The agency tasked with regulating drug approvals can provide researchers with the best source of data on other new products.
By David Pittman
The Food and Drug Administration (FDA)—while also the gatekeeper of what drugs do and don’t make it into drugstores and exam rooms—is a treasure trove of information for data-craving researchers looking for every little morsel of insight on drugs they hope will one day win FDA’s blessing.
FDA makes labeling information and review documents available on its website, which contain valuable information on drug characteristics such as drug-drug interactions, dosing, and other critical clinical characteristics. Pharmaceutical manufacturers submit to the agency mounds of data it collects during clinical trials and post-market review, and FDA publishes most of that in the name of transparency, public safety, and collective learning.
Drug researchers can improve their work if they learn how to tap into this body of information, a trio of speakers explained during an October 24, 2019, American Association of Pharmaceutical Scientists webinar, entitled Navigating and Understanding FDA Review Documents.
The Drugs@FDA webpage is the searchable database of FDA-approved drug products, over-the-counter human drugs, and biological therapeutic products. It offers drug labels, approval letters, reviews, and other information for the majority of drug products approved since 1998, said Kunyi Wu, Pharm.D., a clinical pharmacologist in the Office of Clinical Pharmacology at FDA’s Center for Drug Evaluation and Research.
The database is updated daily, so it provides the latest information publicly available. FDA labels offer, among other details, clinical pharmacology characteristics, including pharmacodynamics and pharmacokinetics (PK).
The Drugs@FDA webpage also lists the documents FDA reviewers compile for drug applications sorted by different disciplines including chemistry and clinical pharmacology. It’s here where researchers can find answers to problems they may be investigating.
As an example, Wu demonstrated how review documents could be searched to find why Baxdela (delafloxacin), an antibiotic used to treat acute bacterial skin infections, has recommendations for dosing adjustments for IV infusions but not oral tablets in patients with severe renal impairment. Looking at the clinical pharmacology review sections, one can see the rationale for the FDA-approved dosing levels for different formulations, which is basically PK studies showing patients reacting differently to the drug in different formulations.
Wu pointed out that FDA will gray-out or redact proprietary or non-public information on drugs, which can include methods for PK analysis and patient-identifying data. Also, the Drugs@FDA webpage will not list supplemental reviews, which would be used for new formulations or patient populations like in pediatrics. Instead, required post-marketing pediatric studies are posted on a separate FDA page.
J.Russell May, Pharm.D., FASHP, a clinical professor and associate department head in the Department of Clinical and Administrative Pharmacy at the University of Georgia College of Pharmacy, outlined several other scenarios where FDA labeling may be useful for those in pharmaceutical sciences.
Nourianz (istradefylline) was recently approved as an adjuvant treatment for Parkinson Disease patients experiencing “off” episodes. It is a known weak inhibitor of the substrate CYP 3A4. But what if a patient also takes the cholesterol drug lomitapide, which is metabolized by CYP 3A4?
"We get lots of questions on drug-drug interactions,” May said. “Many times, they’re relatively easy to answer…But with new drugs, that’s sometimes difficult.”
The drug’s FDA-approved label lists a table of substrate inhibitors and inducers, and one can reference just how weak of an inhibitor istradefylline is and determine how much to increase the dose of lomitapide. Because this information is updated as it comes in and is approved, it provides the most up-to-date resource.
“Now you have the information and you can discuss risk versus benefit,” May said. “That’s where the discussion comes in.”
Drug trial snapshots provided by FDA offer detailed information on the patient demographics of clinical trials. This is helpful to know if it is appropriate to apply evidence since the studied population may be different from your clinical patients, May said. Such data may be otherwise unpublished or on file with the manufacturer.
FDA approval letters will list detailed post-marketing study requirements, including what studies must be done on what populations by specific times. This is useful information, May said, because researchers can look at interim and final reports or participate with manufacturers on post-marketing studies.
Pharmacogenomics is an emerging field that can also be better supported by using the FDA website. The agency lists known genetic factors that may be important for the prescribing of a particular medication.
“For some drug classes, the response rates are ranging from 50 to 75 percent. Well, why is a medication effective in one patient and not in another patient?” May asked. “It may be due to some genetic differences.”
Researchers shouldn’t overlook supplementing what they learn from these FDA documents with other, outside data, explained Brian Furmanski, Ph.D., a clinical pharmacologist at Nuventra, a consulting firm to help drug companies go through the approval process. For example, the European Medicines Agency and Health Canada provide summaries of the safety and efficacy information that is used to make regulatory decisions. “Although those are fairly similar in content to the FDA,” Furmanski said.
“There’s been this movement of data transparency,” he added. “It’s an effort to provide transparency in the drug development process from an industry along with global health regulators. They’re beginning to share clinical study reports as well as patient level data.”
ClinicalTrails.gov, ran by the National Institutes of Health, shares ongoing and past clinical studies from all over the world. Federal law requires studies’ results used to support FDA decisions be submitted within a year of completion, although observational, phase 1, and behavioral health studies are exempt from posting.
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David Pittman is a science and medical writer based in Washington, D.C.