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Part II


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Part II

  1. 1. Children’s Health Research Summit Session 4: Clinical Research & Clinical Trials Sharon Murphy & Dan Hale, Co-Chairs January 2008
  2. 2. Outline - Definitions of Clinical/Translational Research - Importance / Examples / Issues - Survey of Active Pediatric Clinical Research Hematology/Oncology as an Example - Opportunities
  3. 3. Definitions Clinical Research – Involves human subjects, typically in a face-to-face encounter Clinical Trials – Advance knowledge and promote discovery by following a specified protocol to determine safety, risks/benefits, and efficiency Today’s Trials are Tomorrow’s Cures
  4. 4. Objectives of Clinical Trials Phase I The earliest types of studies that are carried out in humans. They are typically done using small numbers of healthy subjects and are to investigate pharmacodynamics, pharmacokinetics and toxicity II Carried out in patients, usually to find the best dose of drug and to investigate safety III Generally major trials aimed at conclusively demonstrating efficacy. They are sometimes called confirmatory trials and, in the context of pharmaceuticals, typically are the studies on which registration of a new product will be based IV Studies carried out after registration of a product. They are often for marketing purposes as well as to gain broader experience with using the new product
  5. 5. Definition of Translational Research “ Translational research transforms scientific discoveries arising from laboratory, clinical, or population studies into clinical applications and practice.” Lab Population New Tools & New Applications Clinic
  6. 6. The Translational Continuum Basic Science Discovery • Promising molecule or gene target • Candidate protein biomarker • Basic epidemiologic finding Early Translation • Partnerships and collaboration (academia, government, industry) • Intervention development • Phase I/II trials Late Translation • Phase III trials • Regulatory approval • Partnerships • Production & commercialization • Phase IV trials – approval for additional uses • Health services research to support dissemination and adoption Dissemination (new drug, assay, device, behavioral, intervention, educational materials, training) • To community health providers • To patients and public Adoption • Adoption of advance by providers, patients, public • Payment mechanism(s) in place to enable adoption The #1 enemy of translational research is IP
  7. 7. Clinical Trials Conduct of Clinical Trails is (largely) within AHCs which have the personnel, infrastructure, compliance NIH Academic Health Centers (AHCs) Pharmaceutical Companies DOD/VA Foundations 501(c)3 corporations Sponsors Hospitals AHCs Community Clinics Doctors’ Offices Locations Single or multi-institutional Consortia and cooperative groups Models
  8. 8. Challenges to Clinical Research in AHCs Pressure to See Patients Insufficient Clinical Revenues Recruiting Trained Researchers Availability of External Support Competition from CROs IRB Process Finding Research Subjects 93% 89% 75% 72% 48% 38% 37% Based on respondents to a survey of US Med Schools Campbell, E.G., et al JAMA 286: 800-806, 2001
  9. 9. Difficulties in Recruiting Children to Clinical Trials Caldwell, P.H.Y., Murphy SB, et al Lancet 364:803-11, 2004 • Primary treating doctor’s reluctance to enroll patients • Lack of awareness of trials for accrual • Parent’s fears of perceived risks and mistrust of researchers • Sociodemographic factors • The child’s health status: The more severe the illness, the greater the willingness to participate • The informed consent process • Inconvenient/unpleasant aspects of trial design
  10. 10. Childhood ALL: Progressive Improvement In event-free Survival 1950-2000 0 1 2 3 4 5 0 20 40 60 80 100 1950 1965 1985 2000 Years From Diagnosis
  11. 11. n          n           EthnicityEthnicity % 5-Yr Survival *% 5-Yr Survival * PHR **PHR ** 4,0614,061 (79.8%)(79.8%) WhiteWhite 81.9%81.9% 1.001.00 518518 (10.2%)(10.2%) AAAA 68.6%68.6% 1.421.42 507507 (10.0%)(10.0%) HispanicHispanic 74.9%74.9% 1.331.33 TotalTotal 5,0865,086 *p < 0.0001 by stratified log-rank test **PHR, proportional hazards ratio, by Cox proportional hazards regression, adjusted for age, WBC, ploidy, gender, era of treatment, or size of treating institution. Conclusion: AA and Hispanic children with ALL have mortality rates 42% and 33% higher respectively than Whites; differences not explained by presenting prognostic factors.
  12. 12. Pediatric AIDS/Lymphoma Network HIV + NHL+ HIV - NHL+ HIV + NHL- Demographic Clinical Molecular Viral Phase I+II Trails - Response - Toxicity Cases Control Comparisons
  13. 13. Survey of Active Clinical Research Protocols in the Division of Hematology/Oncology, Department of Pediatrics, UTHSCSA (2007) • Total Trials = 113, including - 70open Children’s Oncology Group (POG) protocols - 10transplant trials (PBMC, TTI) - 7 industry sponsored, plus various registries, tissue/sera collection, etc. • Enrollments: 79 total, 57 oncology, 22 hematology larger numbers on study, active, in follow-up
  14. 14. Opportunities Further Develop/Expand the Childhood Cancer Survivors Program Relate research in long-term survivors of childhood cancer to long-term outcomes of other childhood illnesses: CF, genetic disorders, heart disease, transplants, diabetes, etc.