“Fostering Transparency to Improve Public Health”
Scott Gottlieb, MD
Commissioner of Food and Drugs
Johns Hopkins Bloomberg School of Public Health
Jan. 16, 2018
Transparency can be a powerful tool for innovation.
New platforms for analyzing and visualizing large, complex datasets present important new opportunities for the research and development community, for regulators, and for clinicians. It allows people to harness data to advance the safe and efficient development of new therapies to address unmet medical needs; to tailor clinical care to individual patient characteristics and preferences; and to communicate information supporting regulatory decision-making in ways that engender greater public confidence in those decisions.
The FDA’s goal is to advance transparency without reducing incentives to innovate. This can be accomplished by meeting our statutory responsibility for protecting confidential commercial information, trade secrets, and personally identifiable data, while disseminating more information that supports and informs regulatory decisions – and patient care -- once products are approved for use.
With these safeguards in place, transparency is a tide that can lift all boats. It can enable stakeholders to better address common challenges in the product development process, to identify areas requiring additional post-market research, and to generate the data necessary to meet the FDA’s gold standard for assuring produce safety and efficacy.
The FDA’s modern transparency strategy began with Dr. Josh Sharfstein’s leadership of the FDA’s Transparency Taskforce and subsequent recommendations in 2010. And we continue to expand the agency’s commitment to transparency today.
Since 2010, we’ve been implementing some new tools that allow the public and regulated industry to monitor and evaluate our performance. This includes the efforts we make through FDA’s Data Dashboard. The Dashboard includes publicly available datasets and a variety of data visualization tools that enable a better understanding of agency compliance actions, inspections, recalls, and imports, updated on a quarterly or monthly basis. We also maintain monthly updated dashboards tracking our progress implementing key statutes.
By opening more of our internal, high quality datasets to the public, data scientists, medical researchers, and programmers -- people are finding new ways to transform raw data into more useable information for patients, consumers, and clinicians – especially through applications that are accessible through smartphones, laptops, and tablets. For instance, the FDA’s openFDA project provides application programming interfaces or APIs and full sets of downloadable FDA data files for numerous high priority, scalable structured datasets, including for adverse events, drug product labeling, and recall enforcement reports.
To date, openFDA includes nearly eight million drug adverse event reports; 7,600 drug enforcement reports; and 116,000 drug label files. In the last 30 days alone, the drug adverse event file was accessed more than 2.4 million times. The interface supports an open source user community, including the sharing of source code for prototype projects and techniques for their use through GitHub, Twitter, and StackExchange. There have been 75 million API calls for these datasets.
Also in 2016 FDA made public, for the first time, data it receives about adverse events related to foods, dietary supplements and cosmetics. The CFSAN Adverse Event Reporting System (CAERS) data can provide signals of potential hazards and are available through openFDA.
Rapid communication of important public health enforcement actions is another hallmark of our commitment to transparency. Beginning last summer, FDA’s Office of Regulatory Affairs (ORA) -- Office of Enforcement and Import Operations (OEIO) -- began including information about products that met the definition of a recall, according to the code of federal regulations, but had not yet been classified by the level of hazard, in our weekly enforcement reports.
Today, the search functionality on FDA’s website has been updated so that the public and media can search our enforcement reports for these recalls that are labeled “not yet classified.” This allows a better-informed public to respond to product recalls weeks or even months faster than waiting for FDA to conclude a full recall classification.
We’ve made much progress. But stakeholders continue to request greater transparency in the drug approval process, and greater access to useable information on those approvals. I believe they’re right. We need to look for ways to be more forthcoming with the information we have; within the boundaries of our statute and regulatory obligations.
Much of our information concerns products that are integral to people’s families – the foods they eat, the pets they love, and the medicines they use. People deserve to have as much information about these products as we can reliably provide. And there are more tools available than ever before to help consumers filter this information and to help third parties harness it into more usable knowledge. We have a public health obligation to keep people fully informed of the safety and benefits of the products they use to improve their lives.
We’re taking some new steps to meet these commitments.
Today, I’m announcing two important initiatives that I hope will provide greater transparency and efficiency in the agency’s review of New Drug Applications and Biological License Applications. Together, these initiatives will give patients and researchers new insight into the data and decision-making process behind the FDA’s approval of new drugs. These new changes will also enhance the ability of patients and researchers to track individual product development from initial enrollment of subjects in clinical trials posted on the ClinicalTrials.gov website through every public FDA communication and decision regarding that product based on a unique, new numerical identifier.
First, beginning this month, our center for drugs or CDER, is launching a pilot to evaluate whether disclosing certain summaries of clinical information – called Clinical Study Reports or CSRs – following the approval of a New Drug Application (NDA), can improve the public’s access to drug approval information. To start, the pilot will include up to nine drug applications whose sponsors volunteer to participate.
The pilot will test a process – to be run by FDA’s drug center -- for selecting, redacting, and posting CSR information on the public website Drugs@FDA.gov that the FDA uses to provide data on approved drugs.
Applications to be included in the pilot will be selected based on criteria including their novelty, scientific interest, and whether the drug is a new molecular entity.
A CSR is a portion of the drug file, related to a clinical trial, that contains a detailed summary of the bottom line information on the methods and results of a trial. A CSR is a scientific document addressing efficacy and safety. We expect that making some CSRs publicly available after approval will provide stakeholders with more information on an application’s clinical evidence and FDA’s decision-making process. It can help those interested in that detailed data – for example, academic researchers who want to study a specific drug and need access to summaries of the bottom line data to better inform their research.
This will be the first time that FDA is proactively disclosing clinical summary reports from sponsors to the public. The CSR sections disclosed as part of the pilot will include the study report body, the study protocol and amendments, and the statistical analysis plan for each of the participating product’s pivotal studies. Clinical summary reports will be posted on a new FDA web page describing the pilot program, in addition to appearing on drugs@FDA with the drug’s approval information, soon after the product is approved.
One of the goals of the pilot is to enhance access to clinical information by medical researchers, the drug development community, and the public. While FDA does provide access to drug application action packages that include all discipline reviews after a drug has been approved, their utility is limited by their complexity.
While these summaries provide a window into the basis for our approval decisions, they are packaged in a format that can – at times -- make it difficult for external audiences to decipher the key clinical evidence that supported the agency’s approval decisions.
We believe that by posting key portions of CSRs publicly, we’ll both comply with our existing obligations to make certain summary materials publicly available upon approval, and make that material significantly more practical and user-friendly for key collaborators – for example, for medical researchers who want to further study a specific drug beyond the clinical evidence that supported its approval.
Once the clinical summary report pilot program is concluded, we’ll seek public feedback through a Federal Register notice and docket for public comments. We look forward to learning more about how to best support stakeholders’ needs.
At the same time, we’re taking another new step to make it easier for patients and clinicians to track new therapies as they advance through product development and regulatory checkpoints. Right now, the majority of publicly and privately supported clinical trials around the world register on the National Institutes of Health’s database, ClinicalTrials.gov. This website provides easy access to information on studies in a wide range of diseases and conditions.
Ultimately, some of these clinical trials involving new drugs form the basis of an application seeking FDA approval. These trial results are often of great interest to patient and research communities. Yet tracking a specific trial from its active state on ClinicalTrials.gov to FDA’s many activities – from advisory committee discussions to approval and inclusion a product label, for example, can be incredibly challenging.
In response, we plan to increase transparency around clinical research posted on ClinicalTrials.gov by adding the special identifier number that all clinical trials registered through ClinicalTrials.gov will use to link to FDA communications about specific drugs, including product labeling and even our advisory committee meeting materials.
This new number will be called the NCT number.
Members of the patient, academic, and scientific communities can then use this number to follow and track clinical research from a drug’s development throughout the regulatory process.
This number will make it easier to correlate the clinical trial listings on ClinicalTrials.gov to FDA communications about specific drugs, including product labeling and even our advisory committee meeting materials.
Including this number on FDA materials could greatly benefit all those interested in following the progress of specific clinical research.
We’re also continuing to explore whether it would be possible – under existing statutory authority or through a change in the governing law – to release additional information from complete response letters (CRLs) related to clinical safety and efficacy that could have significant public health value. Releasing all the CRLs would be administratively burdensome, given the likelihood we would continue to redact certain proprietary information from these letters. And not all the letters have information that would directly inform clinical practice. For example, many letters primarily relate to manufacturing shortcomings with new drug applications that are eventually resolved.
But some of the letters do contain information that could be directly relevant to patients. We're evaluating whether there is a subset of the complete response letters where there are especially important public health reasons to redact and release these letters. For example, letters that have safety-related findings or recommendations that could help inform patients and providers about the profile of already-marketed products. Releasing this information could enhance patient safety, by reducing the number of potentially futile trials, and spare patients exposure to potential risks without the prospect of a likely benefit. It can also help better inform clinical practice.
We’re committed to enhancing transparency throughout the work we do at the FDA. This is especially true when these efforts have the potential to foster further research and discovery across the scientific community and clinical care. And we’ll continue to seek additional opportunities to foster greater access to key scientific information, and clarity around regulatory decision making, wherever appropriate.
The powerful synergy between high quality public health datasets and therapeutic innovation has been evident for more than 50 years - long before the advent of the desktop computer, let alone machine learning and genomics. Arguably two of the most important and impactful public health initiatives undertaken in the post-war era were the launch of the Framingham Heart Study in 1948, and the Surgeon General’s landmark report on smoking in 1964.
The Surgeon General’s report was deeply informed by epidemiologic evidence from the Framingham study, along with a similar cohort from Albany, New York. Over the ensuing decades, subsequent analysis of the original Framingham cohort, and new generations of participants, spouses, and children helped revolutionize our understanding of risk factors for cardiovascular disease – including smoking, obesity, and high cholesterol. It led to the development of the Framingham Risk Score.
That risk score validated pharmacologic and behavioral interventions that reduced the risk of serious and fatal complications from heart disease; from the wider use of statin drugs to smoking cessation.
The combination of better science and a better-informed public led to a dramatic decline in mortality from all forms of cardiovascular disease, including coronary heart disease, stroke, and coronary artery disease.
The National Heart, Lung, and Blood Institute of the National Institutes of Health; reports that the death rate from cardiovascular disease peaked just before the Surgeon General’s 1964 report on smoking, and started falling by the late 1960s. From 1968 to 2010, the age-adjusted death rate from cardiovascular disease has declined by nearly 70%.1
Today, the Framingham study has expanded to include a biospecimen bank and the collection of both phenotypic and genomic data, and any researcher can request access to the underlying datasets.
Technology, no matter how powerful, is always just a tool. It’s our commitment to the transparent, responsible, and science-based use of those tools that gives them their potential to save and improve lives – and to build many more practical “Framingham” studies for the 21st Century based on a growing number of open source tools and datasets.
To reach their full potential, open data, real world data, wearable and implantable diagnostics, and advanced trial designs, will all have to validated through transparent processes that gain the trust and confidence of all stakeholders in their reliability.
The FDA will be at the epicenter of this process.
Not by inventing new values; but by continually recommitting ourselves to the agency’s century-long commitment to its scientific gold standard for evaluating product safety and effectiveness, and by remaining a benchmark for global regulatory excellence.