PROP’s Disproportionate Influence on U.S. Opioid Policy: The Harms of Intended Consequences
A recent study by the Centers for Disease Control and Prevention (CDC), published on February 12, 2021, in the Morbidity and Mortality Weekly Report (MMWR), has sent ripples through the palliative care and chronic pain communities. The report highlighted a staggering 1,040% increase in age-adjusted overdose death rates involving synthetic opioids, psychostimulants, cocaine, heroin, and prescription opioids between 2013 and 2019. This alarming statistic has ignited debate, with critics pointing to the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain and its subsequent misapplication as significant contributors to this surge in overdose fatalities. At the heart of this controversy lies Physicians for Responsible Opioid Prescribing (PROP), an advocacy group whose policy approach over the past decade has faced scrutiny for allegedly limiting access to legitimate opioid medications and inadvertently contributing to the escalating overdose crisis in the United States. This analysis delves into PROP’s trajectory, its influence on national policy, and the unintended consequences that have emerged.
The Genesis of PROP and its Early Policy Stance
The origins of Physicians for Responsible Opioid Prescribing (PROP) can be traced back to 2011, when a group of internists, including Michael Van Korff, Andrew Kolodny, and Roger Chou, co-authored a seminal article that many in the palliative care field would later recognize as a critical turning point in opioid policy discussions. In this publication, they announced the formation of PROP, a self-proclaimed "nonprofit organization with no pharmaceutical industry funding or ties," dedicated to identifying "practical approaches to more cautious opioid prescribing in community practice." They argued that "Guidelines for long-term opioid therapy should not be developed by the field of pain medicine alone," advocating instead for a collaborative approach involving experts from general medicine, addiction medicine, and pain medicine to "increase the margin of safety." This foundational statement set the stage for PROP’s future advocacy, emphasizing a precautionary principle in opioid prescribing.
PROP’s Landmark Petition to the FDA and the Subsequent Backlash
PROP’s first significant attempt to shape national opioid policy came in July 2012, with the submission of a petition to the Food and Drug Administration (FDA) requesting critical changes to the labeling of opioid analgesics. The petition, signed by prominent figures including PROP President Andrew Kolodny and Vice-president Michael Van Korff, alongside other medical specialists, sought three primary alterations:
- Elimination of "moderate" pain indication: The petition called for striking the term "moderate" from the indication for non-cancer pain, effectively limiting the clinical use of opioid analgesics solely to severe cancer pain.
- Establishment of a maximum daily dose: A maximum daily dose of opioid analgesia, equivalent to 100 milligrams of oral morphine (MME), was proposed for the treatment of all non-cancer pain.
- Imposition of a 90-day treatment limit: The petition requested a maximum duration of 90 days for continuous (daily) opioid analgesia use for non-cancer pain, after which opioid therapy would be discontinued.
The FDA acknowledged receipt of the petition on July 26, 2012, and it garnered a letter of support from Representative Mary Bono Mack of California on the same date. However, the unity among the petition’s supporters proved short-lived. Concerns were quickly raised by the palliative care and pain management communities regarding the potential for reduced access to essential opioid therapy for patients with legitimate pain needs.
Dr. Stu Gitlow, President of the American Society of Addiction Medicine (ASAM) and a signatory to the petition, issued a statement clarifying ASAM’s position. He emphasized that the relabeling proposals were "not intended, in any way, to limit a chronic pain patient’s access to clinically appropriate opioid pain therapy or to impinge upon a pain specialist’s ability to make individual decisions regarding the most effective therapy for their legitimate pain patient."
Prominent pain management experts also voiced significant concerns. Bob Twillman, Director of Policy and Advocacy for the American Academy of Pain Management (AAPM), criticized the 90-day limit as "arbitrarily chosen" and pointed out that the FDA’s standard for opioid trials was typically 12 weeks, not longer studies as implied by PROP’s critique of long-term efficacy. Dr. Russell Portenoy, a palliative medicine physician, expressed apprehension that the petition’s signatories might possess an "incomplete understanding of opioid pharmacology and pain medicine," potentially leading to regulatory changes detrimental to public health.
Several medical professional organizations echoed these sentiments. The American Society of Anesthesiologists (ASA) questioned the clarity of defining cancer pain, asking who would delineate between cancer-related pain and pain resulting from treatment. The American Academy of Pain Medicine (AAPM) stated that the petition’s rationale was "seriously flawed, potentially harmful to patients with debilitating pain conditions for whom opioid therapy is indicated, and without substantive scientific foundation." Similarly, the American Pain Society (APS) cited "insufficient scientific evidence base" and expressed concern that mandated indications, dosing, and duration would lead to "untreated pain and loss of access to individualized care."
The FDA’s Measured Response and PROP’s Shift in Strategy
On September 10, 2013, the FDA issued its response to the PROP petition, granting some requests while denying others. The agency agreed that "more data are needed about the safety of long-term use of opioids" and mandated post-approval studies for extended-release/long-acting (ER/LA) opioid analgesics to assess risks such as misuse, abuse, hyperalgesia, addiction, overdose, and death. The FDA also required safety labeling changes to communicate these risks more effectively and clarify the appropriate patient population for ER/LA opioids, including a new boxed warning.
However, the FDA rejected PROP’s most significant proposals. The agency found no scientific support for separating non-cancer from cancer pain in labeling, stating that "a patient without cancer, like a patient with cancer, may suffer from chronic pain." The proposed 100 mg MME daily dose limitation was also denied, as the scientific literature did not support such a threshold, and it could falsely imply a superior safety profile below that limit. Finally, the FDA deemed the request for a 90-day maximum treatment duration "not supportable" based on the presented evidence.
Despite the FDA’s partial rejection of its core demands, PROP publicly framed the petition as a success and continued to advocate for a 100 mg/day MME limit. Recognizing the FDA’s resistance, PROP began to explore other avenues to influence opioid policy, including engaging with the Federation of State Medical Boards (FSMB) to encourage changes in their model policy on opioid prescribing. Ultimately, PROP identified a more receptive federal partner: the Centers for Disease Control and Prevention (CDC).
The CDC Guidelines: A New Frontier for PROP’s Influence
In September 2015, the CDC announced its intention to draft Opioid Prescribing Guidelines. This move presented PROP with a new opportunity to shape national policy. However, the drafting process quickly became a source of contention. Critics raised concerns about a lack of transparency, particularly the CDC’s failure to disclose all outside advisors consulted. An unusually short, 48-hour comment period for stakeholders added to the apprehension.
Deeper concerns emerged when it was revealed that at least five PROP Board Members, including then-President Jane Ballantyne and founder Andrew Kolodny, had served on panels involved in developing the CDC Guidelines. Jane Ballantyne, in particular, was the sole clinician from the pain management community on the CDC Core Expert Group.
Medical professional organizations and patient advocacy groups voiced strong criticism. The American Medical Association (AMA) highlighted concerns about the lack of transparency in the review process and called for a more balanced panel with broader clinical representation. The Patient Quality of Life Coalition (PQLC), representing numerous palliative care and hospice organizations, lamented that the Guideline appeared "devoid of empathy for patients who need legally-prescribed opioid medications for relief from serious and long-lasting pain."
In response to the outcry for transparency and broader clinical input, the CDC extended the comment period to 30 days. This delay, however, was met with frustration by PROP founder Andrew Kolodny, who worried it would "tack months on to the process" and increase the likelihood of the guideline never being released, which he termed "an enormous win for the opioid lobby."
Publication and Early Criticisms of the CDC Guidelines
Despite these controversies, the CDC Opioid Prescribing Guidelines were published in the MMWR on March 18, 2016. While many in primary care found the guidelines useful, concerns persisted among pain experts about their potential misapplication and broader impact on patient populations. Patrice Harris, then AMA board chair-elect, expressed concerns about the evidence base, potential conflicts with existing laws and product labeling, and "possible unintended consequences," such as insurance coverage limitations for non-pharmacotherapeutic pain options. Bob Twillman, executive director of AAPM, found the guidance lacking, particularly regarding dosage and duration limitations, fearing that "some clinicians will interpret these ‘soft limits’ and thresholds as absolute ceiling doses, and that people with pain will suffer needlessly as a result."
Adding to the internal dissent, a group of CDC scientists, identifying as the "CDC Spider Group (CDC Scientists Preserving Integrity, Diligence and Ethics in Research)," expressed integrity concerns in August 2016, alleging that "our mission is being influenced and shaped by outside parties and rogue interests" and that "CDC data were clearly manipulated in irregular ways" for political purposes. Similar allegations of compromised data collection due to corporate and political influence surfaced in other publications. Despite these warnings, the 2016 CDC Opioid Prescribing Guidelines were implemented as planned.
Unintended Harms and the Growing Backlash
By 2018, two years after the guidelines’ release, it became increasingly evident that their misapplication was contributing to significant harm. An article by CDC scientists in April 2018 challenged the methodology used to estimate opioid overdose deaths, arguing that the CDC’s traditional method overestimated deaths related to prescription opioids by failing to account for the rise of illegally manufactured fentanyl (IMF). Using a more conservative method, the estimated number of prescription opioid-involved deaths in 2016 dropped from 32,445 to 17,087, highlighting a critical need for accurate data differentiation to inform public health efforts.
Beyond data accuracy, the misapplication of the CDC guidelines led to a rise in suicides linked to forced or involuntary tapers off opioid analgesics, both within and outside the Veterans Affairs Healthcare System. Although the CDC intended the guidelines as non-mandatory guidance for primary care physicians, legislators, pharmacy chains, and insurers seized upon certain recommendations and translated them into rigid limits.
This widespread misapplication prompted the American Medical Association (AMA) to pass a resolution in November 2018. The AMA affirmed that some patients might benefit from opioid doses exceeding the CDC guideline recommendations, advocating against the misapplication of the guideline by various entities and stating that MME thresholds should be used only as guidance, not as sole grounds for professional discipline or penalties.
In the wake of the AMA’s stance, other clinical leaders and medical societies amplified calls for action against forced opioid tapering. In February 2019, leading cancer organizations sent a joint letter to the CDC seeking to address "unintended implementation and reimbursement consequences." While the CDC acknowledged that the guideline was "not intended to deny any patients who suffer from chronic pain from opioid therapy," and encouraged clinical judgment, the response was perceived by many as insufficient.
FDA and CDC Clarifications Amidst Growing Concerns
The escalating concerns surrounding the misapplication of the CDC guidelines culminated in significant announcements in April 2019. On April 9, the FDA issued a safety announcement warning against the sudden discontinuation or rapid dose reduction of opioid pain medications, citing reports of serious harm including withdrawal symptoms, uncontrolled pain, psychological distress, and suicide. This was followed by a coordinated effort from the CDC to address the misapplication of its own guidelines.
On April 24, the CDC issued a media release advising against several problematic interpretations of its 2016 Guideline, including:
- Misapplication to populations outside the Guideline’s scope.
- Misapplication leading to hard limits or "cutting off" opioids.
- The Guideline not supporting abrupt tapering or sudden discontinuation.
- Misapplication to patients receiving medication-assisted treatment for opioid use disorder.
This statement was accompanied by a companion article in the New England Journal of Medicine (NEJM), co-authored by PROP member Roger Chou. While acknowledging that "some policies and practices purportedly derived from the guideline have in fact been inconsistent with, and often go beyond, its recommendations," the NEJM article also vigorously defended the guidelines, citing their widespread embrace and high-quality rating. Notably, the article included a disclaimer stating that the views expressed were those of the authors and not necessarily the official position of the CDC.
Undeclared Conflicts of Interest and Continued Influence
The ongoing debate surrounding opioid policy was further complicated by revelations of undeclared conflicts of interest among PROP members. In June 2019, Reckitt Benckiser, the manufacturer of Suboxone, an opioid addiction treatment drug, agreed to a record $1.4 billion settlement with the U.S. Department of Justice. Critics had long alleged financial ties between PROP members and Reckitt Benckiser, fueled by past comments from Andrew Kolodny dismissing the company’s pharmaceutical nature. Kolodny had also consistently advocated for buprenorphine (Suboxone) as a primary treatment for opioid addiction in congressional and state hearings.
Further scrutiny revealed that several PROP members failed to disclose relevant conflicts of interest when publishing articles. Andrew Kolodny did not disclose his executive directorship of PROP or his expert witness testimony in opioid-related malpractice cases when publishing in JAMA. PROP President Jane Ballantyne similarly failed to disclose her affiliation with PROP in an article co-authored with other PROP members in the Annals of Internal Medicine. Mark Sullivan, another PROP member, only disclosed his work on an opioid tapering device after participating in a CDC-sponsored activity, despite this work occurring during the drafting of the CDC Pain Guidelines. These instances of under-reporting conflicts of interest raised serious questions about the objectivity of their contributions to opioid policy discourse.
Despite these revelations, PROP members continued to occupy influential positions. Roger Chou, a PROP member and vocal critic of opioid prescribing, was identified as the lead author of a controversial April 2020 AHRQ report concluding that opioids were no more effective than non-opioid medications for pain and increased the risk of abuse, addiction, and overdose. This report’s findings, which reaffirmed many of the CDC’s disputed conclusions, became particularly concerning as the CDC announced plans to review and potentially revise its 2016 Pain Guidelines.
CDC’s Reassessment and the Ongoing Debate
In April 2020, the CDC opened a public docket to solicit comments on pain management, including the benefits and harms of opioid use. The response was substantial, with over 5,392 comments submitted from patients, physicians, and organizations. The American Academy of Hospice & Palliative Medicine (AAHPM) strongly criticized the misapplication of the 2016 Guideline, detailing "devastating effects on patients and prescribers," including forced tapering, medical deterioration, and suicidality. The AMA echoed these concerns, highlighting that the CDC’s own authors and HHS had acknowledged the guideline’s misapplication and urged the CDC to rescind policies based on hard MME thresholds.
PROP, in its comments, acknowledged a decrease in prescription opioid morbidity and mortality but failed to acknowledge the concurrent rise in illicit drug-related overdoses. They argued that for some patients, continued opioid use was necessary to avoid discontinuation effects, a claim criticized by patient advocates as "gaslighting." PROP also predicted that reduced new starts of chronic opioid treatment would lead to better outcomes, a prediction that proved to be starkly inaccurate in light of subsequent data.
In July 2020, the CDC announced the formation of a new Opioid Workgroup under the Board of Scientific Counselors (BSC/NCIPC) to review the existing guidelines and provide recommendations for an update, anticipated in 2022.
The February 2021 MMWR Report and Inaccurate CDC Data
While the world awaited updated guidelines, the February 12, 2021, MMWR report, detailing the 1,040% increase in overdose deaths, re-ignited the debate. This stark statistic challenged PROP’s assertion that reduced opioid prescribing was a positive development. In response, PROP sent a letter to the AMA President, alleging that the AMA’s opposition to dose and duration guidance was influenced by pharmaceutical industry donations. The AMA President, Susan R. Bailey, countered that the CDC authors themselves had recognized the misapplication of their guidelines and that focusing solely on restriction overlooked the complexity of pain management.
Further undermining PROP’s narrative, an article published in Pain Therapy in March 2021 detailed fundamental methodological flaws in the CDC’s data on prescription opioid overdose deaths. The authors asserted that the CDC had erroneously reported prescription opioid overdose deaths for over a decade by including non-prescribed illicitly manufactured fentanyl and methadone administered for opioid use disorder. This report exposed the flawed premise that overprescribing had driven the overdose crisis, suggesting that the CDC’s coding practices had misled the public.
Andrew Kolodny quickly responded with a webinar refuting alleged "myths and false narratives" about the opioid crisis. However, this presentation was criticized as "gaslighting" pain sufferers and doctors, employing straw man arguments and deflection to create plausible deniability for PROP’s role in contributing to the harms caused by the misapplication of the CDC guidelines.
Conclusion: The Lingering Impact of PROP’s Influence
Despite being rebuffed by the FDA in 2013 due to a lack of scientific evidence, PROP has wielded disproportionate influence on U.S. opioid policy for nearly a decade. By finding a receptive partner in the CDC, PROP played a significant role in shaping the 2016 CDC Pain Guidelines, despite a process that lacked transparency and involved disproportionate representation from PROP members on advisory panels. Even as the CDC and FDA acknowledged the harmful misapplication of the guidelines and warned against forced opioid tapers, PROP doubled down on its rhetoric, dismissing legitimate concerns and encouraging the continued misapplication of the guidelines.
This occurred against a backdrop of repeated instances where PROP members failed to disclose relevant conflicts of interest, including those critical during the drafting of the CDC guidelines. Given this history, it is imperative that PROP’s role in guiding future opioid policy be significantly limited. This is especially concerning as Roger Chou, a PROP member, has been linked to the authorship of new CDC Pain Guidelines, with the CDC again exhibiting a lack of transparency regarding the authors. This continued lack of openness should alarm all who advocate for patient access to pain medications for medically legitimate indications.
Beyond limiting PROP’s influence, questions of culpability arise regarding the harms stemming from the misapplication of the 2016 CDC Pain Guidelines. The legal standard for liability in civil suits requires a preponderance of evidence, meaning it is "more likely than not" that PROP’s advocacy efforts shaped the CDC guidelines, that their subsequent advocacy contributed to their misapplication, and that this misapplication resulted in substantial harm. The ongoing efforts by PROP members to establish plausible deniability in the wake of the February 2021 MMWR report suggest a potential awareness of such liability. A thorough re-evaluation of PROP’s role and impact is crucial to ensure that future opioid policy prioritizes evidence-based care and patient well-being without the undue influence of organizations with a history of questionable practices and undeclared conflicts of interest.
