Perhaps the Seedy Sea storm is past, the weather is clearing, and the CDC will arise once again as a respectable organization to address opioid safety concerns for patients, clinicians, caregivers, and public health at large.
Over the last several months my recent and current student pharmacists and post-graduate doctoral pharmacy residents have been following the Center of Disease Control issues regarding the proposed guidelines. During their rotations or longitudinal training, they continued to care for challenging patients that were referred to our pain clinic for management of persistent unrelenting chronic pain.
Most of these young clinicians spent just a few weeks with me, while others have spent a bit more, up to almost 7 months. Several of them approached me with a desire to share their experiences and insight with the CDC by responding to the guidelines at The Centers for Disease Control and Prevention (CDC) Notice: Federal Register Notice: Proposed 2016 Guideline for Prescribing Opioids for Chronic Pain.
Update: Total number of comments on Federal Register when closed to comments on January 13, 2016 was 4012.
They did a phenomenal job and kept it fair balanced! Here is their entire response letter as it appears on the Federal Register…
This response to the “Proposed 2016 Guideline for Prescribing Opioids for Chronic Pain” comes from a group comprised of seven Student Pharmacists, three Post Graduate Year 1 (PGY1) Pharmacy Residents, and one Post Graduate Year 2 (PGY2, Pharmacy Resident with specialty training in Pain and Palliative Care). For clarification, the four residents all have earned PharmD degrees and the student pharmacists are candidates from several different colleges of pharmacy. All authors have spent four or more weeks under the mentorship of Dr. Jeffrey Fudin, a Clinical Pharmacy Specialist in Pain Management and Director or a PGY2 Pain and Palliative Care Residency program. All undersigned have participated in direct patient care with focus in ambulatory care chronic noncancer pain. This response has been reviewed in detail by Dr. Jeffrey Fudin in advance of submission.
Pain is often the chief complaint that causes patients to seek medical care and is a prevalent comorbidity of various acute and chronic conditions. Chronic pain affects up to 126 million Americans1,2, which represents more than diabetes3, heart disease4, and cancer5 combined, yet chronic pain remains inadequately managed for a multitude of reasons, not the least of which is poor education in schools of medicine and pharmacy. The proposed CDC draft guidelines for opioid prescribing will likely have a tremendous negative impact on millions of patients. We extend our heartfelt condolences to those who lost a beloved friend or family member to an opioid overdose and we sympathize with the millions of Americans affected by chronic pain. However, we believe that the issues addressed by the CDC guidelines are multifaceted and require zealots on each side of the “opioid-camp” come together to improve outcomes for patients rather than to sensationalize issues that most notably require study and more evidence. Well-trained clinicians in the fields of pharmacy and medicine working collaboratively could help alleviate some of the stressors encountered by patients, improve outcomes, and foster better pain care while mitigating opioid risks.
Upon review of the Proposed 2016 Guideline for Prescribing Opioids for Chronic Pain we find various contradicting statements based on the presented evidence and the recommendation strength. According to the National Guideline Clearinghouse, “level A rating requires at least two consistent Class I studies”.6 However, all of the 12 recommendations provided are based on case series (level 3 evidence) or expert opinion (level 4 evidence) yet assigned a grade A recommendation.7 For instance according to the proposal, providers “should implement additional precautions when increasing dosage to ≥50 morphine milligram equivalents (MME)/day, and should generally avoid increasing dosage to ≥90 MME/ day (recommendation category: A, evidence type: 3)”. The recommendation is based on one randomized unblinded study8 in 135 patients (94% males; 74% have musculoskeletal pain) who received 40 MME/day compared to 52 MME/day, yet the recommendation was generalized to “chronic non cancer pain” and recommended “to avoid increasing dosage to ≥90 MME/ day” which was not evaluated by the referenced study.
To assign a cut-off of morphine 90mg per day, we believe is over-simplified and may propose challenges in practice. The proposed guidelines recommend a standardized MME, or a “morphine maximum dose” sometimes abbreviated MMD, but did not recommend a standardized method for calculating morphine equivalence. Not surprisingly, there is a wide variability among opioid conversions including, but not limited to online opioid dosing calculators. Rinnick A and others that included nationally renowned pain experts, compared equianalgesic conversion estimates as calculated by practicing clinicians, by surveying 411 healthcare professionals; 129 physicians, 213 pharmacists, and 69 nurse practitioners.9 After adjustment for statistical inclusion, 319 participants were incorporated in the final analysis. Participants were asked to provide the morphine equivalent for hydrocodone 80mg, fentanyl 75mg/hour (1800mcg/day), methadone 40mg, oxycodone 120mg, and hydromorphone 48mg. Participants were also asked to provide the resource used for their calculation. MME for fentanyl, hydrocodone, hydromorphone, methadone, and oxycodone were: 176 (±117) mg, 88 (±42) mg, 192 (±55) mg, 193 (±201) mg, and 173 (±39) mg, respectively. The authors stated “A total of 124 (46%) respondents identified using personal knowledge as a resource for their conversion problems, followed by use of an online calculator at 83 (31%), a textbook table at 45 (17%), and a conversion table from a journal at 15 (6%).
Considering the Rennick study, it is of particular importance that the standard deviations for fentanyl and methadone “morphine equivalents” will exceed the CDC cut-off by CDC’s own definition of morphine equivalent. In other words, the current CDC guidelines suggest that patients should not receive more than a 50 MME and not to exceed 90 MME. But by Rennick’s findings, a calculation for fentanyl 7.5mg patch would be up to 117 MME less than and 117 MME more than the 7.5mg (75mcg/hour) fentanyl dose. What does this mean? Looking at this another way, one clinician’s MME in this case could be 59 MME and another clinician might assign the equivalence of 293 MME, a range spanning 234mg of morphine equivalent. Just the standard deviation alone is a recipe for death in the untrained professional.
Given lack of standardization, potential drug interactions, patient’s physical features such as height and weight, gender, end organ (dys)function, coupled with patient individualized pharmacokinetics due to polymorphism, we respectfully disagree with utilizing a standard cut-off for morphine dose. We suggest that the CDC give credence to these mathematical and physiological variabilities and employ efforts to mandate education for providers and to approach every conversion for each individual patient slowly and carefully.
We believe that increasing awareness of the opioid overdose risk is appropriate, but claiming certain unsubstantiated risks outweigh the benefits of using opioids to treat pain lacks scientific foundation. According to a recent study by Dasgupta et al., of 2,182,374 patients prescribed opioids, 478 overdose deaths were reported (0.022% per year).10 Over the past 2 years, there have been recent studies by Dr. Barbara Zedler et al. that identified risk factors associated with overdose or serious opioid-induced respiratory depression.11,12 The authors used a multivariable linear regression model to assign a score to each identified risk factor and to calculate a risk index for overdose or serious opioid-induced respiratory depression (RIOSORD) score. The calculated total RIOSORD score corresponds to an average predicted probability of opioid-induced respiratory depression of 2% to 84%. The risks taught by this regression analysis should be considered by all prescribing clinicians – the sad truth is that most prescribers don’t even know the RIOSORD model exists.
We firmly believe the problem is a lack of training and education on opioid prescribing; instead of improving the knowledge of healthcare professionals, the guideline is placing the burden on patients by reducing opioid access for patients that may legitimately require them. There is a deficit in the education provided on pain management in medical and pharmacy schools. A study by Mezei L et al. concluded that education for North American medical students is limited, variable, and often fragmentary.”13 Over 80% of attending physicians rate their education on chronic pain during medical school as “inadequate”.13 Another study by Yanni et al. identified lack of confidence in treating chronic pain among physicians, where 59% of the participants rated the education on pain management as “fair” or “poor”.14 As for opioid abuse, the National Center on Addiction and Substance Abuse at Columbia identified that 67% of primary care providers do not screen for substance abuse, 83.1 feel unprepared to detect aberrant drug-related behaviors, and about 70% are unprepared to detect prescription drug abuse.15,16
This lack of emphasis on pain management is also prevalent in the pharmacy school curricula. A qualitative assessment of pharmacy school faculty members found that out of 28 pharmacy schools, 21 (75%) believed that “too little” emphasis was being given to pain management.17 There are only 8 accredited PGY-2 training programs for pharmacists on pain management and palliative care in the U.S, which pales compared to the prevalence of chronic pain.18 To put this in further perspective, as of November 2015, there were 1158 PGY1 general practice residency programs and 853 PGY2 specialty practice programs throughout the US. Pain residencies for pharmacists are represented by less than 0.4% of all residency training programs and 1.4% of all specialty training programs. This is grossly out of proportion when matched against disease prevalence and other common medical conditions. We believe there is a knowledge and training deficit across the pain management continuum among all healthcare professionals, and increasing the emphasis on pain education beginning early on in their training and continued throughout their practice years could be a major step towards safe and effective pain management.
We believe the implementation of the CDC guidelines may have a drastic negative impact on patients living with pain and their loved ones. The Proposed 2016 Guideline for Prescribing Opioids for Chronic Pain recommendations may place restrictions on personalized patient care and prevent clinicians from providing high quality of care. We believe that management of persistent pain requires a multidisciplinary team including but not limited to physicians, physician extenders, pharmacists, and behavioral health clinicians, all of whom who provide overlapping and synergistic services. The variability in opioid conversion tools, altered pharmacokinetics; polypharmacy, and drug-drug or drug-food interaction potential, could all complicate medication management within the chronic pain population. Therefore, we believe that improving education and fostering a multimodal approach in pain management is a reasonable and responsible approach.
- Mena Raouf, Doctor of Pharmacy Candidate 2016, Albany College of Pharmacy and Health Sciences
- Lisa Dragic, Doctor of Pharmacy Candidate 2016, Temple University School of Pharmacy
- Jacqueline Pratt Cleary, PharmD, PGY-2 Pain and Palliative Care Resident, Albany NY
- Alireza Shamsali, Doctor of Pharmacy Candidate 2016, Albany College of Pharmacy and Health Sciences
- Mazen Saeed, 2016 PharmD/MBA Candidate, Albany College of Pharmacy and Health Science
- Uyen Nguyen, Doctor of Pharmacy Candidate 2016, Western New England University College of Pharmacy
- Jeffrey Bettinger, Doctor of Pharmacy Candidate 2017, Albany College of Pharmacy and Health Sciences
- Phillip Boglisch, PharmD/MBA Candidate 2016, Western New England University College of Pharmacy
- Steven Sparkes, PharmD, PGY-1 Pharmacy Resident, Albany NY
- Daralyn Morgenson, PharmD, PGY-1 Pharmacy Resident, Albany NY
- Joni Carroll, PharmD, PGY-1 Pharmacy Resident, Albany NY
Statements made are the opinions of all signatories and do not reflect the opinion of any listed affiliations. The information contained herein was not prepared as any part of participant government duties.
- National Institutes of Health. Estimates of Pain Prevalence and Severity in Adults. August 2015. https://nccih.nih.gov/news/press/08112015
- Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research. The National Academies Press, 2011. http://books.nap.edu/openbook.php?record_id=13172&page=1.
- American Diabetes Association. http://www.diabetes.org/diabetes-basics/diabetes-statistics/
- Heart Disease and Stroke Statistics—2011 Update: A Report From the American
- American Cancer Society, Prevalence of Cancer:
- Dowell D. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. Regulations.gov. Available at: http://www.regulations.gov/#!documentdetail;d=cdc-2015-0112-0002. Accessed April 2016. = http://www.regulations.gov/#!documentDetail;D=CDC-2015-0112-0002
- Naliboff BD, Wu SM, Schieffer B, et al. A randomized trial of 2 prescription strategies for opioid treatment of chronic nonmalignant pain. J Pain 2011;12:288–96.
- Rennick A, Atkinson T, Cimino NM et al. Variability in Opioid Equivalence Calculations. Pain Med. 2015 Sep 9. doi: 10.1111/pme.12920. [Epub ahead of print]
- Dasgupta N, Funk MJ, Proescholdbell S. et al. Cohort Study of the Impact of High-dose Opioid Analgesics on Overdose Mortality. Pain Medicine 2015
- Zedler B, Xie L, Wang L, et al. Development of a risk index for serious prescription opioid-induced respiratory depression or overdose in Veterans’ Health Administration patients. Pain Medicine. 2015 Jun;16:1566-79.
- Zedler B, Saunders W, Joyce A, et al. Validation of a screening risk index for overdose or serious prescription opioid-induced respiratory depression prescription opioid use and deaths from overdose or opioid-induced respiratory depression. Presented at the 2015 AAPM Annual Meeting. March 2015.
- Mezei et al. Pain Education in North American Medical Schools. The Journal of Pain, 12:12 (December), 2011: 1199-1208
- Yanni LM, et al. Preparation, confidence, and attitudes about chronic noncancer pain in graduate medical education. J Grad Med Educ 2010 (2):260–268
- National Center on Addiction and Substance Abuse at Columbia. Missed opportunity: national survey of primary care physicians and patients on substance abuse. Columbia University, Center on Addiction and Substance Abuse 2000. Available at: http://www.casacolumbia.org/templates/Publications_Reports.aspx#r41. Accessed September 21, 2012.
- Zacharoff KL. The Role of Education in Safe and Effective Pain Management. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/UCM337162.pdf
- Singh RM, Wyant SL. Pain management content in curricula of U.S. schools of pharmacy. J Am Pharm Assoc (Wash). 2003 Jan-Feb;43(1):34-40.https://accred.ashp.org/aps/pages/directory/residencyprogramsearch.aspx