Conflicts of interest at FDA must be confronted

OPINION:

The Food and Drug Administration is a Jekyll-and-Hyde agency that regulates 20 cents of every dollar American consumers spend. It has many strengths: Its line employees tend to be bright, educated and committed to the agency’s mission. Despite those strengths, it ignores ethical blind spots and refuses to rationalize its tangle of regulatory and administrative requirements.

These failures are predictable products of the FDA’s culture and the leadership imposed by Washington insiders. No group has been more powerful in selecting commissioners than Ralph Nader’s Public Citizen, which for decades has convinced the executive and legislative branches that experience in a regulated industry is disqualifying for senior appointments at the FDA.

As a practical matter, this standard has largely limited the pool of potential commissioner candidates to medical school professors. Although it once reduced conflicts of interest, for at least three decades now, any candidate with the expected academic pedigree for the commissioner’s post has had many lucrative private sector contractual relationships.

The Public Citizen influence also means that commissioners typically take on a huge management challenge with no management experience and thus rarely try to make the agency more efficient, flexible, transparent or courteous. With the supervision of FDA senior employees so lackadaisical, they become largely unaccountable and perpetuate a culture similar to that of medieval fiefdoms and the National Institutes of Health.

This lack of accountability undermines the agency’s public health mission. An examiner for a small, obscure part of the agency once told me that he would ignore all relevant written regulations for approval of my company’s product and impose a far higher standard that he would share only orally.

I learned later that he was angling to move to the private sector by generating data Big Pharma wanted. He was short-tempered when I said I would appeal to higher-ups, and later that day, I got a call from the long-standing head of that subagency, who spewed obscenities at me for more than a minute before hanging up.

It would be beneficial for commissioners to have been on the receiving end of such experiences. Executives with that background would better understand why good management and questioning self-defeating orthodoxies are important.

The next commissioner should begin by reviewing the advisory committee structure. It exists largely for show, because examiners believe no one is better equipped than they are to make decisions on approvals. They routinely manipulate their advisory boards with the information they provide, and there is rarely real disagreement between an advisory board and the agency. The spectacle does provide cover for controversial decisions, but the process is extremely expensive, delaying approvals by many months.

The situation is worse than that, though. Few major academics had significant private sector contracts when the FDA instituted its advisory committee infrastructure. Now, the world is completely different. Almost every significant medical school professor has multiple lucrative arrangements with industry, but the FDA has ignored that problem for decades.

I once went to a senior FDA official to object to an advisory committee stacked entirely in favor of a competitor. He listened patiently, shrugged and said, “OK, you can knock off the worst two.” Public Citizen, of course, is silent about those conflicts.

It is essential to remove compromised input from the product approval process and restrict academic advice to broad guidance that might improve the agency’s regulations and processes.

For instance, the clinical trial requirements for a new class of products are usually unclear until hundreds of millions of dollars of unnecessary spending and years of delay have already occurred; an advisory committee could help in that area. Similar issues must be resolved for the agency’s regulation of medical devices, food and other industries.

An ad hoc advisory committee should also examine the clinical trial requirements for post-approval confirmatory trials. The agency’s attachment to placebo-controlled trials makes sense for most investigational trials, but once a drug is approved, withholding an effective treatment is ethically problematic. It might help to require an annual refresher class about the Tuskegee syphilis study and other ethical disasters of medical research.

The FDA is also consistently behind the curve when new diseases emerge, such as Ebola. It could also do more to encourage the repurposing of safe, biologically active drugs that fail efficacy targets; tens of billions of dollars go to waste each year because the culture of Big Pharma encourages business development executives to bury their disappointments rather than let them succeed elsewhere.

It is time for a change.

• Michael Astrue is a former commissioner of Social Security, general counsel of the Department of Health and Human Services, biotechnology CEO and chair of the Massachusetts Biotechnology Council (now MassBio).