Harvey W. Wiley Lecturer Speeches

2015

Remarks by Michael Taylor, 2015

It's an honor to be awarded a prize named after Harvey Washington Wiley, the man who created a "poison squad" composed of civil service volunteers who got free lodging in exchange for eating poisoned and adulterated food. I'll certainly take a close look at my lunch today.

Wiley's idea was to demonstrate that substances that were commonly used in commercial foods at the turn of the twentieth century, like borax and formaldehyde, were harmful.

Wiley had the luxury of operating in an era before IRBs, but he had to contend with another pest that afflicts today's researchers – and FDA: the press.

Wiley, chief of chemistry at the agriculture department, was greatly irritated by the media's interest in his poison squad experiments and he tried unsuccessfully to prevent newspapers from reporting on them prior to completion of his hundreds of pages long scientific manuscript. When he blocked access to the test subjects, reporters simply made up stories.

Of course, probably not even Wiley's own mother read his manuscript, but the newspaper articles caught the public's imagination. Vaudeville songs were written about Wiley and his valiant guinea pigs. About the same time, Upton Sinclair wrote a book that he hoped would persuade Americans to adopt socialism. Instead, The Jungle, along with reporting on Wiley's poison squad, persuaded Congress to pass the Pure Food and Drugs Act in 1906, creating the FDA – and Wiley was appointed to lead it.

I don't go back to Wiley's time, but I've been covering the FDA and Washington beat a long time. BioCentury has given me an opportunity to investigate and report in print on the intersections of policy, politics, science, and business for a little over 20 years. We've been doing the tv show since September 2010; it has given us a fantastic ability to communicate about topics like those that are being discussed at today's meeting to a broad audience. I spoke with another FDA hero for our very first show, Frances Kelsey, and interviewed Mary Pendergast and Bob Temple about the risk-benefit thinking involved in bringing Thalidomide back as a treatment for multiple myeloma.

I want to talk today about some of the things my colleagues and I have observed.

It is continually surprising how insulated the individuals engaged in discovering, developing, regulating and paying for new medical therapies are from each other. With a few exceptions, biotech and pharma CEOs are making decisions based on astonishingly inaccurate perceptions about FDA. Many or most people at FDA don't understand the motives, constraints, and realities of the companies they regulate. There are similar chasms of understanding when it comes to academics, payers and patient groups – and how many members of Congress have a deep understanding of the topics we're discussing at this meeting today, issues that affect the health of every American and the country's economic competitiveness?

Greater understanding among stakeholders isn't a vague or idealistic goal. The purpose is to find ways to work together to create new models of drug development. There are a large number of practical experiments being conducted today to do just that. These experiments are long overdue: innovation applied to the business and regulation of drug development has lagged far behind scientific innovation.

I'll briefly mention a few of these experiments. Many of these experiments are driven by frustration with a model that leads to what BioCentury calls the "duplication of futility" – multiple organizations working in parallel, in secrecy, often for years, only to discover that they have been traveling down a dead end. This isn't just bad for business, it is bad for patients.

Important to note that many smart people who read and watch BioCentury think these experiments are a waste of time. They may be right – they are experiments, so they might not succeed. But they have to propose something else, because today's pace – getting two or three drugs with novel mechanisms of action approved a year – isn't good enough. And it isn't good enough to say it is all FDA's fault.

The example of patients, clinicians, regulators, drug companies coming together to address the AIDS crisis shows what can be done. One result was a regulatory innovation – accelerated approval – that has literally saved and extended millions of lives. The surprising thing is that the AIDS experience hasn't been replicated.

  • I-Spy 2. A trial of drug candidates in the neo-adjuvant breast cancer setting. Adaptive: researchers learn during the trial. Each woman benefits from the experience of those who went before her, and contributes to those who come next. Incorporates prospective study of biomarkers. An ongoing screening protocol. Initial test products from Abbott, Amgen and Pfizer. Will graduate to Phase III or be dropped. Can be replaced – no need to get new protocols approved, etc.

  • "Open innovation" experiments. Archipelago to proof of clinical mechanism led by Aled Edwards. Patent-free development through Phase II. Directly aimed at duplication of futility issue.

  • Venture philanthropy. The Kalydeco story. Patient groups driving and funding highly targeted R&D conducted by academics and industry. Keys to success: CF Foundation very actively manages R&D, doesn't simply fund it. Also created a clinical trial network and disease registry. Multiple myeloma research foundation.

  • Critical Path: a huge amount of experimentation inspired by FDA's 2004 Critical Path report. Gandhi's joke about western civilization (good idea, why not try it?). Haven't delivered on the promise. Scientific opportunity, urgency and scale are the three drivers of life sciences regulatory innovation…. The science is moving fast, but in the U.S. there hasn't been urgency or scale… also a failure to make a business case and execute on it.

  • IMI. Public funds matched by private in-kind investments, industry-driven translational research.

  • Translational science. Low hanging fruit: There's a huge opportunity to mine FDA's data about what doesn't and won't work and disseminate that information to promote drug development. Need to get agreement to turn today's assumption that everything in drug development is secret unless there is a requirement to make it public on its head. The Critical Path Institute has taken some steps in this direction – a pilot scale. NCATS – addressing the right problems, but far from clear sufficient resources will be devoted to it, that it will be a priority after Collins leaves, or what it can contribute. Again: a business case needed.

  • Emerging models for patient-driven regulation (incorporating patient perceptions of benefits and risks into decisions about endpoints, subpopulations, etc.). Areas where this could break logjams include obesity and diabetes.

  • CER. Politically correct term is Patient Centered Outcomes Research. Maybe there's too much political correctness. No one could argue with the need to develop better data about what works and what doesn't work, and for who under what circumstances. But the excruciating process PCORI went through just to define its mission.. Collins threw up his hands… and its failure to clearly explain what it is going to do with

  • Place where there is the least experimentation and the greatest opportunity: collaboration between payers, drug developers and academia. Merge low-cost gene sequencing data and electronic medical records. Create a system where every patient's data contributes, and where physicians can apply research at the bedside. Advances possible when clinical trial participation increases (pediatric cancer example).

There is no way to predict with certainty which, if any, of these experiments will work. But one thing can be predicted with absolute certainty: if nothing new is tried, things won't change. If you're satisfied with a 15-year and growing gap between discovery and approval of a product, ever-increasing development costs, and regulatory uncertainty chasing away investment in life sciences, that's fine. But if you think, as I do, that patients deserve better, we need even more experimentation.

After all, that's how FDA got started – with Harvey Wiley's experiments.