Life Science Compliance Update

July 05, 2016

Bipartisan Policy Center Holds Briefing on Health Innovation

At a briefing hosted by the Bipartisan Policy Center (BPC), Senate Health, Education, Labor, and Pensions (HELP) Committee Chairman Lamar Alexander confirmed that negotiations over the Senate "Innovation Initiative" are still underway. Senator Alexander noted that the Committee is "in the midst of discussions" with House Speaker Paul Ryan and Senate Majority Leader Mitch McConnell on how to advance the package.

Specifically, Senator Alexander highlighted a conversation he had with Senator McConnell, where both senators agreed that the medical innovation package could possibly be "the most important legislation that Congress acts on this year."

In his remarks, Chairman Alexander described the Innovation Initiative as a proactive investment to help cut down healthcare spending, citing the forward-looking success of President George W. Bush's President's Emergency Plan for AIDS Relief (PEPFAR) in helping to control the HIV/AIDS epidemic abroad.

Senator Alexander highlighted the need for a smooth transition to electronic health records, as precision medicine will not work without using advanced health data. He does not believe that the federal government's investment in EHR has not been spent very well, and that Congressional leaders are working together to help ensure future efforts are more efficient.

Senator Alexander addressed the critics of the Innovation Initiative, stating that the Senate needs to take steps to "make sure the horror stories don't derail the success stories."

Senator Alexander also used his time to highlight other issues, including combating the opioid abuse epidemic and how to improve opportunities for Americans to be treated with regenerative medicine.

New BPC Report

In connection with the briefing, the BPC published a new report, "Using Real-World Evidence to Accelerate Safe and Effective Cures." The report provides a set of recommendations on improving the use of data in data development and strengthening the Food and Drug Administration's (FDA's) ability to oversee the progress.

The recommendations focus on different ways the current drug development process could be modernized and improved through the use of real-world evidence, as well as policy action suggestions to implement those suggestions.

Among the proposals are measures to: improve the medical product development process, increase regulatory clarity, use health information technology to improve health care, and increase investment in medical products to address unmet and public health needs.


The recommendations are as follows:

Recommendation I: Improve Regulatory Clarity Regarding Use of Real-World Evidence

Current evidence requirements date back to 1962, when amendments to the Federal Food, Drug and Cosmetic Act (FDCA) included provisions requiring manufacturers of drug products to establish a drug's effectiveness by substantial evidence and adequate and well-controlled investigations before it could be approved for marketing. Since that time, several regulations and guidances have been published.

Included in the policy ideas for this recommendation were suggestions that the FDA should: develop formal guidance regarding the use of real-world evidence to inform regulatory decision-making, including the circumstances under which real-world data could be used as well as the types of real-world data, methods, and the levels of evidence that would be acceptable for use in regulatory review and decision-making. The guidance should include, but not be limited to, new drug approvals (including approvals under expedited programs), label expansions, new indications, post-market commitments, and post-market study requirements; and engage representatives of regulated industry, patient and disease research organizations, academia, experts in the use of electronic data, experts in statistical methods, and experts in privacy policy in the development of the guidance.

Recommendation II: Improve Methods and Data Quality for the Generation and Use of Real-World Evidence

The scope and amount of real-world data potentially available is rapidly expanding, as are the methods to effectively use and interpret the data for regulatory decision-making purposes. The methods and interpretations that have traditionally been used may not be the most appropriate methods to use for understanding larger data sets, or data drawn from across a network of disparate databases. It is therefore imperative that regulatory agencies and others who rely on the data educate themselves about best practices in methods of use and interpretation of real-world evidence for decision-making purposes.

This recommendation included suggestions for both the FDA and HHS, including:

  1. the FDA should establish a program to promote sharing and evaluation of methods used in the evaluation of real-world evidence for regulatory decision-making. The FDA should invite a broad spectrum of researchers who are active in the generation and use of real-world evidence and methods development, as well as leaders who rely upon such real-world evidence—including regulators and payers—to participate in this program.
  2. The U.S. Department of Health and Human Services (HHS) should support research to improve methods for the use of real-world evidence, which take into account the much larger samples of electronic data now available and enable high-throughput methods that produce accurate and well-calibrated inferences that quantify levels of uncertainty more accurately. Such research should focus on issues that include, but are not limited to, mitigating bias, obtaining solutions to better refine outcomes definitions, understanding implications to analyses for integrating observational data across a number of disparate sources, and understanding the contributions of real-world evidence to causal reasoning.

Recommendation III: Improve Policies for Information Sharing to Support Clinical Research

Under current law, in order to conduct one real-world study across multiple health care systems, multiple institutional review board (IRB) approvals are required. Given the differences in how IRBs view their remit and what constitutes a clinical trial, a unique and individualized approach is often needed to seek approval from each, which can lead to delays in trial execution and increased costs.

In light of that, two suggestions were made to Congress, including the idea that Congress should require the HHS Secretary—through the OHRP and the FDA—to issue regulations and guidance to facilitate the broader use of centralized IRBs within 36 months, by clarifying the roles of IRBs in multi-site studies and the risks and benefits to human subjects, standardizing informed consent, and incorporating community values through the use of local IRBs while continuing to use central IRBs.

Recommendation IV: Explore New Adaptive Pathways to Modernize Drug Development and Support a New Era of Personalized Medicine

As medicine continues to become more personalized and drugs become targeted for smaller populations, traditional, large-scale RCTs will become increasingly less feasible and additional approaches will be needed to assure safety and efficacy and protect the public's health. Rapid advances in technology and personalized medicine will allow for more-close monitoring to be easier, cost effective, and accurate. To advance the exploration of a new, more flexible adaptive approach to drug approval, several steps must be taken.

Included in those steps are the following suggestions:

  1. The FDA should develop a new program to develop and test a new adaptive pathway approach to expand the capacity for drug development that has the following key attributes: iterative phases of development, beginning with initial marketing authorization to a restricted patient population, then expanding to wider populations based on risk-benefit ratios; gathering evidence through close-monitoring and other real-world evidence, to supplement RCTs; and early involvement of stakeholders who have a role in determining patient access to the drug, including industry, payers, regulators, clinicians, and patients.
  2. The FDA's new program to develop and test a new adaptive pathway approach for drug development should include the following elements: qualifying criteria for the program, which will determine which types of drugs at what stages could be considered for the adaptive pathway approach; types and levels of evidence required for initial approval and expansion, including evidence generated from close-monitoring, other real-world evidence, and randomized controlled trials, as appropriate; methods for early involvement of patients, clinicians, payers, industry, and regulators; and methods for assuring market removal or label modification of products when follow-up studies and monitoring are not completed or when an unfavorable risk-benefit ratio for certain populations is demonstrated.


February 16, 2016

Senate HELP Committee Moves Closer to Creating Corollary to 21st Century Cures

Last week, the Senate Health, Education, Labor, and Pensions (HELP) Committee approved a series of seven bills to work up medical innovation legislation that will eventually likely become the Committee's response to the 21st Century Cures Act passed by the House of Representatives.

Last month, HELP Committee Chairman Lamar Alexander of Tennessee estimated that the Senate's version will not mirror the House bill, and that the Senate's effort will focus on priorities that are identified by the Committee's members, such as improving federal electronic health record programs.

Last week's productive meeting was not the last meeting for the Committee on this topic, either. The panel is set to consider approximately twenty pieces of innovation-related legislation, and there are meetings set for March 9, 2016, and April 6, 2016.

During Chairman Alexander's opening statement last week, we saw a preview of his expectations for the process of how to move the innovation bills through the panel all the way to the Senate floor. He emphasized the bipartisan nature of the fifty proposals included in the twenty bills, and that he would personally ensure that consideration of each proposal would include an opportunity for debate and open amendment. Chairman Alexander is hoping that he can work to create a consensus on the measures while they are in the Senate panel, holding off the contentious debates until they reach the Senate floor.

The Advancing Targeted Therapies for Rare Diseases Act of 2015

This bill aims to speed up the approval process of genetically targeted drugs by allowing companies to use evidence from already-approved drugs. As per the text of the bill, this legislation would "facilitate the development, review, and approval of generically targeted drugs to address an unmet medical need in one or more patient sub-groups (or gene variant subpopulations) with respect to rare diseases or conditions that are serious or life threatening; and maximize the use of scientific tools or methods, including surrogate endpoints and other biomarkers for such purposes." This approach is different from the 21st Century Cures Act in that the 21st Century Cures bill would provide a six-month extension of exclusivity periods and patent protection for an already-approved drug if the sponsor works to obtain approval for a new indication for either a rare disease or rare condition.

The FDA Device Accountability Act of 2015

This bill is similar to the 21st Century Cures Act and attempts to eliminate "burdens" that are slowing down the FDA's consideration of new, innovative, medical devices. This bill asks for FDA reviewers to use least burdensome requirements in their review, permits centralized, non-local institutional review boards for device trials, and also requires the FDA to update their guidance on Clinical Laboratory Improvements Act (CLIA) waivers. The Senate goes further than the House, however, by allowing reliance on post-market information for premarket approval devices as part of the least burdensome requirements.

The Next Generation Researchers Act

This bill works with the NIH and establishes a Next Generation of Researchers Initiative, where policies and programs would be coordinated to promote and provide research opportunities for new researchers and work to give researchers earlier independence. The legislation also calls for the National Academy of Sciences to study and report on the barriers that are likely to be faced by the next generation of researchers, the impact of sequestration and federal budget constraints, and recommendations for ways to improve entry into, and sustain careers in, research.

The Enhancing the Stature and Visibility of Medical Rehabilitation Research at NIH Act

This bill calls for the National Center for Medical Rehabilitation Research (NCMRR) to develop and update a research plan for medical rehabilitation research. Under this bill, the NCMRR is also required to annually report on the progress of achieving the objectives, benchmarks, and guiding principals described in the research plan. The bill mandates HHS enter into interagency agreements to better coordinate medical rehabilitation research.

The Advancing Research for Neurological Diseases Act of 2015

This bill amends the Public Health Service Act to require the Centers for Disease Control and Prevention to enhance and expand infrastructure and activities to track neurological diseases. The bill also mandates that CDC incorporate that information into a National Neurological Diseases Surveillance System, and requires that HHS provide for the collection and storage of information on neurological diseases, including incidence and prevalence rates, to the extent practicable.

The Preventing Superbugs and Protecting Patients Act

This bill mandates that the FDA publish a list within six months following enactment of a reusable device that would need to provide proposed cleaning instructions as part of a 510(k) premarket submission. The devices on the list would also be required to provide the FDA with the validation data that shows that the proposed cleaning instructions are sufficient for safe cleaning, disinfection, and sterilization of the devices between patient use.

The Improving Health Information Technology Act

This bill scrapped an earlier plan of setting up a new health IT committee to replace current committees. This proposal eases requirements on physicians who enter data into electronic health systems by permitting nurses and other healthcare provider teams to enter and document the information as well. The bill also establishes a rating system for health information technology to help professionals in choosing products and facilitating information sharing between providers. This most recent draft also strikes fines and compensation fund found in earlier proposals.

These bills are a start for the Senate to work towards a companion bill to the House 21st Century Cures Act. We will monitor the Senate's progress and try our best to keep our readers abreast of any developments.

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."




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