Life Science Compliance Update

July 22, 2015

FDA: "More Collaboration, Research Needed to Develop Cures"


The Food and Drug Administration's Deputy Commissioner for Medical Products and Tobacco, Robert Califf, recently offered his take on what is holding back medical progress. While a common critique is that the Agency's red tape is holding up innovation, Califf and an accompanying FDA report note that a "lack of understanding of the biology of the diseases" is to blame for the lack of treatment for Alzheimer's and many rare diseases.

"In these cases, the scientific community still lacks basic information about what causes these diseases and how they can be slowed and treated," states Califf. "When research does not offer answers to important scientific questions, cures cannot be developed. And when viable cures are not in the pipeline, focusing on regulation will not improve the situation, since FDA can only approve therapies with evidence for safety and effectiveness."

Califf writes:

Once key scientific questions are answered, we can use a variety of tools to reduce the length and cost of initial clinical trials for drug approval for these disease areas, and we can provide guidance to industry including advice on how to develop additional reliable biomarkers. For instance, we’ve improved the efficiency and predictability of clinical drug development by developing tools such as biomarkers and surrogate endpoints—markers of drug effect that do not directly represent an improvement in how a patient feels or functions, but are reasonably likely to predict a clinical benefit. Thus, for example, lowering a patient’s blood pressure can be used as a surrogate for the clinical benefit of preventing heart attack. Such tools have modernized clinical trial designs and may dramatically reduce the length and cost of drug development. They also can help target drugs to specific patients who can benefit most, thereby limiting the number and size of clinical trials.

An accompanying FDA report goes into detail about the state of drug discovery and development. for a number of diseases, starting with Alzheimer's (where "scientific discovery is in its infancy"), to diabetes (which is understood better than Alzheimer's, though scientific understanding is still lacking), to Hepatitis C (which now has a targeted therapy to prevent and treat the virus in specific patients). 

"While FDA has worked to transform the landscape for the final stage of drug development, progress in the discovery and testing stages of drug development has not kept pace," the report states. "As a result, too many diseases are still awaiting treatments and cures." View the report here.

Califf adds:

These are exciting times as we experience simultaneous revolutions in the biological and information sciences. We expect that the astounding increase in knowledge of biological systems enabled by whole genome sequencing, cloud computing, social media, and wearable devices to monitor physiology will create challenges to traditional thinking. And we are confident that this increased knowledge will continue to expand the pipeline of new therapies. This report emphasizes that we are prepared to deal with the product of this scientific investment by using regulatory paradigms that match the state of the science and by supporting dissemination of the latest knowledge applied to drug development.

The Agency will "continue to work to speed patient access to therapies shown to be safe and effective through our existing programs that allow for expedited review, development, and approval of certain medical products." In conclusion, he adds: "To encourage innovation, we also will continue to work with other government agencies and the healthcare community, including members of patient groups, academia, and industry. It will take a collaborative effort to improve our nation’s understanding of certain diseases and to translate any resulting scientific discoveries into cures."



July 15, 2015

FDA Communication Regulations Hurt Competition


We previously reported on Amarin’s lawsuit against the FDA, arguing that its restrictive interpretations of off-label speech would prevent the company from sharing “truthful and non-misleading information with healthcare professionals”. The lawsuit continues, and there has been significant back and forth between the FDA and Amarin on the issue, with oral arguments in early July. The lawsuit raises important questions about off-label speech and healthcare communications in general.


In an editorial by Dr. Scott Gottlieb at Forbes, the former senior FDA official discusses the negative impact of FDA labeling regulations on prescription drug competition and patient health. Over at the Pharmaceutical Research and Manufacturers of America’s (PhRMA) blog, Catalyst, they raise an interesting point: as HHS and other stakeholders dedicate themselves to shift U.S. healthcare to a system rewarding value-based care, is that aligned with biopharmaceutical companies’ ability to support this shift to value? Especially when FDA regulations specifically limit the companies’ ability to communicate information like cost effectiveness data on approved treatments when the information is not included in the package insert approved by FDA?


Gottlieb notes that valuable economic information, like uncontrolled observational studies, cannot be shared by manufacturers, regardless of the quality of the study. This results in less incentive for manufacturers to develop this data in the first place. Gottlieb cites a survey conducted by Avalere Health, indicating how much current regulations dissuade drug makers from developing information they cannot promote or speak about.

The study found that 86% of pharmaceutical companies indicated they would invest more in studies to support the development of healthcare economic information if provided additional guidance on their ability to use this evidence with external audiences. This information could then be used to help payers and providers make treatment decisions.

Proposed changes in the 21st Century Cures legislation are intended to provide clarity around the evidence manufacturers can communicate with payers and decision makers about the value of products. Avalere suggests this may “result in better evidence on cost-effectiveness, comparative benefit, and real-world outcomes for payers determining patient access to these medications.”

Currently, laws and FDA regulations govern pharmaceutical company communications to physicians and consumers. Companies’ clinical claims must be substantiated by two well-controlled trials, provide fair balance, and be consistent with FDA-approved labeling regulations. Additionally, Section 114 of the FDA Modernization Act sets different standards for how health economic evidence may be presented to payers. Without additional guidance, permissible evidence and possible audiences for communication may be left out due to varying interpretations of the law across the industry.

“Setting aside the question of whether the current rules restricting this speech are constitutionally permissible, or violate First Amendment protections, the fact is that the rules and enforcement chill the free exchange of health economic information,” writes Gottlieb. “Drug companies can only make claims around benefits, and usually relative to a placebo. As a consequence, resources are plumbed into trials that will enable the kinds of information and results that government rules allow drug makers to share.”

This results in a less competitive market because there is less data and information reported, skewing debates about relative value. Ultimately, manufacturers cannot put forward data that argues the true value of their product, whereas, those with “economic incentive” to control access can do so, writes Gottlieb. He also notes Section 6301 of the Affordable Care Act’s specific instruction to government agencies to disseminate research “with respect to the relative health outcomes, clinical effectiveness, and appropriateness of … medical treatments [and] services.”

Supporters of the Affordable Care Act note that physicians often practice medicine without knowing the comparative effectiveness of medical interventions. For instance, one of the leading medical textbooks writes that it is not known whether drug treatment works better than removing certain heart cells to treat a common type of heart arrhythmia. While comparative effectiveness research is conducted in other countries, it is less prevalent in the United States. The purpose of the Patient Centered Outcome Research Institute (PCORI) was designed to fill this research gap. Gottlieb points out PCORI “creates the strange specter of the federal government funding the creation of information that the feds then bar certain parties from speaking about,” as PCORI creates standards for the conduct of real-world evidence studies and other trials that likely will not meet FDA standards, including system reviews and observational studies.


Gottlieb concludes by reminding policymakers they want cost and value to be factors in how decisions are made in American healthcare. “Should they be comfortable with a landscape where sponsors are discouraged from generating this data about their products, and as a consequence prohibited from competing on these important domains? Or where the information and speakers are biased in favor of one side of that debate?”

A lack of information reduces competition which leaves the patient and their physician with less information to make informed decisions. If we want greater value in the pharmaceutical market, more information is one way to start.



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