Acute Pain Models in Drug Development

Human pain models have been established as effective, cost-efficient tools for evaluating the efficacy of analgesic drugs. Three acute pain models have been most commonly used in recent years: bunionectomy, third molar extraction and abdominoplasty. Each of these procedures offers unique benefits but also comes with limitations. The third molar extraction model is an inpatient procedure with post-op monitoring for 24-48 hours, high assay sensitivity and rapid enrollment. This model is commonly used for medications with low analgesic potency or as a proof-of-concept model for analgesic medications in development. The abdominoplasty model does not require a disease or a specific diagnosis but has exhibited variability among study participants due to its episodic nature of post-surgical pain and often requires a multi-site approach to meet recruitment objectives. While the third acute pain model, bunionectomy, will be the primary focus of this webinar, we will also discuss the critical factors that distinguish all three acute pain models, such as benefits, limitations, study timelines and cost differences between each model.

The bunionectomy model has been used for more than 25 years to evaluate oral, topical, parenteral and implantable analgesic medications. The variety of completed bunionectomy studies highlights its proven reliability with high assay sensitivity for evaluating analgesia. The post-surgery acute pain model consists of a short, standardized inpatient procedure (30-90 minutes) using different types of anesthesia with post-surgery monitoring ranging from 48 hours to 7 days, depending upon the needs of the study. The procedure involves manipulating many different tissue types, which results in moderate to severe acute pain that typically plateaus for 48-72 hours.

Despite the numerous benefits of this acute pain model, it does come with a few challenges. Adequate and consistent training to reduce variability is a key challenge that encompasses training caregivers and raters. Despite the bunion deformity being a prevalent condition across all populations, recruitment that maintains diversity within the study population can be a difficult challenge to overcome. Two challenges stand out in all three acute pain models. First, each patient has a different pain tolerance, which influences self-reported pain scales. Second, it is crucial to maintain a consistent and controlled environment to reduce variability and confounding factors.

Despite the challenges, the bunionectomy model continues to be a valuable tool with validated clinician-rated and patient-rated assessments for evaluating efficacy and safety of pain management interventions. Clinician-rated evaluations are frequently used to assess safety, such as the Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) and the Columbia-Suicide Severity Rating Scale (CSSRS). Participant-rated assessments are commonly used to evaluate a medication’s analgesic efficacy and include time to onset of perceived and/or meaningful relief as well as pain at rest and pain with movement rated on the Numerical Rating Scale (NRS) or the Visual Analog Scale (VAS). Given its proven track record of success and favorable experimental conditions, the bunionectomy has been the most used acute pain model and is the gold standard for evaluating an analgesic’s efficacy in a controlled environment.

Register for this webinar today to explore the value of acute pain models for evaluating analgesic drug development.

Speakers

Dr. Lynn Webster, MD, Executive Vice President, Scientific Affairs, Dr. Vince Clinical Research

Dr. Lynn Webster is an internationally recognized clinical research expert in pain and addiction medicine. He has participated as an Investigator in hundreds of clinical trials and has authored more than 300 peer-reviewed articles.

Dr. Webster is board-certified in anesthesiology, pain medicine and addiction medicine. He serves as an Editor for Pain Medicine and serves as a peer reviewer of several professional journals. Additionally, he is a grant reviewer for the National Institute of Health.

Dr. Webster has significant expertise in clinical research, with a focus on experimental and human pain models, human abuse potential studies as well as assessing the effects of drugs on respiratory depression.

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Dr. Ira Gottlieb, DPM, Medical Director, Chesapeake Research Group

Dr. Ira J. Gottlieb has over 25 years of experience as a board-certified podiatric surgeon and clinical researcher. He is the founding member of Chesapeake Research Group (CRG) located in Central Maryland. This 8,000 square foot state-of-the-art “3 in 1” facility includes the clinical research site with private room overnight stay capability.

In addition, there are two on-site accredited ambulatory surgery centers where study-related surgical procedures are performed. He has been the Principal Investigator and completed over 150 clinical trials. Dr. Gottlieb specializes in research focused on the relief of painful conditions and is dedicated to finding new medications to help reduce the worldwide opioid epidemic and associated deaths.

He is very proud that his research projects have resulted in the FDA approval of many new and improved pain-relieving medications currently on the market. Although considerable progress has been made towards reducing opioid-related drug deaths in the United States and around the world, there remains more work to be done to achieve the lofty goal of completely eliminating opioid deaths.

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Rose Gerringer, Ratings Manager, Dr. Vince Clinical Research

Rose Gerringer, Ratings Manager, oversees subjective data collection at DVCR. Rose brings 25 years of experience as an instructor in both corporate and academic settings to train staff and volunteers in the collection of primary endpoints for human abuse potential and acute pain models.

Rose’s clinical pharmacology research experience spans 12 years with eight of these in subjective data collection and four in regulatory compliance.

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