1. Andrea Denicoff, RN, MS, ANP Clinical Investigations Branch, CTEP, DCTD CTEP Program Meeting March 18, 2009 CTEP Phase III Cancer Treatment Trials with PROs & HRQOL Endpoints

2. Purpose Describe the breadth of currently active Phase III NCI-supported disease treatment trials that include HR-QOL secondary endpoints and compare the characteristics of these trials with those implemented in the early 1990s.* *Nayfield S, Hailey BJ, McCabe M: Quality of life assessment in cancer clinical trials. Report of the Workshop on Quality of Life Research in Cancer Clinical Trials, July 16-17, 1990. Bethesda, MD: US Department of Health and Human Services, 1991.

3. Methods A search was conducted in May 2008 of NCI’s CTEP clinical trials database using the terms: –Active cancer treatment trial –Phase III trial –QOL endpoint –Protocol title –Lead cancer/disease –QOL instrument name PRO & HRQOL instruments were grouped according to their primary measurement focus under the headings: –General QOL (EQ-5D, MOS, PEDSQL 4.0) –Cancer-Specific QOL (FACT, EORTC) –Functional Assessments (CPT, CVLT, WRAT) –Pain & Symptom Management (BPI, MDASI) –Depression/Other Emotional States (BASC, HADS)

4. Results: 1990 vs. 2008 Active Phase III Clinical Trials Cancer Type 1990 Number of Trials 2008 Number of Trials Pediatric Tumors47 Breast38 GYN24 Lung25 Hematologic22 Bladder10 Head & Neck12 Prostate19 Colorectal04 Myeloma03 Melanoma01 Metastases01 Trials with QOL components 1646 Pediatric vs. Adult4 / 127 / 39 Different QOL Tools961

5. PRO & HRQOL Instruments: 2008 Percentage by Primary Measurement Focus

6. Most Commonly Used Instruments in Active 2008 Phase III Treatment Trials

7. Numbers of QOL Instruments Used in Active 2008 Phase III Trials * Neurotox Assmt: includes measures of neurocognitive function, neurotoxicities QOL Tools Used per Trial QOL w/ Neurotox Assmt* QOL w/out Neurotox Assmt* # of Trials Adult 391029 Average # of Tools Adult 2.83.52.5 # of Trials Pediatric 752 Average # of Tools Pediatric 8.710.44.5

8. Results Since 1990, there has been a 3-fold increase in the number of trials with a QOL endpoint along with a 3-fold increase in QOL measurement tools. 62 instruments are being used in these trials to assess the patient’s perspective; often multiple measures are used in a single trial (172 used in total including subtypes). 66 instruments/subtypes are found in the 7 pediatric trials, accounting for 38% of the total amount seen in these trials. Of the 46 trials, the FACT and its various disease and symptom subscales (lung, neurotoxicity, etc.) are used the most frequently (21%).

9. Conclusions In addition to assessing HRQOL and PRO differences among treatment arms in phase III trials, more tools are being used to measure the effects of cancer treatment on function. With the increased use of symptom-specific assessments on trials, there has been a subsequent increased attention on ways to use these data to develop intervention trials. This will lead to improved QOL for patients, as well as assist clinicians and patients in the treatment decision making process.