Summary: A retrospective analysis shows that 27.8% of pain medications classified as having high abuse potential successfully complete development, compared with just 4.7% of medications judged to have low abuse potential.
Source: American Society of Anesthesiologists
New analysis published in Anesthesiology highlights the low level of investment in pain medication development despite the widespread burden of pain in the United States and the substantial societal costs it creates.
The study’s authors note that the opioid crisis has underscored the urgent need for safer, effective chronic pain therapies with lower abuse potential.
They emphasize that developing new pain treatments is particularly challenging because pain is inherently subjective, and conducting the large-scale clinical trials required for regulatory approval is expensive and time-consuming.
A clearer understanding of the likelihood that new pain medications will succeed would help reduce investment risks and could encourage more research and development in this area, the authors argue.
In a retrospective analysis, Dermot P. Maher, M.D., M.S., M.H.S., assistant professor at John Hopkins University School of Medicine, Baltimore, together with colleagues in financial engineering at the MIT School of Management, evaluated 469 clinical development programs representing 399 unique active pharmaceutical ingredients from 2000 through 2020.
Using publicly available clinical-trial metadata from databases provided by Informa Pharma Intelligence (Citeline), the team estimated probabilities of success, development duration, and program survivorship for pain medication candidates.
The analysis found a notable difference in success rates based on perceived abuse potential: 27.8% of drugs with high abuse potential progressed from phase 1 through approval, while only 4.7% of drugs flagged as having low abuse potential reached approval.
Although the number of programs developing drugs with high abuse potential has decreased since the 2010 peak of the opioid epidemic, those programs still show a higher likelihood of completing development and receiving regulatory approval than programs for drugs with lower abuse potential.
The authors suggest that this disparity may reflect a more mature biological understanding of the pain signaling pathways targeted by traditionally abused drugs, compared with the novel mechanisms pursued by newer, lower-abuse-potential candidates.
“The opioid crisis was a wake-up call for medicine,” said Dr. Maher. He noted that clinicians have long faced a difficult trade-off: patients seeking relief while clinicians lacked therapies that were both consistently effective and free from dependence risks or serious side effects.
Dr. Maher stressed that the findings also show it is possible to develop successful pain medications. He called for targeted research to better understand pain mechanisms and to guide the development of safer, effective treatments that address this unmet medical need.
In an accompanying editorial, Michael S. Sinha, M.D., J.D., M.P.H., and Kelly K. Dineen Gillespie, R.N., J.D., Ph.D., concur with the study’s call for expanded development of pain medications with improved safety profiles. They argue that federally funded research is essential to deepen understanding of pain biology and to translate that knowledge into safer analgesics and nonpharmacologic options.
“The National Institutes of Health (NIH) and other research sponsors must allocate funding toward the development of safer analgesics and nonpharmacologic pain management strategies,” they state, urging continued and expanded support for initiatives such as the NIH Helping to End Addiction Long-term (HEAL) Initiative.
The editorial authors also recommend reforming public and private financing models to better support interdisciplinary, multimodal, and time-intensive pain treatment programs—approaches that improve function and well-being but are underfunded in systems that favor fragmented, intervention-heavy care. They call for increased investment in provider cross-training in pain medicine, substance use disorder treatment, and trauma-informed care, and note that innovative, noninvasive biotechnology may offer promise.
To shift the trajectory of pain management research and care, the authors conclude that coordinated action by key public and private stakeholders across multimodal treatment domains is the most effective way forward.
The authors highlight expanding support for NIH-funded programs and similar initiatives as one practical way to accelerate development of safer pain treatments and to address the public health consequences of opioid misuse.
They also point readers to resources on opioid abuse and non-opioid alternatives provided by professional organizations, noting that coordinated public-health, clinical, and research efforts are necessary to improve pain care while minimizing addiction risk.
About this pharmacology and addiction research news
Author: Theresa Hill
Source: American Society of Anesthesiologists
Contact: Theresa Hill – American Society of Anesthesiologists
Image: The image is in the public domain
Original Research: Open access.
“Estimates of Probabilities of Successful Development of Pain Medications: An Analysis of Pharmaceutical Clinical Development Programs from 2000 to 2020” by Dermot P. Maher et al. Anesthesiology
Abstract
Estimates of Probabilities of Successful Development of Pain Medications: An Analysis of Pharmaceutical Clinical Development Programs from 2000 to 2020
Background
This analysis estimates the probability of successful development and the duration of clinical trials for medications intended to treat nociceptive and neuropathic pain. The authors also examine how the perceived abuse potential of a drug influences these outcomes.
Methods
Using the Citeline database, the study calculated probabilities of success, development duration, and survivorship for pain medication development programs between January 1, 2000, and June 30, 2020. Estimates were conditioned on development phase, pain type (nociceptive vs. neuropathic), and the medication’s abuse potential.
Results
Overall, the probability that a pain medication program progresses from phase 1 to regulatory approval was 10.4% (standard error, 1.5%). Programs for nociceptive pain had a higher probability of success (13.3%, standard error 2.3%) than those for neuropathic pain (7.1%, standard error 1.9%). Medications labeled with high abuse potential had a success probability of 27.8% (standard error, 4.6%), whereas drugs with low abuse potential had a success probability of 4.7% (standard error, 1.2%). The greatest attrition occurred between phase 3 and regulatory approval.
Conclusions
The data indicate that characteristics unique to pain medications—particularly their abuse potential and the type of pain they target—can significantly affect the likelihood and duration of successful development. Understanding these factors can help guide investment, trial design, and research priorities to bring safer, effective pain treatments to patients.