By Dr Nicola Davies
In recent years, the US Food and Drug Administration has taken several steps to better position itself to support medical innovation. Still, the director of the Administration’s Center for Drug Evaluation and Research (CDER), Dr Janet Woodcock, has recently criticized certain research practices that she feels frustrates the progress of innovation. Praising the quality of the science, she notes that it is just not enough, reminding researchers of the ultimate goal – to improve human health, not just obtain FDA approval. 1
Where medical innovation falls short
When Dr Woodcock spoke with researchers from universities, research institutes and pharmaceutical companies at the annual ‘Breakthroughs in Medicine’ conference in Los Angeles on September 6, 2019, her focus was on the very high costs of innovative and breakthrough drugs. In particular, she criticized the current structure of academic research, which discourages collaboration between researchers. She argued that corporate secrecy during the process of creating and commercializing a drug is a significant reason drug trials are fragmented and costly. She also criticized the tendency of researchers to steer clear of studying important aspects of a drug when there is no clear commercial gain. 2 So, how is Dr Woodcock suggesting medical innovation be propelled? She has urged researchers to leverage big data sources such as electronic health records to develop wider-reaching treatments. She has also suggested that practicing doctors be involved in the research process. Generally, a lot of changes need to be implemented in the scientists’ relationships with regulators, doctors and one another if recent advances in medical innovation are going to have their desired effect of bringing
therapeutic solutions to market faster. 3
The FDA and medical innovation
In recent years, technological innovations in medical sciences have led to rapid advancements in digital health, targeted medicines, regenerative medicines such as cell and gene therapies, and other breakthrough therapeutics. The FDA has always tried to stay at the forefront of medical innovation and to support novel solutions without compromising efficacy and safety. Following the signing into law of the 21st Century Cures Act by President Barack Obama in December 2016, the FDA has implemented several changes to reflect its commitment to better regulation and advancement of public health, particularly in support of innovative therapies for which there were previously no regulatory guidelines. 4 Among other things, the Act aims to speed up the FDA’s approval process for new drugs and medical devices, as well as facilitate development and approval of targeted drugs for the treatment of rare diseases. 5 In response, the FDA has implemented several innovative initiatives aimed at increasing the efficiency of clinical trials, improving the efficiency and speed of its drug review process, harnessing real-world evidence, and curating standards for new medical technologies. 4 These initiatives have been designed to support innovations in drug development and establish new standards to guide the FDA’s regulations around innovative medicines.
Transforming drug review processes
Beginning in 2017, the FDA, particularly the CDER, began the modernization of its internal organizational structure to simplify its drug review process by breaking down review silos between different scientific disciplines. The goal is for FDA review teams to be centralized around particular disease types, integrated across the disciplines involved in drug review, and thus better able to implement a more structured approach to data review in the evaluation and analysis of output from agile clinical trials. Under the new structure, all drugs, biologics and devices related to a particular disease type will be reviewed by the same team. Being disease-focused rather than product-focused gives the subject matter experts better resources to improve the clinical and regulatory principles the FDA uses to evaluate the safety and efficacy of innovative products. When reviewing innovative products, the new structure and processes make possible deeper insights into the risks, extensive assessment of benefits, and incorporation of patients’ opinions. Thus, it supports the FDA’s continued efforts to base regulatory decisions – including decisions around medical innovations – on well-informed analyses of benefit-risk balance. 6 By concentrating expertise around disease types, the FDA is also better able to engage with stakeholders on new technologies through their Emerging Technology Program – a program designed to support the industry’s implementation of innovative approaches to the design and manufacturing of medical products. 7
Innovative clinical trials and real-world evidence
The FDA is supporting innovations in clinical trials by encouraging the use of novel tools such as modeling and simulation. These tools can be applied in several ways to significantly speed up product development. Among other functions, they can be used to forecast clinical outcomes, explore alternative trial designs, assess possible adverse events, and support product effectiveness. 4 As an example, at least 90% of FDA drug approvals in 2018 were supported by software and services from Certara, a company that offers a platform for simulation and modeling, regulatory science, and scientific value assessment. 8 By innovating towards faster drug trials, while still maintaining its gold standard for safety and efficacy, the FDA aims to make novel and innovative medicines get to the patients that need them faster than ever before. In addition, the FDA is collaborating with the Clinical Trials Transformation Initiative clinical trials more efficient. One example is the seamless trial design, which involves combining the usual three phases of drug trials into one seamless trial (called expansion cohort trial), thus eliminating the time and cost spent waiting between trial phases. Another example is the use of master protocols that study multiple therapies, multiple diseases, or both, such as basket trials, umbrella trials and platform trials. Such designs can significantly lower the cost and time needed to conduct drug trials while still being rigorous enough to detect efficacy and safety signals earlier in the development process. 6 These trial designs also answer some important clinical questions that would go unanswered in standard trials and they characteristically use a common infrastructure, thus streamlining trial logistics, improving data quality, and facilitating data collection and sharing. 9
Encouraging and expediating innovation
The former FDA commissioner, Dr Scott Gottlieb, had stated that the FDA’s longstanding goal for medical care is to ensure that the right drug or device is delivered to the right patient at the right time. In fulfilling this goal, the FDA is committed not only to ensuring the safety and efficacy of medical products, but also to encouraging and expediting medical innovations.
1 FDA regulator: Medical innovation won’t work without major changes to healthcare (September 2019). Retrieved from: https://www.beckershospitalreview.com/innovation/fda-regulator-medical-innovation-won-t-work-without-major-changes-to-healthcare.html
2 ‘It’s not working’: An FDA insider’s view of where medical innovation falls short (September 2019). Retrieved from: https://www.latimes.com/science/story/2019-09-07/fda-medical-innovation-falls-short
3 CDER chief Janet Woodcock has a message for pharma: It’s not working, and it won’t work in the future (September 2019). Retrieved from: https://endpts.com/cder-chief-janet-woodcock-has-a-message-for-pharma-its-not-working-and-it-wont-work-in-the-future/
4 Implementing The 21st Century Cures Act: A 2018 Update From FDA And NIH (July 2018). Retrieved from: https://www.fda.gov/newsevents/ congressional-testimony/implementing-21st- century-cures-act-2018-update-fda-and-nih-07242018
5 21st Century Cures Act (April 2017). Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424829/
6 FDA’s Comprehensive Effort to Advance New Innovations: Initiatives to Modernize for Innovation (August 2018). Retrieved from: https://www.fda.gov/news-events/fda-voices-perspectives-fda- leadership-and-experts/fdas-comprehensive-effort-advance-new-innovationsinitiatives- modernize-innovation 10/29/2019 The FDA’S take on Medical Innovation https://www.thepharmaletter.com/article/the-fda-s-take-on-medical-innovation 3/3
7 Emerging Technology Program (October 2019). Retrieved from: https://www.fda.gov/about- fda/center-drug-evaluation-and-researchcder/ emerging-technology-program
8 Certara Supported 90+ Percent of US FDA Novel New Drug Approvals for Fourth Consecutive Year (January 2019). Retrieved from: https://www.certara.com/pressreleases/certara-supported-90- percent-of-us-fda-novel-new-drug-approvals-for-fourth-consecutive-year
9 Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both (July 2017). Retrieved from: https://www.nejm.org/doi/full/10.1056/NEJMra1510062
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