Live Blogging from FDA in the 21st Century Conference, Panel 1: FDA in a Changing World

[This is off-the-cuff live blogging, so apologies for any errors, typos, etc]

Panel 1: FDA in a Changing World: Lewis Grossman, Ted Ruger, Barbara Evans, moderated by Holly Fernandez Lynch

Lewis Grossman, FDA in the Age of the Empowered Consumer

Begins his analysis by comparing a hypothetical consumer in 1960 and today.

Consumer was passive. Today’s consumer is active, more unmediated choice, more direct citizen involvement.

Why the change? 1970 was the decade of advocacy, culminating in 1972 Patient’s Bill of Rights from AMA. Central them was informed consent and thus complete information from physician.

1998 saw disruption of WebMd and now even more disrupted by web search technology which is how most patients get there info.

Food: 1966, recipe standards. Relatively little variety and consumer choice. Very little info on  nutrition, “batman white bread.” Turning point was 1969 White House conference that led to more choice and more info.

Health clams as the portal where 1st Amendment law entered into FDA law. The image of the intelligent consumer who need not be shielded from information.

Changes in standard by which FDA decided if something was misleading. Until 2002 unsure if reasonable or gullible consumer standard. In 2002 for food FDA chose the reasonable consumer standard.

Liberal and conservatives got scrambled on these matters in interesting ways.

Also a revolution in advertising, leading to revolution of patient’s relationship to his or her drugs.

Various citizen movements. Laetrile in the 1970s, HIV crisis in 1980s.

Rise of empowered consumer is something FDA will have to continue to reckon with. 2012 FDASIA added new section to FDCA about patient consideration and views being solicited by the agency.

Ted Ruger, After the FDA: A Twentieth Century Agency in a Postmodern World

FDA has adopted a technocratic focus on some variables.

Ignored other issues like how we consume food and why as well as comparative effectiveness research that are becoming more important in public health and health care.

Requires either a change in FDA’s priorities or FDA sharing the regulatory stage with other institutions.

As Peter Hutt said FDA is mostly about regulating things and words about things. But it is this product specific focus that has defined FDA for the last 50 years and may be ill-suited for the future.

Upton Sinclair’s book the Jungle was a critic of this focus of FDA all the way back in 1906. We have a food supply that is very safe for our stomachs, not so much for our heart. FDA has focused on disembodied food safety but not how we consume it that has led to some problems of public health.

Turning to therapeutics. The shape of medical authority has changed. From 1960 to 2000 we had a centralized FDA and diffuse regime of prescribers. This was good for FDA and patients, in that FDA had clear ascendancy and no other rival for setting standards, clearly promoted patient choice. But also promoted increased costs for health care because of this diffusion. The future is more of these decisions being made by payers at a centralized level, Medicare, Medicaid, and insurers creating boundaries and incentives in terms of what is reimbursed. FDA no longer being the single gatekeeper. Now two step, FDA approval will be one step, and reimbursement approval as the second. There was a certain egalitarianism in the old regime. If FDA did not approve it, no one could buy it. And from 1960-1990s if you had OK health insurance most people had relatively equal access to such products. That is not the world we are in or entering.

What does this mean for the FDA? I thought I would be saying FDA needs to adopt these changes. But I now think that the better model is a two-track model, where FDA does what it does best but other agencies do some of the other functions.

Barbara Evans, The Future of Prospective Medicine Under the Food and Drug Administration Act of 2007

The new thing is prospective medicine. Keep people healthy and extend life. But the end of life at age 120 will be the same, we will be in the ICU with tube up our nose.

All the problems with Randomized Clnical Trials premarket get worse for prospective medicine.

Prediction is only useful if actionable. Screening colonoscopies? The hope is we will have a drug to help you make the protein you are missing. Very hard to show that will be effective. A benefit over a very long time frame. A 50 year clinical trial where you show that you will be healthy? Many of these preventative uses will be off-label, a statin that may be off-label. That which can be approved will be approved through surrogate end points. With prevention you are putting drugs into people with nothing wrong with except a predictive risk. Our tolerance for safety concerns will likely be worse.

One result will be that in postmarket world there will be not just cloud of safety issues but also effectiveness.

In 2007 major amendment to FDA Act, the FDAAA, inspired by IOM report.

Establishes a hierarchy of when FDA can call for a postmarket study.

All of these techniques are predicated on “serious risk.” Does that apply to efficacy or just safety? One element of definition of “adverse drug experience” include “any failure of expected pharmacological action of the drug” that she reads as encompassing efficacy. That would include reduced benefit in ration to harm that it was thought for approval. It could also mean more non-responders than we thought.


HOLLY LYNCH: Can we think of food serving sizes as like dosages? Drugs for prophylaxis as analogy?

GROSSMAN: In food arena almost completely empowered consumer. In area of drugs more engagement but not complete empowerment. AIDS movement responsible for fast track and approval. View of risk benefit not a complete scientific but a policy decision. To degree the doctor cut out completely that is consumer empowerment.

RUGER: In 21st century there will be regulation through payment. FDA has been disinterested in use. FDA is the agency that’s conception of its own use derives from the commerce clause power pre-Wickard Supreme Court decision about aggregation. This is why FDA’s statutory authority is so limited. Could not go after behavior because child labor law was unconstitutional in the era. That is why so much of its early cases are in rem cases. Path dependence.

EVANS: No sharp line between curative and preventative, if you cut your foot and get a drug and don’t get gangrene?

PATRICK LEARY: Concerns about funding and getting approved?

QUESTIONER: Accuracy of web info?

RUGER: Drugs where companies did not push drugs to market because of fears of non-reimbursement. More pronounced in Europe where there are two tracks. Extent to which one is concerned will depend on whether you think it is optimal not to reimburse and why?

GROSSMAN: Under central Hudson framework can definitely ban drugs that are false and misleading, labeling advertising, etc. Only thing FDA can really do is combat inaccurate info with accurate view.

CHRIS  ROBERTSON: Concerns about insurers rationing care. To what extent are we already seeing this vs a future direction. Avastin?

RENA CONTI: Idea that FDA has imperative to assess effectiveness of already improved drugs. What are the infrastructure and capacity of existing FDA for data infrastructure to require and compel both manufacturers and payers to provide that info to the FDA.

RUGER: Soft power approach to encourage generic or cheaper alternative. Unusual flattening of cost curve in the last few years but predicted to evaporate. One might predict that where times get tougher economically more formulary exclusion. Problems of horizontal equity and transparency.

GROSSMAN: Target may not be FDA but other agencies. Think about Avastin that Abigail Alliance and other patient advocacy pushed for initially lost. Not approved for breast cancer. But then one, off-label usage for it. And CMS still covered it after all!

EVANS: Sub-grouping as a possibility in post-market world, esp when effectiveness and safety change for a sub-group for whom it does not work. Skeptical that manufacturers will have access to data it needs to do those studies but a manufacturer may face HIPAA and other problems although FDAAA lets FDA-corp partnership.

GLENN COHEN: Long clinical trial for preventative medicine? Intellectual property?

EVANS: Long clinical trials are not financially effective or may not be ethical to deny control arm the therapeutic going forward. So we will have to do observational studies instead.