Telling us what part of the dollar goes where does not explain why office visits are $200 if you pay yourself but the doctor will take $80 ($60 from the insurance co. and $20 co-pay) if you have insurance. It doesn’t explain why you can order a lipid panel over the internet (from Labcorp)for $45 and if your doctor orders it, it will be $65. It doesn’t touch why a LEEP (sp?) procedure is billed at $2000+ but the doctor will take $700 from your insurer.

We need way more transparency in medical costs and billing! Why can’t doctors post their fees? Why can’t hospitals and labs post the costs for their services? Why are hospitals expanding at an almost relentless rate?

50%=Samples
30%=People
20%=Actual Promotional Spend

*DTC comes out of the 20%, probably a third
*Yes, total SG & A > R & D
*R & D 8-10X >DTC

Guess the company:
Net Sales: 74B
Net Income: 9.8B
SG & A: 7.8B

Answer: Phillip Morris

The “file” doesn’t sit unused.

Thanks again, for yours, FDA Reviewer — and JiM — I’ve saved your factiods about the likely “under”-estimation of pharma spending.

Great stuff!

Remember I may have taught you everything you know about what goes on inside FDA, but I haven’t taught you everything I know.

An FDA Reviewer

I believe that some version of this list should be nailed to the door of anyone who makes the usual claims about FDA’s independence with regard to preemption (and a lot of other things).

It’s in my permanent file. Again thanks.

Misdirecting reviewers early as to what is important and what they should be focusing on. (Would you spend a lot of time analyzing if the poor bioavailability when this buccal formulation is swallowed decreases efficacy, when it’s really metabolized to a toxic compound.) Telling reviewers not to analyze the exposures to metabolites in drug interaction studies when it’s the changes in metabolite exposures that results in the toxicity. When data is requested not forwarding the request to the sponsor. Intimidating reviewers by saying the request isn’t needed “it’s nice to know, not need to know” (if I’m going to change a recommendation based on the information then it’s need to know). Reassigning reviewers. Have a different reviewer work on the NDA rather than the one who worked on it all along during the IND. Divying the review up and then have the ‘consult team’ intimidate and harass the reviewer and prevent the reviewer from meeting deadlines or even seeing the raw data.

Set up database systems for the study data that reviewers aren’t familiar with and refusing to provide any useful training so they can actually look at the data.

During presentations of the review findings tie up the entire time by focusing on a minor discrepancy so that the reviewer doesn’t have time left to present safety concerns, and then penalizing the reviewer to trying to refocus the presentation and for what they did/did not present.

Have multiple meetings with the reviewer and 6 managers where the reviewer is relentlessly attacked and then claim that a concensus was reached.

Exclude reviewers from meetings with sponsors about their area or concerns.

For problems that may be related to special populations such as children or the elderly, or with longer duration not have review of these studies part of the original NDA submission and then the day before the deadline ask the reviewer to quickly review the studies (inadequate time to do other than a cursory look at the study and no time to properly analyze the data.

Help companies by directing the trial design e.g. in comparative trials so they can say it isn’t worse than already approved drugs, but the approved drug probably is so bad it should be removed. Tell companies that they can get an indication for combination therapy by studying drug A with drugs B and C when there’s a lethal reaction with Drug D that will certainly be used in combination.

Claim a constellation of AEs that point to a single mechanism aren’t related. Scheduling meetings, etc. when the reviewer is out of the office. Tell reviewers they don’t need to attend certain meetings when it turns out they know there’s something that will be presented that might tip off a reviewer to an issue in their area. Force the reviewer to complete their reviews before they can see information from other review disciplines that by nature the second review discipline builds on, e.g. medical reviews before clinical pharmacology or clinical pharmacology before pharmacology or consults.

Dismiss mechanisms (you can’t call a drug hepatotoxic when the person also has evidence of viral hepatitis, even though all the scientific evidence indicates that this will make the drug induced hepatotoxicity worse).

Telling clinical pharmacologists they have no business looking at formulation, safety, efficacy, or basic pharmacology, and then intimidating other review disciplines not to look at the these issues and preventing disciplines from working together.

I can see how management might work to suppress bad news from the public, but less clear on how that would happen with reviewers. Can you clarify? Does this mean withholding data from reviewers themselves or dividing it up in such a way that the ‘big picture’ is not apparent to any pair of eyes?

While I agree whole heartedly with points 1 - 4 I vigorously disagree with the statement

“the FDA is moving towards only approving products that bring a significant advancement in efficacy or safety”.

This is propaganda that is being promoted by the drug companies. Even if a drug is somewhat less efficatious or somewhat less safe we have to approve them.

In my highly informed opinion some of the drugs that industry has used as examples of this in truth had major safety or efficacy issues that they just happened to get caught on. But then Pharma doesn’t release the nonapprovable letters or the data and even if they did the letter can be written in such a way as to largely avoid the real reason for non-approval. The FD*CA require meetings to be held with FDA after a non-approval to discuss what can be done if the sponsor wants to pursue the drug. Reviewers who raise those safety/efficacy issues can and are excluded.

These actions allow companies legal recourse to get unsafe drugs approved. So if you see a CEO of a drug company complaining about this issue in the press as it pertains with their drug. Then that’s a redflag. It’s kind of hard to go and look at these things retrospectively without knowing the specific examples, but it can be done.

That’s partly true — but it’s also a vast oversimplification. When doing a comparative trial, you have to think about these issues:
1) WHAT competitor’s compound do you study? The best in the current market? The one with the same mechanism of action? The one that is awaiting FDA approval? You can’t do comparative efficacy against all of them — you’ll have to just choose 1. Phase III trials already cost $100 million or more. You are talking about possibly doubling the price of that.
2) What dose do you look at in the competitors compound? Many drugs are given in escalating doses UNTIL they work (think CNS drugs). This would be NIGHTMARE for comparative efficacy studies. What if my drug at 10 mg is better than the competitors at 20 mg. Does that make it a better drug? Maybe, maybe not. It depends on the safety at those doses.
3) What class of patients do you look at? The ones in the original clinical study or the class of patients currently taking the drug? The results could be very, very different. What if my new drug is targeting a different subpopulation? Should I still do comparative efficacy over the standard of care?
4) What do you do with the side effect issue? Many drugs will have comparable efficacy, but a different side-effect profile. What do you do with that information? Is it useful?

In spite of these issues, I do see pharma moving more towards comparative efficacy. Governments and insurance agencies are refusing to buy products unless they are superior to the existing standard of care. And the FDA is moving towards only approving products that bring a significant advancement in efficacy or safety. But so far, no one is doing real “head-to-head” trials to make these judgment calls. (to my knowledge)