# Presentation: 862318

## FDA Arthritis Advisory CommitteeJuly  29, 2002

**Nosology of chronic pain**
**Methodology of efficacy trials**
**Long-term safety**

**Topics for Discussion**

**Thomas J. Schnitzer, M.D., Ph.D.****Professor and Asst. Dean for Clinical Research****Northwestern University Feinberg School of Medicine**

**Notes:**
None of the prophylactic regimens for NSAID-induced serious GI complications are optimal. For example, while misoprostol has proved to protect against gastric and duodenal ulcers in NSAID users, the drug’s adverse effects (e.g., diarrhea) discourage more widespread use.  Also, it is contraindicated in women of childbearing age.

## Methodology: Trial Design

- Analgesia-dependent population
- High levels of pain (>70mm on 100mm VAS)
- “Sub-acute” pain model
- Selects for drugs effective for _acute_ pain

**Flare design**

**Notes:**
None of the prophylactic regimens for NSAID-induced serious GI complications are optimal. For example, while misoprostol has proved to protect against gastric and duodenal ulcers in NSAID users, the drug’s adverse effects (e.g., diarrhea) discourage more widespread use.  Also, it is contraindicated in women of childbearing age.

## OA: Pain Walking on a Flat Surface

- WOMAC (0- to 100-mm VAS)

- Week

**OA: Pain Walking on a Flat Surface**

- 65-76 mm

## Methodology: Trial Design

- Used in pediatric studies, RA guidance
- All subjects receive active medication
- No necessity for disease flare
- No need for artificial definition of “responder”

**Withdrawal design**

**Notes:**
None of the prophylactic regimens for NSAID-induced serious GI complications are optimal. For example, while misoprostol has proved to protect against gastric and duodenal ulcers in NSAID users, the drug’s adverse effects (e.g., diarrhea) discourage more widespread use.  Also, it is contraindicated in women of childbearing age.

## Time to Exit Due to Inadequate Pain Relief

**Time to Exit Due to Inadequate Pain Relief**

**Survival Function**

**0.1**

**0.2**

**0.3**

**0.4**

**0.5**

**0.6**

**0.7**

**0.8**

**0.9**

**1.0**

**0**

**5**

**10**

**15**

**20**

**25**

**30**

**35**

**40**

**45**

**50**

**0**

## Long-Term Safety

- NDA datasets inadequate for uncommon events
- Post-marketing surveillance program required
- Well defined and carefully planned
- Timely completion
- Provide appropriate incentives

**Notes:**
None of the prophylactic regimens for NSAID-induced serious GI complications are optimal. For example, while misoprostol has proved to protect against gastric and duodenal ulcers in NSAID users, the drug’s adverse effects (e.g., diarrhea) discourage more widespread use.  Also, it is contraindicated in women of childbearing age.

## Summary

**Stimulate new approaches**
** ****Different, appropriate methodologies**
** ****Safety and outcomes data**
**Partnership between government, industry, academia and public**

**Notes:**
None of the prophylactic regimens for NSAID-induced serious GI complications are optimal. For example, while misoprostol has proved to protect against gastric and duodenal ulcers in NSAID users, the drug’s adverse effects (e.g., diarrhea) discourage more widespread use.  Also, it is contraindicated in women of childbearing age.