Overcoming the challenges of analgesia trials
Clinical trials in pain indications present unique challenges. Subjects drop out of pain trials for reasons including insufficient pain management and relief, treatment side effects, burden of multiple study visits and assessments and use of rescue medication. Recent studies in chronic and short-term pain report drop-out rates ranging from 5-40%. Missing data resulting from subject drop-outs makes it difficult to interpret the results of pain trials and the impact to drug development programs can be great.
Rho has extensive experience in pain management clinical trials and addressing these challenges to set your program up for success. Here are a few ways we can help you:
Successful outcomes start with a strong trial design. Rho’s experts have designed analgesia-related trials that minimize drop outs, increase study execution efficiency, and lead to robust data analyses. Our experts can help you:
- Strategize to identify the appropriate end points for trials.
- Provide input on when to measure and how to summarize the data. Simplifying assessments and visit frequency will reduce the number of drop outs.
- Explore alternative trial designs. Rho is experienced with a variety of designs beyond standard parallel arm protocols; these include flexible dosing/titration to effect, enriched enrollment randomized withdrawal (EERW), cross-over trials, and add-on safety extensions.
Rho’s project teams are well-versed in the successful execution of analgesia-related clinical trials. We emphasize strategies that facilitate recruitment and maximize retention. Our teams can help you:
- Identify and select high enrolling and quality-driven clinical sites with proven track records.
- Create and implement strategies to increase retention rates by limiting subject burden.
- Implement robust Investigator and clinical site staff training to ensure understanding of the importance of subject retention and complete data.
- Monitor data collection and identify problems with retention and other missing data early, so that issues can be addressed and corrected.
Rho’s experts have years of experience providing analyses to FDA and the Division of Anesthesia, Analgesia, and Addiction Products (DAAAP). We understand the current landscape and expectations related to analgesia data and analyses.
- Rho has experts who can help you navigate suggested guidelines on missing data as outlined in the recently FDA endorsed guidance on missing data from the National Academy of Sciences (NAS), The Prevention and Treatment of Missing Data in Clinical Trials.
- Rho is familiar with the most up-to-date analysis methods for missing data in analgesia-related trials, including:
- Multiple Imputation
- Pattern Mixture Models
- Jump to Control Imputation
- Retrieved dropouts
- Various sensitivity analyses, including last observation carried forward (LOCF), baseline observation carried forward (BOCF), LOCF/BOCF hybrids, mixed-effect model repeated measures (MMRM), delta adjustment, and others.
We can help you select an analysis design that is right for your trial and meets the expectations set by the new NAS guidance document.
Rho has experience with a broad range of pain indications and outcomes, including the following areas:
- Post-operative pain (including bunionectomy and TKA)
- Musculoskeletal pain
- Dental pain
- Gastrointestinal pain
- Neuropathic pain
- Musculoskeletal pain (including chronic lower back pain)
- Osteoarthritis pain
- Cancer pain
- Visual Analog Scales (VAS)
- Sum Pain Intensity Difference (SPID)
- Numeric Pain Rating Scale (NPRS/NRS)
- Likert Scale outcomes
- Western Ontario and McMaster Osteoarthritis Index (WOMAC)
- Brief Pain Inventory (BPI)
- Patient Global Impression of Change (PGIC)
- Responder analyses
- Rescue medications
- Roland-Morris Disability Questionnaire (RMDQ)
- Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate Withdrawal Scale (SOWS)
Click here to view our resources for analgesia trials.