everyone’s cellphone) Vioxx’s harm was spread out over years, mostly out of sight and out of mind.
Vioxx may have killed a lot of people but mostly quietly and incrementally. Deaths and heart attacks occurred in homes and hospitals, probably mostly among older people, and not in dramatic clusters. The lack of a singular impactful event for the public to visualize or emotionalize means it had little chance of piercing the public consciousness in a searing way.
By 2012, commentators were already noting how the story had “sunk into the vast marsh of semi-forgotten international pharmaceutical scandals,” as newer and more impactful crises took over (such as the 2008 financial meltdown and wars in Iraq and Afghanistan).
For my well-read Navy buddies, who likely consume news on geopolitics, economics, or tech, Vioxx was probably not even a blip on their radar post-2005 because it didn’t intersect with their professional or personal worlds.
Even though in my world, Vioxx hung in the air like a bad odor for years, for others it was clearly not a “water cooler” topic like a terrorist attack. That might have been different were we to see a major Hollywood film like Erin Brockovich to push it into the public’s orbit. As the days go by, Vioxx fades even further into obscurity.
Pharma giants like Merck or Pfizer wield enormous influence over narratives. They employ some of the most sophisticated PR and legal strategists in the world, and through their strategic uses of advertising and marketing budgets can effectively “memory-hole” scandals to protect their brand’s reputation. Merck spent millions on damage control post-Vioxx, including lobbying against stricter FDA reforms and funding “educational” campaigns that shifted blame to “individual patient risks” rather than systemic failures.
It is likely that educated professionals like my friends might skim headlines but miss depth on health policy unless it affects them directly; pharma scandals often get lumped into “corporate greed” tropes and have little sticking power as unique events.
In drug policy circles, Vioxx remains a touchstone because it exposed flaws in post-market surveillance and industry-FDA coziness, but for the general public, it’s just one blip in a sea of forgotten outrages.
Today, July 29th is Prescribed Harm Day. We would all do well to simply remember the Vioxx saga and how it can serve as a modern parable of greed, oversight failures, and human cost.
There are many more hidden Vioxxes in our medicine cabinets, which exist due to systemic flaws in drug regulation that allow dangerous medications to flood the market, harm millions, and linger far too long before reluctant regulators pull the plug.
Being slightly older, I have been haunted by another FDA screw up my entire adult life. Approved for pregnant women in 1947, DES was prescribed by caring physicians to help prevent miscarriages into the 1950s. Thankfully, if was given in sequentially higher does & at 7 months I was born & did not develop cervical cancer. The use stopped by 1979 after studies showed multiple problems across generations. The FDA withdrew it for human use in 2000. At least it wasn't Thalidimide. The FDA/Pharma scam has a long history. It has gotten hard to trust anything but herbs, and some of them are suspect as marketed.