Replies to post #51048 on Biotech Values

[davidal66]

I like that system, Dew. Prove safety in a few primates and dogs and a few paid folks and "let 'er rip." I'd be doing pilot testing left and right with high impact ampakines for ALS, Huntington's before you can say ampa receptor upmodulation. I sent a hypothesis to a leading(actually the top)ALS researcher why a high impact ampa modulator might be of use in ALS through a neuroprotective mechanism and his reply to me(and I'm going from memory from six months ago) was:

"We need a different FDA, lets get the drugs out there fast, really fast. Wait, I sound like Dr. Frankenstein, and, come to think of it, so do you! David, I'm going to rename you Dr. Frankestein for bringing this proposal to me." I called him Igor but I don't think he liked that line.

But, he's still interested in running a high impact through his well-funded lab in Boston. I did it all on my lonesome, sans any help from Cortex. I like the idea of a radical FDA. I have a vision from the movie REDS where Provenge supporters will takeover the FDA palace, burning everything down. See, maybe I am nuts.

[zipjet]

>>My opinion is that what Abigail wants is inconsistent with drug regulation based on clinical trials as we know them. Why would anyone enroll in a clinical trial with a control arm when the desired drug can be had for the asking outside the confines of a trial?

I agree with your statement. And your "why" is well stated.

However, being "inconsistent" will not destroy the clinical trial system, IMHO. Drug trials face that same problem today when the drug at issue is approved for other uses or there are reasonable alternative drugs. (My wife has MS - I am not about to put her in any trial with a control arm.) That did not prevent Tysabri from enrolling and completing the studies. I do not think that allowing drug development companies to expand compassionate use at a profit would end clinical trials as we know them.

DD, if someone you love desperately needed a drug under development and it was in your power to get if for them, would you?

>>This is not crazy, but surely it is radical.

Radical goes both ways. Would you concede that it was "radical" in 1962 to add the requirement that drugs be efficacious?

>>I’ve seen cogent arguments by intelligent posters that the FDA ought not to be in the business of evaluating drug efficacy in the first place ...

I do think that it is beyond argument at this point that our current system is expensive. It is also clear that rational drug policy will never be understood by the common press or public. The press and public displays little or no ability to balance drug risks with disease risk.

Respectfully,

ij

[AlpineBV_Miller]

I’ve seen cogent arguments by intelligent posters that the FDA ought not to be in the business of evaluating drug efficacy in the first place—just have the Agency rule on safety and let physicians and patients figure out the rest.

This is actually the core idea behind the advisory panels. The FDA is responsible for making sure regulations have been followed, data collected, and interpretations of those data are done correctly. The advisory panels should be for making clinical judgments about risk and benefit (note I did not use "safety and efficacy").

Unfortunately, this process is corruptable when division heads get to choose their own advisory panels. If the division head has his/her own "unique" ideas about risk and benefit on a drug, then he/she can construct a panel that rubber-stamps their point of view.

Frankly, I'd trade ACs with moderate conflicts of interest that are centrally chosen over "conflict-free" ACs that are chosen by division heads. I think the process would be much more thoughtful, particularly if an AC panel member rotated to be available throughout the FDA staff discussion and briefing document prep stages as an observer/advisor.

Finally, I think the central problem with the FDA right now is ruling on safety with not enough consideration of the benefit the drugs provide. Politically that's very difficult with clueless groups like Public Citizen running fundraising campaigns based upon the false idea that drugs are "safe" in the first place. Having the FDA focus only on safety likely exacerbates that problem.

[caravon]

The Abigail arguments

"I’ve seen cogent arguments by intelligent posters that the FDA ought not to be in the business of evaluating drug efficacy in the first place—just have the Agency rule on safety and let physicians and patients figure out the rest."

This "intelligent" argument doesn't make any sense for two reasons:
1. There are no perfectly safe drugs. There is always trade-offs between drugs' efficacy [aka benefits] vs safety.
A good example will be the entire antibiotics class of drugs. The most of them do have safety issues. But, the offered benefits handsomely overwhelm their safety problems.

2. Most of physicians are not too good and/or very knowledgeable. Now, everyone of them will be in a business to understand and interpret clinical trials? So, shall we allow one semi-blind to guide another blind?

One possibility would be for medical associations to generate diseases treatment guidelines. Taking into account various conflicts of interests, this approach will not work too well. Just look at numerous cases when physicians harm their patients by inappropriately using approved drugs off-label.

At the end, neither of them (physicians and patients) would like to be in such dreadful situation.