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Every person has experienced pain in one form or another, and every experience of pain is unique for an infinite number of reasons. The variability, complexity, and risk of abuse can make executing clinical trials for new opioid analgesics a complicated process to plan and manage.

Pain is a ubiquitous consequence of a wide range of injuries, surgeries, and medical conditions as diverse as cancer, low-back pain, and restless leg syndrome. Both acute and chronic pain can be extremely debilitating clinical conditions, and there is an ever-present need for analgesic medication. Those patients whose pain is so severe that it requires chronic opioid administration frequently have complex medical conditions, and often react unpredictably to pain medications. Consequently, pain assessments in these patients is highly challenging, even with the use of well-validated tools.

Then there is the added complexity of prescription opioid abuse. Diversion of opioids—in which prescription drugs are traded illegally—is a frequent issue across the clinical trial setting. This problem occurs across different countries, at multiple investigative sites, and varies by study subjects and study staff.

Potential patients for opioid analgesia trials therefore have complex characteristics, and current study designs are often perceived as highly restrictive and unattractive with regard to eligibility criteria, requirements for a placebo arm, and schedule of events. Pro-active operational risk mitigation and planning can increase compliance and quality of study data, and protect patients and the wider community from the damaging effects of opioid diversion.

To clarify these challenges and to help the industry begin to craft new strategies for managing opioid clinical trials, Quintiles analyzed opioid data from an internal, proprietary, illustrative database using de-identified, aggregated data from many sources. The study also included a leadership survey and follow-up interviews with researchers of opioid analgesia to yield 'lessons learned.'

Diversion, compliance and design

Not surprisingly, analysis of the three main sources of available data confirms there are many challenges associated with conducting opioid trials:

  • Opioid diversion is frequently encountered, particularly with immediate release formulations. Diversion has been encountered with subjects, site staff, and from physical breach of opioid storage. This has major implications for study quality, safety of subjects, and contribution to the social impact of illegal narcotic use in the community.
  • Ensuring compliance is challenging at a subject and site level. At the subject level, diary requirements are onerous, and therefore eligibility and endpoints can be significantly impacted. At the site level, challenges with compliance pertain to accountability of opioid IP and rescue medication. This process is required to be rigorous as this is a key regulatory and safety requirement.
  • Study design currently creates significant barriers to recruiting subjects. These include: strict entry criteria, placebo control, requirement for washout of concomitant analgesics prior to enrolment, complex schedules requiring cumbersome dose titration, and commitments to keep a diary.

None of these findings is earth shattering, but they do highlight the urgency for commercial analgesic developers to collaborate more closely with researchers and regulators to ensure opioid studies are conducted to robust standards in order to assess efficacy and safety accurately. Sub-standard operational execution affects patient safety data quality, and has negative implications for public health. Proactive operational risk mitigation can mitigate many of these risks, while maximizing the safety and efficiency of future opioid clinical trials.

 

For recommendations on how to mitigate the challenges associated with opioid studies, please read: Design and Operational Challenges when Executing Opioid Trials: Lessons Learned

Topics in this blog post: Biopharma, Clinical Trials, CNS, Neurology