Estimates of Probabilities of Successful Development of Pain Medications

An Analysis of Pharmaceutical Clinical Development Programs From 2000 to 2020

Dermot P. Maher, M.D., M.S., M.H.S.; Chi Heem Wong, Ph.D.; Kien Wei Siah, Ph.D.; Andrew W. Lo, Ph.D.


Anesthesiology. 2022;137(2):243-251. 

In This Article

Abstract and Introduction


Background: The authors estimate the probability of successful development and duration of clinical trials for medications to treat neuropathic and nociceptive pain. The authors also consider the effect of the perceived abuse potential of the medication on these variables.

Methods: This study uses the Citeline database to compute the probabilities of success, duration, and survivorship of pain medication development programs between January 1, 2000, and June 30, 2020, conditioned on the phase, type of pain (nociceptive vs. neuropathic), and the abuse potential of the medication.

Results: The overall probability of successful development of all pain medications from phase 1 to approval is 10.4% (standard error, 1.5%). Medications to treat nociceptive and neuropathic pain have a probability of successful development of 13.3% (standard error, 2.3%) and 7.1% (standard error, 1.9%), respectively. The probability of successful development of medications with high abuse potential and low abuse potential are 27.8% (standard error, 4.6%) and 4.7% (standard error, 1.2%), respectively. The most common period for attrition is between phase 3 and approval.

Conclusions: The authors' data suggest that the unique attributes of pain medications, such as their abuse potential and intended pathology, can influence the probability of successful development and duration of development.


The exact definition and taxonomy of pain has been revised several times by the International Association for the Study of Pain (Washington, D.C.). Broadly, it currently includes nociceptive pain, caused by specialized pain receptors detecting adverse stimuli; neuropathic pain, caused by damage or disease affecting the nervous system; and the recently added category of nociplastic pain, caused by the altered behavior of pain receptors. Many pathologies are composed of overlapping components of two or sometimes all three of these categories.[1] There are many potential causes of pain, such as cancer, inflammation, and tissue injury, as well as injury or lesions of the nervous system. The proportion of adults in the United States reporting at least one painful health condition increased from 120 million (32.9%) in the period between 1997 and 1998 to 178 million (41%) in the period between 2013 and 2014.[2] An estimated 50 to 100 million adults in the United States live with chronic pain that can substantially restrict their work, social, and self-care activities.[3]

Despite the widespread prevalence and high societal costs of both pain and addiction, investment in therapeutics in both areas remains underfinanced. This has taken place for a variety of reasons, not least of which is the poor understanding of the probability of successful development of pain medications.[4] A poor understanding of the probability of successful development prevents accurate modeling of the risks involved in pain pharmaceutical development and could lead investors and drug developers to instead pursue safer, more well-understood therapeutic areas. An accurate understanding of the probability of successful development of new pain medications would remove part of the unknown risks of investment in this space, which could further increase growth and lead to a more robust pipeline of new pain medications. Additionally, a knowledge of probabilities of successful development will help anesthesiologist and pain physicians, many of whom are very active in the drug development process, to better focus research and academic efforts.

The opioid crisis has highlighted the need for new therapeutics with low abuse potential to treat chronic pain. While pharmaceutical companies recognize this need, because of the subjective nature of pain—in addition to poorly defined phenotypes of pain response in human populations, a general lack of reliable biomarkers, and the high placebo response—the conduct of clinical trials for new drug approval in this space is a lengthy and costly proposition.[3] While there are numerous risks involved in the development of new pain treatments, an understanding of the potential opportunities in this field will hopefully encourage further development.

This study examines the outcomes and parameters of clinical development programs for pain medications. We first compute the individual probability of successful development for pain medication development programs between 2000 and 2020. We then analyze them by the type of pain treated (nociceptive vs. neuropathic) and the abuse potential of the medications. We then examine the duration and survivorship of these clinical trials across their various phases and outcomes. Our results allow for improved financial allocation and pipeline optimization in this therapeutic area.