The OpenTrialsFDA team, which is in the running for the Open Science Prize thanks to funding of the Wellcome Trust, the US National Institutes of Health (NIH) and the Howard Hughes Medical Institute, will present the prototype of the new OpenTrialsFDA interface at the BD2K Open Data Science Symposium on 1 December 2016. Following the event, the public is asked to help select the most promising, innovative and impactful prototypes from among the six Open Science Prize finalists – one of which will receive the grand prize of $230,000. In this blog you can find out more about OpenTrialsFDA through the Frequently Asked Questions we’ve collected: a summary of the work is available here.
General questions
Background
The OpenTrialsFDA team is one of the six finalists for the Open Science Prize: a global science competition to make both the outputs from science and the research process broadly accessible to the public. This is a collaboration between Dr. Erick Turner, Dr. Ben Goldacre and the OpenTrials team at Open Knowledge International. Competing for the $230,000 prize that will be awarded to the winner in February 2017, OpenTrialsFDA is working on a prototype that will make the information hidden in the user-unfriendly drug approval packages of the FDA (the US Food and Drug Administration) more easily accessible and searchable, and link these to documents and data related to clinical trials.
The work is closely related to the OpenTrials project, which aims to locate, match, and share all publicly accessible data and documents, on all trials conducted, on all medicines and other treatments, globally. OpenTrials is aggregating this information from a wide variety of existing sources and aims to provide a comprehensive picture of the data and documents on clinical trials conducted on medicines and other treatments around the world.
What is the scope of OpenTrialsFDA?
OpenTrialsFDA works on making clinical trial data from the FDA (the US Food and Drug Administration) more easily accessible and searchable. Until now, this information has been hidden in the user-unfriendly Drug Approval Packages that the FDA publishes via its dataportal [email protected]. These documents are notoriously difficult to access, aggregate, and search, since the [email protected] website itself is not intuitive to navigate, and the reviews are stored as individual PDFs which, except for relatively new drugs, cannot be searched. OpenTrialsFDA will extract the relevant data from the FDA documents, link it to other clinical trial data and present it through a new user-friendly web interface. Any user will be able to type in a drug name, and see all the places where this drug is mentioned in an FDA document. Users will also be able to access, search and present this information through the application programming interfaces (APIs) the team will produce.
Who is behind OpenTrialsFDA?
OpenTrialsFDA is a collaboration between Dr. Erick Turner (a psychiatrist-researcher and transparency advocate), Dr. Ben Goldacre (Senior Clinical Research Fellow in the Centre for Evidence Based Medicine at the University of Oxford) and the team behind OpenTrials at Open Knowledge International.
[email protected] is a searchable catalog of the US Food and Drug Administration (FDA) approved drug products, both prescription and over the counter, with links to documents relating to marketing approval. More information is available from their FAQ section.
What are FDA drug approval packages?
FDA Drug Approval Packages consist of FDA employees’ reviews of new drug applications (NDAs) submitted by pharmaceutical companies seeking approval to market their drugs in the US. These NDAs consist primarily of clinical study reports (CSRs). Some drugs have more than one approval package, because approval is granted not for a drug per se, but for each drug-indication combination.
How will OpenTrialsFDA improve access to the FDA data?
The team will scrape the FDA website and extract the relevant information from the PDFs through a process of OCR (optical character recognition). Through the new OpenTrialsFDA interface, users will be able to explore and discover the FDA data. In addition, the information will be integrated into the OpenTrials database, so that the FDA report can be linked to reports from other sources, such as ClinicalTrials.gov, EU CTR, HRA, WHO ICTRP, and PubMed.
How does the FDA review process differ from the peer review process used for manuscripts submitted to journals?
The key is the before-versus-after-the-trial aspect. Before the sponsor can begin a trial in the US, it must submit the trial protocol to the FDA. By means of this “pre-trial” review of the protocol, the FDA learns (1) that that trial is to be conducted and (2) the nitty-gritty methodological details. That way, a few years later, when the sponsor submits its NDA, the reviewer compares the clinical study report (CSR) to the original protocol to determine (1) whether any studies have been omitted and (2) whether any outcomes have been switched. By contrast, in the world of peer-reviewed journal articles, there is no “pre-trial” review, allowing both (1) and (2) to take place.
Who authors FDA reviews?
The FDA review team is multidisciplinary, yielding different types of reviews. Medical reviews are usually authored by physicians who summarize and evaluates the data on drug efficacy and safety. Statistical reviews are carried out by statisticians who test whether they can replicate the sponsor’s results using the patient-level data submitted electronically. There are other review disciplines, e.g. chemistry, pharmacology-toxicology, whose reviews pertain primarily to the preclinical phase and early clinical (human) phases of drug development.
What is the Open Science Prize?
The Open Science Prize is a collaboration between the Wellcome Trust, the US National Institutes of Health (NIH) and the Howard Hughes Medical Institute. Its goal is to unleash the power of open content and data to advance biomedical research and its application for health benefit. The OpenTrialsFDA team is one of the six finalist teams that were selected in May 2016. All teams will showcase their prototypes at the BD2K Open Data Science Symposium on 1 December 2016, when public voting will begin. The public is asked to help select the most promising, innovative and impactful prototypes from among the six finalists – among which one will receive the grand prize of $230,000.
Troubleshooting
In case you’re having difficulty finding the right information in the [email protected] portal, here are some troubleshooting questions to help you:
Was the drug approved before or after 1997?
The FDA started posting reviews (Drug Approval Packages) in 1997. If the drug in question was approved in 1996 or earlier, you probably will not find it posted.
Are you sure that the use you’re interested in is not off-label, ie. that the FDA approved it for the indication you’re interested in?
Oftentimes drugs are used widely for a certain condition (indication) for which the FDA has not granted approval (off-label use). If you check the product label (e.g. at https://dailymed.nlm.nih.gov/dailymed/index.cfm) and look within the section on “Indications and Usage”, you will see a list of the approved indications.
Are you looking for indication #1 or one of the subsequent indications?
A given drug might be FDA-approved for multiple indications. The FDA is careful about posting the Drug Approval Package for the first indication (the one that allowed that drug to enter the market), but for subsequent indications (#2, #3, etc.), it’s more hit-or-miss.
If you are motivated, one way to get such reviews is to file a Freedom of Information request here; but be warned—the FDA might take months or longer to fulfill your request. If you do get such reviews, we would appreciate your sharing it with us so we can add to OpenTrialsFDA and make it readily available to others.
Did you use the generic name or brand name?
If you use the generic name, you will probably get lots of hits: one for when the molecule was first being introduced to the market plus hits for subsequent generic versions. The FDA does its review for efficacy and safety when the molecule is first introduced to the market. Years later, when the patent expires, generic equivalents get approved, but what the FDA cares about at this stage is bioequivalence (in terms of blood levels) to the original brand name version. Thus generics do not have to demonstrate efficacy and safety all over again, which is why these approval packages generally contain little or no such data.
Is the review an NDA or an ANDA?
Please see the question and answer immediately above. NDAs (new drug applications) correspond to brand name versions, while ANDAs (abbreviated new drug applications) correspond to generic equivalents. They are abbreviated because less is required of the sponsor (see above). Assuming you are interested in drug efficacy and/or safety (and not bioequivalence), you will want to focus on NDAs and ignore ANDAs.
Is this the original or a subsequent formulation of a drug?
This is similar to the issue brand name versions vs. generic versions (see above). The burden of proof regarding efficacy and safety is highest when a molecule is first entering the market. A given drug will often enter the market as an immediate release (IR) formulation, before which the FDA will do its most comprehensive review of drug efficacy and safety. Some years later, the sponsor may seek approval for a sustained-release (SR) formulation, but by that time, millions of patients have already been exposed to the IR formulation. Because it is relatively unlikely that the efficacy and/or safety profile will differ a great deal between the IR and the SR, the SR may have to do fewer clinical trials compared to its IR version.
Want to get involved? Have further questions?
Please email us at [email protected]. This email is sent to Emma Beer, the Project Manager for OpenTrials and Ben Goldacre, its Principal Investigator.
For further project updates, check the OpenTrialsFDA page at https://fda.opentrials.net or follow us on Twitter: @opentrials
The launch will take place at the ‘
