FDA Advisory Committee Meetings

The U.S. Food and Drug Administration, to assist in its mission to protect and promote the public health, uses 50 committees and panels to obtain independent expert advice on scientific, technical, and policy matters. This page features select Advisory Committee meetings where Sentinel data have been presented or discussed.

 

Sentinel Data in Action: Accounts from FDA
 

   

Sentinel Data on use of Higher Dosage Strength Opioid Analgesics Featured at Recent FDA Advisory Committee

Corinne Woods, RPh, MPH; Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD
June 11-12, 2019

 

In June 2019, FDA held a joint meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee to discuss the clinical utility of and safety concerns associated with the higher range of opioid analgesic dosing (both in terms of higher strength products and higher daily doses) in the outpatient setting.  FDA was interested in better understanding current clinical use and situations that may warrant use of higher doses of opioid analgesics. FDA was also interested in discussing the magnitude and frequency of harms associated with higher doses of opioid analgesics relative to lower doses, as well as optimal strategies for managing these risks while ensuring access to appropriate pain management for patients. At the Advisory Committee meeting, FDA presented utilization data, including analyses of Sentinel data.

FDA analyzed results from 17 Sentinel Data Partners to help the committee understand the utilization of higher dosage strength opioid analgesic products when compared to lower dosage strength opioid analgesic products and transdermal opioid analgesics. FDA evaluated utilization patterns, patients’ cumulative durations of therapy for the opioid analgesic categories, comorbidities, and the presence of claims with diagnoses of interest, such as pain-related diagnosis codes, mental illness, or substance use disorder. The results showed that the use of higher dosage strength opioid analgesic products comprised a small portion of all opioid analgesic use and has declined in recent years. Compared to patients on lower dosage strength opioid analgesic products, patients on higher dose opioid analgesic products had longer therapy with any of the higher dosage strength products. They also appeared to have higher prevalence of comorbidities, mental health conditions, or substance abuse. Patients on higher dose opioid analgesic products appeared clinically similar to patients on transdermal opioid analgesic therapy.

A verbatim transcript is available approximately 10-12 weeks following the meeting date, in most instances.

Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee

 

    

Sentinel Data on the Risk of Diabetic Ketoacidosis with Off-Label Use of SGLT2 Inhibitors Featured at Recent FDA Advisory Committee

Christian Hampp PhD; Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD
January 17, 2019

 

In January 2019, the FDA held a meeting of the Endocrinologic and Metabolic Drugs Advisory Committee to discuss the benefits and risks of sotagliflozin, as the first sodium-glucose-contransporter-2 inhibitor (SGLT2 inhibitor) seeking indication for the treatment of adults with type-1 diabetes mellitus (T1DM), as an adjunct to insulin. Clinical trials in type-1 diabetic patients showed an increased risk of diabetic ketoacidosis (DKA) with sotagliflozin, compared with placebo, amid a background of insulin therapy. Other SGLT2 inhibitors are currently approved for the treatment of adults with T2DM. 

We analyzed data from 17 Sentinel Data Partners to help the committee understand the frequency of off-label utilization of SGLT2 inhibitors for T1DM and associated real-world rates of DKA. We also conducted a formal age- and sex standardized comparison of observed DKA event counts in Sentinel with counts that would be expected if the sotagliflozin clinical trials incidence rates were present in the Sentinel population. With these analyses, we showed that SGLT2 inhibitors are used off-label in the treatment for T1DM, albeit at low overall rates but at higher rates among younger patients. Rates for DKA during off-label use of SGLT2 inhibitors were high, especially among younger patients, and especially among younger women. Real-world rates for DKA in Sentinel were higher than expected based on clinical trials.

The committee followed the Sentinel data presentation and posed several questions, including about drug utilization by age. In the discussion of sotagliflozin's benefits and risks, members of the committee expressed concern that DKA rates in the real world could be higher than in the clinical trial setting, which is what the Sentinel data suggested. The committee was split 8-8 on the question as to whether sotagliflozin's benefits outweigh the risks when used for T1DM.

Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee: SGLT-2 Inhibitors and Diabetic Ketoacidosis

 

    

Sentinel Data Contextualizes Results from a Post-Market Cardiovascular Risk Trial

Marie Bradley PhD, MPharm, MSc.PH; Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD
January 11, 2019

 

Febuxostat (Uloric) is a urate lowering therapy (ULT) used in the management of hyperuricemia in gout that was FDA approved in 2009. It is the only alternative xanthine oxidase inhibitor (XOI) for patients who cannot take allopurinol due to hypersensitivity reactions, or the presence of chronic kidney disease. FDA’s Arthritis Advisory Committee (AAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) met on January 11, 2019 to discuss the results from the post-marketing safety trial “Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities” (CARES) which evaluated the cardiovascular safety of febuxostat.

Regulatory Question:

The CARES trial was a multicenter double-blind cardiovascular risk trial published in March 2018.[1] CARES reported a 34% (HR 1.34; 95% 1.03 – 1.73) increase in cardiovascular mortality among febuxostat users compared to allopurinol users. However, since the clinical trial enrolled a high-risk population, it was not clear how generalizable the CARES trial findings were to patients in real world settings. Moreover, 45% of trial patients had incomplete data across the 7-year study and 57% discontinued their assigned medication, casting uncertainty over the estimated magnitude of risk. FDA set out to use Sentinel to examine the characteristics of patients with gout and characterize the utilization of XOIs, including switching patterns of febuxostat and allopurinol.

Results:

We identified over 5 million patients with gout between 2009 and 2016 in Sentinel. Allopurinol was the most commonly used ULT (46.4%), while only a small proportion were febuxostat users (4.3%). Cardiovascular disease risk at baseline was similar between febuxostat and allopurinol initiators, and febuxostat initiators had more severe gout, and were more likely to have chronic kidney disease. Allopurinol initiators also tended to adhere longer to ULT therapy compared to febuxostat initiators. Switching between ULTs was generally low. Compared to CARES, febuxostat users in Sentinel had lower rates of prior myocardial infarction (1.5% vs. 38.6%) and stroke (2.7% vs. 14.8%) and had fewer males (62% vs. 84%).

Regulatory Impact:

The panel remarked that Sentinel provided important real-world data on ULT utilization patterns. Compared to the CARES trial population, Sentinel data suggested that ULT users were older, less likely to be male and had lower gout severity and lower cardiovascular disease risk. This helped support the advisory panel’s determination (19:2 vote, 1 abstain) that there is a patient population in which benefit-risk profile for febuxostat is favorable, and that stronger labeling (a boxed warning for cardiovascular risk), a restricted indication as second-line agent, updating professional society treatment guidelines, and issuing “Dear Healthcare Provider” letters to communicate the risk to patients and their providers, could adequately manage this risk.

[1] White WB, Saag KG, Becker MA, Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout, N Engl J Med. 2018 Mar 29;378(13):1200-1210

Joint Meeting of the Arthritis Advisory Committee (AAC) and Drug Safety and Risk Management (DSaRM) Advisory Committee: Urate-Lowering Therapies and Gout

 

 

Sentinel Data on Estimating Optimal Quantities for Initial Opioid Analgesic Prescriptions for Acute Pain Conditions Featured at Recent FDA Advisory Committee

Mallika Mundkur, MD, MPH; Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD
November 15, 2018

 

In November 2018, FDA held a joint meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee to discuss the definition of opioid-sparing and opioid-replacement analgesics, with a focus on management of acute pain in the post-surgical setting.

To provide the committee with background for discussion, FDA presented recent major guidelines and policies for prescribing opioid analgesics for pain, data describing opioid overdose rates, and range in consumption of opioid analgesics by surgery type. FDA also summarized relevant data from clinical trials, the National Survey on Drug Use and Health and drug utilization data, including analyses of Sentinel data. In this analysis, FDA analyzed data from 17 Sentinel Data Partners to help the committee understand the variation in opioid analgesic use based upon surgery type. The 12 surgical procedures of interest were selected based on regulatory interest and their frequency in the United States.

FDA evaluated prescription durations after surgeries including the days’ supply of the initial dispensing, number of tablets/capsules dispensed, morphine milligram equivalents (MME), and estimated their relationship to probability of “re‐fill.” Results were calculated overall and stratified by surgery, year of the initial dispensing, patient age group, and opioid analgesic of interest. Modeling results were calculated overall and stratified by surgery and age group.

The results suggested that opioid analgesic exposure could be reduced among select surgical populations, particularly those undergoing less invasive procedures, since they had a low frequency of “re-fill.” However, the analysis also suggested that longer initial prescription durations might be appropriate in some cases, and maintaining flexibility in prescribing options is essential to account for variation in opioid analgesic needs by patient as well as procedure.

A verbatim transcript is available approximately 10-12 weeks following the meeting date, in most instances.

Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee Meeting Announcement

Titlesort descending Date Posted
Joint Meeting of the Arthritis Advisory Committee (AAC) and Drug Safety and Risk Management (DSaRM) Advisory Committee: Urate-Lowering Therapies and Gout 01/11/2019
Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee 06/11/2019
Joint Meeting of the Pediatric Advisory Committee and the Drug Safety and Risk Management Advisory Committee: Singulair and Neuropsychiatric Events 09/27/2019
Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee: Development of Opioid‐Sparing and Opioid‐Replacement Drugs 11/15/2018
Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee: Makena Use during Pregnancy 10/29/2019
Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee: Saxagliptin and Cardiovascular Outcomes 04/14/2015
Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee: SGLT-2 Inhibitors and Diabetic Ketoacidosis 01/17/2019
Meeting of the Medical Imaging Drugs Advisory Committee: Gadolinium Retention Following Contrast MRI and Pregnancy Utilization 09/08/2017