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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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June 30, 2011

An Unethical Clinical Trial

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Posted by Derek

Well, here's one from the Archives of Internal Medicine that most certainly did get published. It's an analysis of an old clinical trial, STEPS, which was conducted for Neurontin (gabapentin) during the 1990s.

But that's not quite right. The authors find, by analyzing a large trove of documents released during lawsuit discovery proceedings, that STEPS was not really intended to be a clinical trial. Instead, it was a marketing program:

Documents demonstrated that STEPS was a seeding trial posing as a legitimate scientific study. Documents consistently described the trial itself, not trial results, to be a marketing tactic in the company's marketing plans. Documents demonstrated that at least 2 external sources questioned the validity of the study before execution, and that data quality during the study was often compromised. Furthermore, documents described company analyses examining the impact of participating as a STEPS investigator on rates and dosages of gabapentin prescribing, finding a positive association. None of these findings were reported in 2 published articles.

Here's more at Medscape. STEPS was allegedly a Phase IV post-approval trial, but it was unblinded and pretty much uncontrolled. Instead of taking place at a small number of centers, it seems to have been set up to enroll as many physicians as possible (they ended up with 772!), with each of them bringing in a handful of patients.

This is an extremely foul technique, which brings the companies who use it, the entire drug industry, and the whole idea of clinical research into disrepute. For money. I feel like spitting on the floor.

Comments (14) + TrackBacks (0) | Category: Clinical Trials | The Dark Side


COMMENTS

1. passionlessDrone on June 30, 2011 10:35 AM writes...

I took that shit once. Emphasis on once; it was prescribed to me as an alternative to narcotics and I determined that the zombie effect was less desired than the pain and good old self medication. That's a drug that needs a marketing plan alright.

- pD

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2. luysii on June 30, 2011 11:30 AM writes...

Yes, I was asked to participate, and I think they offered money to do so, but it seemed like a lot of work so I didn't do it. I can't claim moral superiority, I was just too busy back then to mess around with all the paperwork. A lot of colleagues used the stuff (which was very expensive back then) and thought that it was helpful. I stuck with dilantin and tegretol. I don't think any of them participated.

As a much older and wiser doc told me when starting out-- the best protection the public has, is a physician so busy that all he/she does is what the OUGHT to do, rather than what they CAN do.

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3. Ellen Clark, Clark Executive Search on June 30, 2011 12:41 PM writes...

Terrible. As you say this adds another black eye to the pharmaceutical industry. Thank you for providing such interesting material that I probably would have missed.

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4. Student on June 30, 2011 12:56 PM writes...

And again, the people that stood to make money from this weren't exactly hurting in the first place..
I know this is getting generic now, but damn those MBAs.

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5. Student on June 30, 2011 12:57 PM writes...

And again, the people that stood to make money from this weren't exactly hurting in the first place..
I know this is getting generic now, but damn those MBAs.

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6. Hasufin on June 30, 2011 1:14 PM writes...

Augh; I'm taking that stuff. And it certainly seems to work for me, but I'm deeply concerned about how it has been marketed and "tested".

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7. Rick on June 30, 2011 3:07 PM writes...

Ah neurontin. Nothing epitomizes the dark side of this industry better than the sad story of neurontin. There's even a chapter in "Our Daily Meds" by former NY Times investigative reporter Melody Peterson titled "Neurontin for Everything!" that catalogued a number of similar trials geared toward expanding the market for neurontin waaaaaay outside it's original indication. If I remember correctly, it reached a peak at roughly 30 different uses (not including floor wax and desert topping), and in about 100% of those cases it didn't do anything. As it turned out, doing nothing proved to be a key advantage for neurontin: it wasn't even toxic!

Permalink to Comment

8. Brad on June 30, 2011 4:52 PM writes...

I think this is the study you are talking about: http://bit.ly/lP15Pq. The article is ungated, whereas I haven't been able to access the Archives of Internal Medicine article. I wanted to see if Epilepsia called the medicine Neurontin or gabapentin. They called it gabapentin.

It's important to separate marketing from the medicine. Gabapentin is excellent for a lot of people. In this study, they took people still having seizures despite taking one or more anti-epileptic drugs. My guess is the majority of patients had side effects from these medicines, BEFORE they entered the study. 44% of people became seizure-free; nearly 50% had side effects when the dose was pushed to high levels. About 10% stopped the medicine because of side effects. It looks like 20-25% of people became seizure-free with no more side effects than what they already had. Seizure-free is a big deal. It means you might be able to drive again. Pfizer/Parke-Davis had a good patient assistance program at the time, so patients who had good results from the drug often could continue it after the study ended.

It looks to me like the study wasn't that bad a study, or, maybe I should say I've seen worse.

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9. cliffintokyo on June 30, 2011 7:17 PM writes...

Some frivolity after all the serious issues that have been addressed this week:

"At least 2 external sources questioned the validity of the study before execution....."

I know that team playing and groupthink are *highly valued* (sic) in our industry, but executing the nay sayers seems a bit extreme, even for big pharma.... ;-)

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10. James on June 30, 2011 10:52 PM writes...

Here is a good example of dollars spent from the R&D accounts that properly should be charged to marketing. And so on with the technical "partnering" with physicians as well. The amount of R&D budget that goes into marketing efforts is not small and is money that makes US-based R&D look more feeble than it is Failing to keep track of the true beneficiaries only contributes to the accountants' zeal in outsourcing technical work.

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11. Morten on July 1, 2011 4:23 PM writes...

It's pretty much just a freaky amino acid. I would expect it to hit everything but most with a low kd.

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12. J on July 2, 2011 7:37 AM writes...

If it's any consolation, I don't think practices like this (while common the 1990's) are very common any more. Pharma does learn its lessons sometimes...

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13. MIMD on July 4, 2011 7:29 AM writes...

Spit on the floor a little more about shenanigans we're likely to see more of moving forward with large, uncontrolled data sets from electronic health records and epidemiological legerdemain:

Forensic Statistics

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14. Still Scared of Dinosaurs on July 5, 2011 6:05 AM writes...

James,

Depends on where you're doing the accounting. Money spent on studies like this are certainly added in when pharma claims $800M to develop a new drug but inside the companies it wouldn't really hit the R&D budget. There's usually a pretty clear distinction between Clinical Research (pre-approval) and Medical Affairs (post) where design and execution are concerned.

Medical Affairs groups do often have responsibility for publications of studies run on the clinical side but they have to answer to the leads on the studies who are very careful not to say anything they can't defend in front of regulators.

I've seen open hostility between CR and MA and a clear sense of superiority on the clinical side. For biostisticians Medical Affairs is where promising careers go to die (for MDs it's Drug Safety).

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