Trashing the FDA

[Guest guest]

If I'm not mistaken, Karl has been 'inside' with the FDA as part of their

process. I believe he has been a patient representative or similar with the

group. He obviously has a different viewpoint than the rest of us, since he

identifies with the organization.

We all seek that happy place were exciting drugs that hold a lot of promise get

to sick patients immediately. I remember a story about a man in the hospital,

very sick with CML, no options for him, getting ready to die, who was given

Gleevic as part of a clinical trial. A week later, he was on the golf course.

No word on the hundreds of other CML patients in a similar situation who

desperately tried to get on the trial, who were denied. They are silent, in

their graves.

I assume their families are still bitter this life-saving drug was not available

to their loved one. To be so close...

But. There are few Gleevics around. CML is caused by one specific genetic

abnormality that could be affected by Gleevic. Few other cancers are that way.

And even Gleevic has some toxicity.

It's all about compassion and helping those desperate patients. When you are at

the end of your rope, you will grasp at anything that looks even vaguely similar

to a rope. That's why Mexican quack clinics and various weird ozone machines

and the like continue to sell. Desperation.

I think the Abigail Alliance and similar groups are looking for an expansion of

the compassionate use program. By protecting companies, and putting the risk

for taking the drug on the patient, and not the company, and for providing for a

means to pay for the manufacture of the drug, there is the hope that the very

sickest patients don't die waiting.

I don't think very many people could argue that the compassionate use program

couldn't be expanded.

I'm not trashing the FDA. But it's a bureaucracy. Government employees learn

quickly that the first and foremost rule is...Cover Your Rear-end. You don't

get hammered down if you do nothing. You might if you do something that ends

with lots of bad publicity for the agency. Ergo, slow and slower is the best

way to go, for the employee and the agency.

Re: FDA

Posted by: " karlamonyc "

karls@...

 

karlamonyc

Mon Jan 10, 2011 1:09 pm (PST)

I see. Thank you. In that case, I believe the sponsor should focus on

convening independent experts and patient representatives to discuss with FDA

what trial design (endpoints, eligibility, response criteria, etc) are needed to

demonstrate this kind of response and possible benefit to patients.

Showing that a drug can delay (with minimal toxicity) time to progression, for

example, could well be persuasive in a population not in need of treatment.

I expect that such a study could ethically randomize to the agent versus

observation in this setting, because no treatment is needed. A crossover could

be allowed - for those who progress in the observation group.

Could FDA approve for marketing based on such data? I truly expect so, but the

decision (you don't know how persuasive until you test) would depend on the

toxicities and the magnitude of the benefit - does it delay PFS for a few months

or years ... with consideration of possible offsetting toxicities and hits on

quality of life ... as you know (but for the benefit of those following the

discussion).

Anyhow, my concern is that a valid issue about trial design has somehow morphed

into let's trash the FDA and do away with standards for evaluating new drugs.

No? I feel strongly about this issue because I've spent the better part of the

last 12 years following and sometimes participating in the review process and

from that experence I have now much respect for the process, (which I didn't

have going in - based on abundant misinformation about FDA on the internet.)

For anyone deeply suspicious of the process I recommend that you read carefully

the transcipts of any advisory committee review of a cancer drug ... you may

disagree with a committee's decision, but I expect you will see that the process

has integrity, that the issues are complex, and that patient protection is the

primary concern.

Karl

[Guest guest]

Thanks, . Just to clarify, the FDA patient representative/consulting

programs does not give participants ANY insider influence with FDA policy or

decisions - which is based on Congressional legislation.

We receive training, monthly, and are sometimes invited to participate in review

activities: advisory committe meetings, end of phase II meetings with sponsors,

and so on. FDA doesn't communicate it's expectations regarding our role, accept

to remind about the law and that we are present in order to represent the

patient perspective.

To be included in the program you also need to be a caregiver or survivor - a

person with direct or near-direct experence with the disease and the treatments.

I would not characterize my viewpoint as one that identifies with the FDA, but

as one that understands and appreciates the drug approval rules and the

rationale for those rules (from many years of study and some direct experences)

- which is to make sure a drug helps and does not harm patients.

Again, I have no insider status at FDA. I am called upon sometimes to

participate ... so far in 4 advisory committee deliberations, 3 for cancer

drugs, one for a drug to treat DVT in cancer patients. I've presented on the

role of patient reps in advisory committees at an FDA workshop, and as faculty

in the Accelerating Anticancer Agent Development and Validation Workshop (for

the industry) and have provided input on one approved biologic label. I have

also submitted commentary on the expanded access program (after having read the

proposed changes of course) and have submitted unsoliticited comments on other

issues as I see fit.

My identification, first and foremost, is to patients; and I believe the

standards for the approval of new drugs clearly serves the best interest of

patients, present and future In my view, the approval of all new drugs based

on phase I safety data (they all have toxicities btw) would do signficant harm

to patients and to the ability to make progress against the disease.

The expanded access program is difficult to use, but not because of FDA. (And we

have used it, personally, twice) The primary obstacles being the sponsor (who

must agree to provide the drug and can't be forced to) and the physicians (who

are busy with case load and may not agree with the wisdom of single agent use of

an insufficiently tested drug).

see http://www.lymphomation.org/expanded-access.htm for details and links

Regarding efficiency of FDA, investigators and sponsors are all well aware that

PDUFA requires a timely turnaround for submitted data for marketing approval ...

in exchange for user fees.

See for details

http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/default.htm

(You might also refer to the Critical Path whitepaper for details on obstacles

to drug approvals.)

The main rate limiting factor for progress being the conduct of clinical studies

(particularly slow enrollment of patients in clinical trials), which would be

made worse by proposed legislation to approve drugs based on phase I safety

studies IMO.

Thanks for asking,

Karl