In 2021, 17,000 people died from prescription opioid overdose across the U.S.

Letter Text (PDF)

Washington (September 22, 2023) – Senator Edward J. Markey (D-Mass.), chair of the Senate Health, Education, Labor, and Pensions (HELP) Subcommittee on Primary Health and Retirement Security and a member of the U.S. Commission on Combating Synthetic Opioid Trafficking, and Senator Manchin (D-W.Va.) raised concerns over the U.S. Food and Drug Administration (FDA) using enriched enrollment randomized withdrawal (EERW) studies. EERW studies have been used to investigate opioid treatment options for patients with chronic pain but carry the risk of biasing outcomes in favor of opioid approvals. The ongoing opioid epidemic which has claimed the lives of more than a quarter of a million Americans due to prescription opioid overdoses, was fueled in part by pharmaceutical companies and consulting firms intentionally misleading consumers and regulators into believing that these addictive drugs were safe, by employing suspect research practices like EERW.

From members of Congress to medical experts and researchers, concerns have been raised about the safety and validity of EERW studies. According to an FDA-commissioned report, EERW studies underestimate opioids’ adverse impacts. In April, members of the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) criticized EERW studies for their potential risk of harming participating patients by introducing opioid use to patients who were previously not using opioids, prescribing and maintaining opioid doses at their highest tolerance level, and then abruptly stopping opioid use, which can induce withdrawal.

In their letter to the FDA, the senators wrote, “The potential harm of EERW studies is avoidable. According to the FDA’s report, EERW study designs are limited in their ability to inform results more generalizable to a broader population and, particularly with drugs such as opioid analgesics that are widely used and have a wide range of public health impacts, are less informative than other trial designs. Other studies have already evaluated prolonged opioid use without biasing the outcome or exposing patients to risk.”

They continued, “Based on the risk associated with EERW studies and the availability of other study models, we ask the FDA not to permit the use of EERW to determine the long-term efficacy and tolerability of opioids in chronic pain patients. We also urge you to reject EERW study designs for any future new drug applications for opioids and reconsider past opioid approval decisions using EERW. For too long, drug manufacturers have been given the benefit of the doubt in developing and marketing a drug that unleashed a widespread, decades-long epidemic. Using a study model that risks continued bias in favor of approval is unacceptable.”

In July, Senator Markey applauded the inclusion of his bipartisan and bicameral Department of Defense Overdose Data (DOD) Act as part of the National Defense Authorization Act (NDAA) to record military overdoses, protect service members, and military families living with substance use disorder. In June, Senators Markey and Rick Scott (R-Fla.), along with Senators Marco Rubio (R-Fla.) and Thom Tillis (R-N.C.) and leaders of the House of Representatives’ Bipartisan Mental Health and Substance Use Task Force, announced a bipartisan resolution to designate June 6th as Naloxone Awareness Day. In March, he and his colleagues introduced their bipartisan, bicameral Modernizing Opioid Treatment Access Act, legislation that would improve access to methadone, a substance use disorder medication treatment, by modernizing outdated rules. In December, Senator Markey secured provisions of his bipartisan Opioid Treatment Access Act (OTAA)—legislation that reduces wait times for patients qualifying for methadone medication treatment and expands access to methadone clinics—into the end-of-year omnibus spending package.