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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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January 5, 2012

Reaction to Andy Grove's Clinical Trial Proposals

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Posted by Derek

I should mention that Science is publishing some letters that it received in response to Andy Grove's proposal to rework the clinical trial system for drug development.

Sidney Wolfe and Michael Carome of Public Citizen aren't too happy with the idea, as you might expect. Their take, as I would reword it, could be summarized as "Hey, the existing system allows the drug industry to spew unsafe crap all over the market, and this would make it even worse". Actually, the language in their letter isn't far off:

A. Grove proposes returning to the era before the enactment of the 1938 Federal Food, Drug, and Cosmetic Act, when new drugs were marketed in the United States without evidence that they were safe or effective. His irrational and dangerous proposal, which would limit the Food and Drug Administration's (FDA) premarket review of new drugs to phase 1 clinical trials, is premised on the fundamental misunderstanding that such trials can provide proof of a drug's safety and on the misguided belief that it is not necessary to establish proof of efficacy. . .

Grove's proposal would subject patients on a massive scale to haphazard, uncontrolled, poorly regulated experimentation involving drugs with unknown safety and effectiveness. Such a flawed proposal does not deserve serious consideration.

Norman Marcus of the Virginia Cartilage Institute is more even-tempered, and his view is closer to my own blog post:

. . .Grove's proposed system needs some fine-tuning.

Grove correctly leaves the safety issues to the FDA, but he does not address dosage issues, which should also be determined before distribution. He does not explore how virtual clinical research organizations of the future would monitor issues of compliance and establish fair methods of measuring response. Replacing the heralded phase 3 trial with a self-administered trial would indeed save money and introduce the product much sooner to at least part of the potential market, but pharmaceutical companies would need some shielding of liability to protect them from the increased risks inherent in this plan. Because patients and third-party payers would undoubtedly see the new drugs as experimental, the pharmaceutical companies should be required to offer them at nominal cost.

That said, experimenting (carefully) is exactly what we should be doing. . .

Finally, David Borhani and J. Adam Butts (of DE Shaw Research) go right to what I've named the Andy Grove Fallacy:

. . .Compared to the semiconductor industry's gains over the past 50 years, the pharmaceutical industry's productivity must seem disappointing. There exists, however, an important distinction between engineering integrated circuits and discovering drugs. The semiconductor industry's realization of Moore's Law has always benefited from a fundamental understanding of solid-state physics. Conversely, we still don't know how living organisms work; new “components,” as well as interactions between well-known components, are discovered daily. . .This ignorance is the real reason why 90% of drug candidates fail in clinical trials: They simply don't work. The trial process is doing just what we ask of it.

None of these are unexpected reactions, and I'm sure that Grove himself has heard them before (and anticipated these). So where does this leave us? Status quo ante, with everyone having stated their positions?

Comments (12) + TrackBacks (0) | Category: Clinical Trials | Regulatory Affairs


COMMENTS

1. Dylan on January 5, 2012 12:24 PM writes...

I'd really wish you guys would hurry up on all that basic understanding stuff. I'm waiting for the time when next years drugs will have twice the efficacy, half the adverse events and be cheaper to boot.

Permalink to Comment

2. Anonymous on January 5, 2012 12:39 PM writes...

Paul Janssen: "The importance of biotechnological methods should not be exaggerated at the expense of classical methods which will always be far more important."

Sir James Black: "Reductionism in biology merely replaces one type of complexity by a different kind of complexity.
....reductionism does not achieve the aim of simplification."

Permalink to Comment

3. BD Cruz on January 5, 2012 12:43 PM writes...

Would we allow or accept another country to model this sort of laissez-faire drug approval process?

If we wanted a model of safety but no efficacy, what lessons can we learn from the nutriceutical market?

Permalink to Comment

4. David P on January 5, 2012 1:41 PM writes...

If we wanted a model of safety but no efficacy, what lessons can we learn from the nutriceutical market?
That we should just tell people they are good for them and hope the placebo effect does the rest?

Permalink to Comment

5. David P on January 5, 2012 1:47 PM writes...

If we wanted a model of safety but no efficacy, what lessons can we learn from the nutriceutical market?
That we should just tell people they are good for them and hope the placebo effect does the rest?

Permalink to Comment

6. luysii on January 5, 2012 1:57 PM writes...

Ah Sydney Wolfe M. D. Back in the day, he argued that Computerized Axial Tomographic Scans (CAT scans to you) shouldn't be adopted, as they had little added clinical utility Unfortunately I don't have the reference, it's probably back in the 70s -- but this makes him the Paul Ehrlich of medicine. His real impetus, of course, was that they were too expensive. I doubt that his writings on anything else should be listened to. I'm not sure if the turkey has ever practiced.

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7. johnnyboy on January 5, 2012 2:13 PM writes...

I suppose that one could argue (if one was charitably-minded) that Grove's 'ideas' had at least the effect of stimulating some public discussion of the drug approval process, and that this is a positive, as it may have enhanced the neophyte's understanding of the issues. But to me his proposal is so off the wall and so lacking in understanding of the realities involved that any discussions it raised are just wasted time and energy on everyone's part. I really wonder just how much attention Grove would have received if he wasn't a billionnaire. The excerpt of the Public Citizen letter expresses exactly what I think of his proposal.

Permalink to Comment

8. anonie on January 5, 2012 3:30 PM writes...

Not that I agree with Grove, but why continue to give more "advertising" and visibility to his proposals?

Simply another Grove grumping and dumping by Derek.

Permalink to Comment

9. Hibob on January 5, 2012 9:45 PM writes...

"Replacing the heralded phase 3 trial with a self-administered trial would indeed save money and introduce the product much sooner to at least part of the potential market, but pharmaceutical companies would need some shielding of liability to protect them from the increased risks inherent in this plan."

Oh Hell No.
Even If the regulatory framework is adjusted to allow a company to choose to bypass Phase III, companies making that choice should have an even higher exposure to liability, one where assets and insurance would not be protected by bankruptcy filings. Otherwise the "self-administered trial" would just devolve into a PR exercise.

I'd much rather see a system where any loosening of phase III requirements is complemented by stricter phase IV requirements.

Permalink to Comment

10. Dickweed Jones on January 6, 2012 2:38 PM writes...

I am SOOOOO sick of hearing our industry compared to the semiconductor industry. As if one has anything to do with the other. Why not the bowling shoe industry? Makes as much sense.

Permalink to Comment

11. deuxciel on January 6, 2012 3:02 PM writes...

I agree with the second opinion calling for fine-tuning esp. with attention paid to particulars, re:

"self-administered trial would indeed save money"

And, know doubt one would realize a fantastic savings in the number of lives lost on test subjects, given the limited number of knowledgeable investigators in this art.

Permalink to Comment

12. Cybernetic Magician on January 8, 2012 9:57 PM writes...

Re: Grove's proposal would subject patients on a massive scale to haphazard, uncontrolled, poorly regulated experimentation involving drugs with unknown safety and effectiveness.

It figures this would come from an IT person.

Patients are already being subjected to haphazard, uncontrolled, poorly regulated experimentation involving IT with unknown safety and effectiveness - that is, electronic medical records systems and related systems.

See reading list here, for example.

It should be noted that not even the Institute of Medicine can ascertain the magnitude of the risks and the degree of benefit.

Permalink to Comment

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