With the swearing in of Dr. Scott Gottlieb as Commissioner of Food and Drugs in May, many have wondered as to the climate he will set for the US FDA. Certara’s mission and business thesis aligns with the FDA’s July 7 announcement regarding the steps it is taking to implement the 21st Century Cures Act. In this announcement, Dr. Gottlieb cited three areas of focus for the agency in the next several years.
1. Leveraging modeling and simulation (M&S) to increase the efficiency of drug development: Quoting Dr. Gottlieb on his view of the role of M&S in drug development:
Modeling and simulation play a critical role in organizing diverse data sets and exploring alternate study designs. This enables safe and effective new therapeutics to advance more efficiently through the different stages of clinical trials. FDA’s efforts in modeling and simulation are enabled through multiple collaborations with external parties that provide additional expertise and infrastructure to advance the development of these state-of-the-art technologies. FDA’s Center for Drug Evaluation and Research (CDER) is currently using modeling and simulation to predict clinical outcomes, inform clinical trial designs, support evidence of effectiveness, optimize dosing, predict product safety, and evaluate potential adverse event mechanisms.
He also wrote about using of M&S to support precision dosing—providing the right drug dose to maximize therapeutic benefit while reducing risk for each individual patient. The emerging precision dosing field harnesses the explosion of genomic data and various markers of bodily functions using mathematical modeling to ensure that individuals get the best possible treatment.
In addition, he cited CDER’s use of M&S to review Investigational New Drugs Applications (INDs) and New Drug Applications (NDAs). M&S can inform clinical management strategies described in drug labels. In particular, physiologically based pharmacokinetic (PBPK) models can provide insight into drug mechanisms. This approach considers both intrinsic and extrinsic factors. These factors include genotype, disease state, renal/hepatic impairment, ethnicity and age. PBPK models incorporate information about how drug exposure changes with drug-induced enzymatic inhibition. Thus, the models can predict and quantify the magnitude of potential drug-drug interactions (DDIs). Sometimes, they can even eliminate the need for additional clinical studies. This tool can be used to develop dosing recommendations for special populations—children, pregnant women, and patients with organ impairment—who can be difficult or impossible to be studied via clinical trials.
2. Using natural history databases to support model-based drug development: To make clinical trials more efficient, the agency is looking to model some aspects of the placebo arm of clinical drug trials. This will be especially impactful for rare diseases—defined as diseases affecting less than 1 in 2000 people. Because of small numbers of patients, it is extremely difficult to recruit enough volunteers for inclusion in clinical trials investigating orphan drugs. The FDA is looking to create natural history databases to support these efforts.
Publicly available clinical trial data represent an underutilized source of information. If properly extracted and analyzed, they provide valuable information to support drug development decisions. Based on years of experience exploring and analyzing publicly available data to perform model-based meta-analysis (MBMA) for our clients, we created an extensive collection of analysis-ready Clinical Trial Outcomes Databases. These databases capture high-quality public source data on drug efficacy and safety, drug, trial, and disease characteristics, trial design, and other relevant information to make key development and commercial decisions.
Our 40 databases provide comprehensive up-to-date information on major therapeutic areas such as CNS & Pain, Oncology, Immunology, Metabolic, Infectious Diseases, and more. For easy access, our Collaborate portal can be used to explore the databases through the integrated Clinical Outcomes Database Explorer (CODEx) interface. CODEx enables users to quickly visualize, explore, analyze, and communicate database content using a variety of highly interactive tools.
3. A mandate for patient-centric drug development: The agency also plans to focus on patient-centric drug development. As stated in the Plan for Issuance of Patient‐Focused Drug Development Guidance:
Patients who live with a disease have a direct stake in drug development and in the outcome of the FDA review process for new drugs. Patients are also in a unique position to contribute to an understanding of benefit and risk considerations throughout the medical product development process. Under the 2012 FDASIA reauthorization of the Prescription Drug User Fee Act (PDUFA), FDA pioneered the use of patient focused drug development (PFDD) meetings to help address the need for systematic collection of direct patient input. The twenty-two PFDD meetings we have held so far have each focused on a different disease area and have identified key findings including that patients living with a disease are experts on what it is like to live with the condition. In addition, the meeting highlighted that what patients care most about may not always be factored into clinical trials or approved labeling.
I’m happy to see the growth in patient-centric drug development because ultimately we are working to bring them safer, more effective medications to improve their quality of life. We have an ethical imperative to consider the patient’s perspective in designing clinical studies. Starting with the study design, are we performing only the necessary assessments? Are we using technology like modeling and simulation to minimize blood draws? Are we using patient-friendly language so that clinical trial participants can understand the summary of their study results (the plain language summary)? Synchrogenix, a Certara company, and the nonprofit Center for Information and Study of Clinical Research Participation (CISCRP)—an organization dedicated to educating and informing the public and patients about clinical research—have an exclusive partnership to provide lay language clinical trial results to clinical trial volunteers. Through this collaboration, Synchrogenix, Certara’s regulatory writing consultancy, significantly increased global medical writing capabilities supporting an initiative that CISCRP pioneered four years ago. This new partnership combines Synchrogenix’s technology-enabled operational expertise and clinical writing talents with CISCRP’s unbiased governance and dedication to engaging patients and the public in the spirit originally intended of the clinical research process.
While none of us can be certain what the future will bring, I am encouraged by the tone that the new commissioner is setting at the agency. He has endorsed the technology needed to advance the science of drug development while keeping patient’s needs at the forefront. The FDA of the 21st century is developing a regulatory climate that helps sponsors expedite getting crucial medicines to the patients who need them most.