When the Food and Drug Administration (FDA) public advisory committee meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee meets on June 11-12, it will be hearing from some chronic pain advocates.
Richard “Red” Lawhern Ph.D.—who heads the Alliance for the Treatment of Intractable Pain–has filed comments in advance of the meeting. The Committee is designed to provide advice and recommendations to FDA on regulatory issues. Dr. Lawhern warns the committee against doing anything else that can harm patients. Here’s his testimony:
I write and speak widely as a technically trained non-physician advocate for chronic pain communities, with over 60 published papers in both medical journals and mass media. Please place the attachment before all members of both Advisory Committees prior to their meeting.
Published data demonstrate a very wide range of minimum effective dose levels in individual pain patients, due to genetic polymorphism in liver enzymes which govern opioid metabolism. There is no one size fits all patient or therapy plan. Literally millions of US citizens benefit from high-dose opioid therapy with no evidence of addiction or mortality risk. To further restrict availability of high dose opioids in an already profoundly hostile regulatory environment would be both misdirected and abusive of patients.
As noted in greater detail in the attachment, published data from the CDC demonstrate no consistent relationship between overall rates of prescribing by doctors versus overdose-related mortality from all sources. The contribution of medically prescribed opioids to mortality is so small that it gets lost in the noise of illegal street drugs. To the limited extent that there are trend lines in mortality data, they suggest that since 2016, mortality is marginally lower in US States where rates of opioid prescribing are highest. Prior to 2016, trend lines were flat, with correlation coefficients less than 0.05.
Algorithms employed by HHS/CMS to identify potentially at-risk “over-utilizers” of opioids have been shown to have limited predictive value. Over half of all high-dose Medicare patients identified as having elevated risk of substance abuse do not present with such a diagnosis within 18 months. More than half of all overdose-related deaths in one US State occurred in people who had no current prescription.
Studies of the impact of high-dose opioid analgesics on overdose mortality reveal a gross rate of overdose-related mortality at 0.022% per year (22 deaths per 100K), comparable to mortality observed in medications for atrial fibrillation following stroke. While mortality rates rise with dose, there is no distinct “upward knee” threshold in mortality vs dose.
Also, of concern is an historical but unsupported bias against co-prescription of opioids and benzodiazepine drugs. Under-treated anxiety and depression are factors in elevated risk of patient mortality. Yet there are no published observational trials in live patients, to demonstrate actual risk of respiratory depression; all evidence is inferential, drawn from cause of death assignments that are confounded by non-uniform standards among county medical examiners.
Under the principle of “first do no harm”, I urge the Advisory Committees to refrain from recommending further restrictive measures on prescribing. You are dealing with populations so small that direct safety improvements cannot be measured. But the indirect effect of such restrictions will reliably be to further poison the regulatory environment for all pain patients and encourage the departure of medical professionals from pain management.
Cease, halt, and desist.
If you wish to add your comments, you can do so here.