FDA's Margaret Hamburg: Angle on Patient Engagement and Regulatory Systems Reform

While at the 2014 New York BIO conference, FDA Commissioner, Dr. Margaret Hamburg, had the opportunity to address pressing issues affecting the biopharmaceutical industry and the FDA.

Margaret Hamburg’s Position on Patient Engagement

The FDA is committed to a new initiative called Patient Focused Drug Development and we really do believe that drug development in our review process could benefit from a more systematic and expansive approach to obtaining the patient’s perspective.  Over the past year, we held public meetings on diseases including chronic fatigue syndrome, lung cancer, HIV, and narcolepsy. These sessions have allowed us to directly interact with patients, patient advocates and caregivers about the severity of the disease, current treatment options, and the impact that these diseases have on patients’ daily lives, as well as the actual patient experience with currently available treatments. We believe this program will provide a better and more informed understanding of these diseases, which really can help us find ways to develop new and better treatments, and more effective user-friendly medical interventions.

Hamburg’s Perspective on Adaptive Regulatory Approval Pathways

I want to underscore that FDA does not use a one-size-fits-all approach in product development. We tailor programs to the specific product, and the condition of the treatment. This is something that is very important and something that I am proud of, although interestingly, we are being criticized.  

It would be a terrible thing if we required the same approach for every single disease and every single product that came before us. But, it is essential that we have a more flexible approach, and it is clear that it is reflected in much of the work we do.  For example, FDA routinely approves orphan drugs based on non-traditional drug development programs.  A study published in 2012 by the National Organization for Rare Disorders found that two-thirds of the non-cancer orphan products approved between 1983 and June 30, 2010, were based on single trials, studies using historical controls, and other strategies. Consider some recent approvals; Imbruvica, a treatment for mantle cell lymphoma, was approved based on an open label single arm trial, which means that every patient received the treatment and both patients and researchers knew they were receiving it. The results were compared on how well the 111 participating patients had responded to previous treatment for the rare disease.  Elelyso, an orphan drug approved in 2012 for Gaucher disease was based on two trials of 56 patients. Though we allowed different supporting data to approve these drugs, the underlying goal and responsibility was the same -- to help translate the newest discoveries and research into treatments for patients who need them – and to do this in the most efficient and effective possible way while ensuring that rigorous standards for the assessment of safety, efficacy and overall benefit to patients are met.

 Hamburg’s Opinion on Adaptive Trial Design and Study Standardization

An important focus has been on developing innovative and adaptive clinical trial design. One example is Enrichment Trial Design; about 18 months ago we issued guidance that spells out how researchers and drug developers can use clinical trial enrichment to greatly increase the likelihood that data collected during a clinical trial will demonstrate whether the drug is effective. These are potentially very powerful strategies for the pharmaceutical industry and scientific communities because appropriate use of enrichment could result in smaller studies, shortened drug development times, and lowered enrollment costs. Enrichment won’t save a drug that doesn’t work, but, it will help find why it does.  Drugs that treat cystic fibrosis, cancer, and other diseases have come to market using this approach.

Another highly innovative approach in clinical trial design is the recently announced the

: a collaboration amongst FDA, patient advocacy groups, academia, and the drug industry.  This study will test multiple new investigational drugs with multiple study arms at multiple sites using whole genome sequencing to screen the patient population for a wide array of genetic traits so that patients will be matched to the treatment regiment, and so they can slow their cancer as soon as possible based on the information. Not only does this program offer novel clinical trial design, and new hopes for patients in the area, but it also establishes a platform and an approach for ongoing clinical trials in this area and in others.

Hamburg’s Mindset on Improving Clinical Trial Infrastructures and Regulatory Science

We are working closely with stakeholders to advance innovative clinical trial design to many other areas; oncology is an area that is very active, but, also in areas like the development of new antimicrobial products, which is so important to treat patients and regress the growing problem of antimicrobial resistance.  We are sponsoring a workshop, FDA and NIH together, to discuss streamlined regulatory pathways and the potential use of common clinical trials to expedite development in this area.

We think that there is a lot of merit in supporting improvements in the clinical trial infrastructure itself.  The Clinical Trials Transformation Initiative has contributed so much in terms of innovative trial design, as it is working on establishing centralized IRBs for multicentered trials, which is an important advancement.

Hamburg’s Advice for Start-Up Biopharmaceutical Companies

We recognize a few clear issues: the importance of engagement, transparency and communication with all of our stakeholders. Importantly, through our efforts to encourage early interaction with, and offer support and directions to developers of medical products, it’s clear that we can now reduce the cost and improve the success of earlier phases of development and ultimately offer much-needed products to patients.  In fact, these early meetings can save years in drug development by helping companies identify what studies to conduct, which aren’t needed to define endpoints and goals of the development program, and to reduce costs.

We recently examined new molecular and biologics entities that were approved between 2000-2013, and found that sponsors that met with the FDA early in the process, especially prior to filing an investigational new drug application, were likely to have a shorter clinical development time for their product. Those who participated in pre-IND meetings had a median clinical development time that is approximately 2 years shorter than those without. I think it is particularly important for small companies who are less likely to be familiar with FDA’s approval process, and are less likely to even think about requesting these early-stage meetings. It is exciting to see how working more closely and earlier with companies we can help speed the development of some drugs and more quickly work to bridge the gap between scientific discovery and the real-world products and processes that can make a meaningful difference in people’s lives.

Moreover, because of the position FDA occupies in the development process we have a unique ability to see what’s in the pipeline – as well as what is not but in fact is needed to address unmet medical and public health needs. We also have a keen understanding of what it takes to translate good ideas into viable products for both development and manufacturing and can encourage companies to undertake these efforts.

Hamburg’s Vision for Innovation at the FDA

I have been a vocal advocate for the importance of investing in developing a new focus on regulatory science, and by this I mean the knowledge, tools, strategies, and approaches that will enable us to more efficiently and meaningfully assess product safety, efficacy, quality, and performance, and can reform product development in an important new way.