What Is Needed to Advance Pain Medicine Research? Donna L. Hammond, Ph.D. Department of Anesthesia University of Iowa U NIVERSITY of I OWA Pain Research Program

The Unfortunate Truth Research rarely pays for itself (in $$) Research rarely pays for itself (in $$) It requires an initial up-front investment in people, space and equipment It requires an initial up-front investment in people, space and equipment At best, a “leveraged” venture At best, a “leveraged” venture

The Unfortunate Truth A “leveraged” venture A “leveraged” venture –For a 50K “investment” you get a 250K return –Intangible returns: Enhanced institutional and academic statureEnhanced institutional and academic stature More competitive residency applicantsMore competitive residency applicants MSTP students in departmental laboratoriesMSTP students in departmental laboratories Additional avenues for faculty developmentAdditional avenues for faculty development The opportunity to define academic anesthesiaThe opportunity to define academic anesthesia

Research has to be Balanced Clinical Research M.D. M.D. Ph.D. Ph.D.R.N. Basic Research Ph.D. M.D. Ph.D. M.D. Established Infrastructure

Research Infrastructure Pre- and post award administrator Pre- and post award administrator –Negotiate contracts in consultation with clinical research associates (effective cost recovery) –Facilitates grant submissions, renewals, noncompeting continuations Grant face pages, budget preparation, identify funding sourcesGrant face pages, budget preparation, identify funding sources –Monitors spending of external and internal projects

Research Infrastructure Clinical research associates Clinical research associates –Review contracts for institutional cost of performance –Prepare and coordinate IRB submissions and regulatory documents –Conduct clinical research –Liaison with pharmaceutical companies and clinical research organizations

Clinical Research Enterprise Two avenues: Two avenues: –Hypothesis-driven New knowledge to advance perioperative medicineNew knowledge to advance perioperative medicine –Contract work for pharmaceutical firms $$$ to support research and research infrastructure$$$ to support research and research infrastructure –Both can be conducted in the pain clinic non-competitive and complementarynon-competitive and complementary

Clinical Research Enterprise Hypothesis-driven research: Personnel Hypothesis-driven research: Personnel –M.D. Ph.D. (endangered species) –M.D. with 2-year research fellowship –Savvy mentorship/leadership –Training opportunities –Departmental training grant –Institutional training programs Translational researchTranslational research Clinical investigation (K30 awards)Clinical investigation (K30 awards) Basic science departmentsBasic science departments

Clinical Research Enterprise Pharmaceutical Contracts: Personnel Pharmaceutical Contracts: Personnel –Experienced M.D. or M.D. Ph.D. faculty –Inexperienced or junior faculty –Clinical research nurses –Predetermined protocols MultisiteMultisite Manageable sizeManageable size Limited durationLimited duration

Clinical Research Enterprise Facilities: Operating Room/Ambulatory Surgery Facilities: Operating Room/Ambulatory Surgery –Appropriate for studies of pre- and post- operative approaches to pain relief –Database in place (OR schedule facilitates screening and recruitment of subjects)

Clinical Research Enterprise Facilities: Pain Clinic Facilities: Pain Clinic –Appropriate for studies of chronic pain –Often lacking a well-developed database to categorize, track or “retrieve” patients Billing codes are a poor substituteBilling codes are a poor substitute Necessary to know “true” population of patients before undertaking a study; i.e. is it feasibleNecessary to know “true” population of patients before undertaking a study; i.e. is it feasible –Time constraints often limit studies

Clinical Research Enterprise Facilities: Pain Clinic Facilities: Pain Clinic –Experienced Leadership Intellectual activities have equal importance as clinical care (inherent conflict here)Intellectual activities have equal importance as clinical care (inherent conflict here) –Teamwork All members of the clinic need to be committed to success of the “unit”All members of the clinic need to be committed to success of the “unit” –Staff need to know current protocols and be prepared to enroll subjects –Database can identify patients in advance of their appointment.

Basic Research Enterprise Studies of the pharmacology, physiology, anatomy and molecular biology of both acute and chronic pain mechanisms Studies of the pharmacology, physiology, anatomy and molecular biology of both acute and chronic pain mechanisms Translates bench to the bedside, and the bedside to the bench Translates bench to the bedside, and the bedside to the bench Early recruitment of pre-med and M1 medical students to a career in academic anesthesia Early recruitment of pre-med and M1 medical students to a career in academic anesthesia Train and mentor residents or junior faculty in anesthesia research Train and mentor residents or junior faculty in anesthesia research

Basic Research Enterprise The PhD and the MD PhD (80% effort) as the research engine The PhD and the MD PhD (80% effort) as the research engine Externally-funded research programs Externally-funded research programs –2 RO1/person or 1 K and 1 RO1 award –75% salary recovery of faculty –100% salary recovery of other persons –100% recovery of research expenditures Secondary appointments in basic science departments Secondary appointments in basic science departments

Basic Research Enterprise Strong group of independent scientists with complementary research skills Strong group of independent scientists with complementary research skills –Molecular biology –Cellular physiology –Integrative/systems –Genetics Nucleus of intellectual activity with a strong programmatic theme Nucleus of intellectual activity with a strong programmatic theme Highly interactive/collaborative to link the department to basic science departments and the pain clinicians Highly interactive/collaborative to link the department to basic science departments and the pain clinicians

What Are Some New Directions in Pain Research? Genomics and proteomics: Genomics and proteomics: – gene-chip assays to identify substances that are up- or down-regulated as a consequence of pain Zebrafish: Zebrafish: –vertebrate homolog that can support high throughput screening of drugs that prevent pain- induced changes in gene and protein expression Transcriptional factors and gene regulation Transcriptional factors and gene regulation

What Are Some New Directions in Pain Research? Conditional knock-outs and knock-ins Conditional knock-outs and knock-ins Outcomes research and epidemiology Outcomes research and epidemiology –Defensive position –Evidence-based medicine –Better understanding of the subject Functional imaging Functional imaging –Move beyond the normal subject to the patient –Exploration of sensory and affective aspects of pain

Pain Research Program UNIVERSITY of IOWA Donna L. Hammond, PhD - Anesthesia –Pharmacology, Graduate Program in Neuroscience, MSTP Gerald F. Gebhart, PhD - Pharmacology –Graduate Program in Neuroscience, MSTP Tim Brennan, MD PhD - Anesthesia –Graduate Program in Neuroscience Kathleen Sluka, PT PhD - Physical Therapy –Graduate Program in Neuroscience, MSTP Klaus Bielefeldt, MD PhD - Internal Medicine –Internal Medicine Molecular Biologist, PhD or MD PhD - Anesthesia –Pharmacology Clinical Pain Investigator, MD or MD PhD - Anesthesia