Intramural Research Program Administrative Review Followup Barry Hoffer, M.D., Ph.D. Director, Division of Intramural Re

1. Intramural Research Program Administrative Review Followup Barry Hoffer, M.D., Ph.D. Director, Division of Intramural Research, NIDA February 4, 2009

2. Administrative Review On April 17–18, 2008, the Director of the National Institute on Drug Abuse (NIDA), Nora D. Volkow M.D., convened the NIDA Scientific Director Administrative Review Committee, composed of members from the National Advisory Council on Drug Abuse and prominent scientists from the drug abuse and addiction field. The charge to this committee was to provide an administrative review of Dr. Barry Hoffer’s contributions as Scientific Director of NIDA’s Intramural Research Program (IRP).

3. NIDA Scientific Director Administrative Review Committee Daniele Piomelli, Ph.D., Committee Chair Professor of Pharmacology and Biological Chemistry University of California, Irvine Peter W. Kalivas, Ph.D. Professor and Chair, Department of Neurosciences Medical University of South Carolina Mary Jeanne Kreek, M.D. Patrick E. and Beatrice M. Haggerty Professor, Head of the Laboratory of the Biology of Addictive Diseases The Rockefeller University Richard Nakamura, Ph.D. Deputy Director, National Institute on Mental Health National Institutes of Medicine Linda J. Porrino, Ph.D. Professor, Department of Physiology and Pharmacology Wake Forest University School of Medicine

4. The Review Committee made the following recommendations on ways to further improve the IRP: Communication and Cooperation 1. Increase the transparency of decision-making processes. 2. Increase chance (“water-cooler”) interactions among IRP scientists. • Utilize tools of social network analysis to enhance interactions among IRP scientists. Conducting Human Research on Drug Abuse 4. Improve recruiting for protocols. 5. Improve interactions with the NIH Institutional Review Board. 6. Enhance supervision of the contract with the Maryland Psychiatric Research Center. 7. Extend collaborations with clinical investigators at other NIH Institutes for more effective use of the NIH Clinical Center. • Consider alternative venues for clinical research. Cultural Diversity among IRP Researchers 9. The committee wishes to emphasize that Dr. Hoffer has done a tremendous job at supporting the scientific success of minority researchers within the IRP. Still, given lingering perceptions regarding cultural diversity at the NIH, it is important that he continues to maintain a high level of vigilance on this delicate issue.

5. Communication and Cooperation The actions outlined below address all three recommendations Recommendations: • Increase the transparency of decision-making processes. • Increase chance (“water-cooler”) interactions among IRP scientists. • Utilize tools of social network analysis to enhance interactions among IRP scientists. Actions: • Continue with “open door” policy to work directly with staff member on any issue of concern • Established Quarterly Town Hall meetings for all IRP staff – Address issues such as funding, new initiatives, new management processes/policies, announcements, awards • Established Monthly Branch/Section Chief meetings – Scientific presentation with potential for collaborations. Management issues presented and discussed • Supports activities to improve employee engagement Employee of the month award Combined Federal Campaign fundraisers – book/DVD sale and bake sale Holiday Celebration • Established Workgroup looking into creating websites for the PIs • Created a position of “Associate Director for Translational Research to help advise on these issues (Amy Newman) • Supports Chief, AMB, working one-on-one with PIs to develop ideas to help with these issues • Weekly “Clinical Rounds” talks are advertised to all staff in the IRP • Supported workgroup to explore creating a Tobacco-Free workplace • Encourages maximum participation in NIDA HQ interest groups: Comorbidity Bridging Science and Business Current topics in AIDS Behavioral science Nicotine/Tobacco

6. Communication and Cooperation (continued) The actions outlined below address all three recommendations Recommendations: • Increase the transparency of decision-making processes. • Increase chance (“water-cooler”) interactions among IRP scientists. • Utilize tools of social network analysis to enhance interactions among IRP scientists. Actions (Continued): • Encourages participation in relevant seminars given by NIDA extramural or other ICs in NIH • Mini Symposium conducted – all IRP staff encouraged to attend • Training made available to all staff, especially geared toward trainees. In cooperation with Sharon Milgram, NIH Office of Intramural Education and Training “How to fund your NIH training Proposal” Statistical Analysis: “Statistical Strategies for Small Samples” “Academic Job Search Research and Teaching Statements” workshop “Giving a Science Talk” workshop “Job Hunt Strategies” workshop Goal is to have a workshop per month – working on Grant writing now • Encouraged maximum participation in the Annual Bayview Research Symposium which is attended by 400-500 people • Encourages maximum participation in the Hopkins Bayview Lecture series • Supports a weekly NIDA/IRP Seminar Series by providing funding for the speakers and encouraging maximum participation • Supports attendance of trainees at the NIH sponsored one-on-one career training • Creating an email distribution list for trainees to work with each other on issues such as lectures, training opportunities, areas of mutual interest, lunch, after-hour activities, etc.

7. Conducting Human Research on Drug Abuse Recommendation: 4. Improve recruiting for protocols. Actions: • Identified areas in the screening process that could be made more efficient and work better for the research candidate as well as the NIDA study teams. • Flow in the screening process • Efficiencies in identifying all studies for which a candidate might qualify • Internal communications • As a result of our findings and efforts, we were able to achieve: • More streamlined and efficient screening process from phone screen to in-person screening to clearance • More participants involved in more studies and across branches • Increased communication between Recruiting staff and study teams • Looked at recruiting and outreach and worked closely with the Clinical Directors as well as the IRB to create IRB acceptable and effective materials. • Expanded shopping mall based outreach and placement of signage in eye catching areas to boost recognition of NIDA. • Participated in area substance abuse conferences and outreached to community providers to increase exposure for the Archway Clinic. • Created NIDA research studies website which contains information about the protocols we recruit for. • Comparison of Medical Clearanceresults 2007vs. 2008. Note the increase reflected in the 2008 numbers below:

8. Conducting Human Research on Drug Abuse (continued) Recommendation: 4. Improve recruiting for protocols. (continued) Actions: • Advertising and Outreach • NIDA recruitment website approved Feb, 2008 and URL added to all advertisements • Expanded outreach efforts to include treatment centers and colleges • Developed Protocol Summaries with IRB approval for all active studies • Continuously running targeted print ads for all user groups • Phone screening • Streamlined the phone screen process with IRB approved changes • Improved database branching logic to better assist phone screeners in pre-qualification and assessment of callers who may be eligible for more than 1 study • Improved procedure for appointment reminder calls • Appointment reminder letter with directions and map approved by IRB and in use • Improved support for DC callers (e.g. phone support and unique materials created) • Cross training of staff: In-person screeners able to log into Call Center to provide back up to call staff at busy times • In-person screening • Streamlined the in-person screen process • One day instead of 2 day screening for most studies • Screening for multiple studies rather one study at a time • Cross-training of staff: Call staff provides back up to In-person screeners for select tasks • Increased communication between screening staff, study teams and MRP’s • Medical Clearance Process • Implemented Study Assignment Meetings: recruitment staff and study teams meet on a regularly scheduled basis to coordinate the path of participants cleared for multiple studies • Increased communication between recruitment staff, study teams and MRP’s • Established support from recruiting staff for scheduling the study consent appointments • Retainer fees made available for candidates if study team schedules are backed up

9. Study Team Dec 1, 2006- Nov 30, 2007 Dec 1, 2006- Nov 30, 2008 · · Archway/Treatment (385 - B, 385 - C, 390, 3 protocols 5 protocols · · 407, 426) Average census: 25 Average census 40 Kenzie Preston · · CPTB (357, 409, 411, 420, 425, 430, 434) 5 protocols 5 active protocols · · Steve Heishman 12 consented into 411 2 upcoming protocols · 34 consented into 411 · · CDMS/CPTRB (364, 410, 423) 1 protocol 4 protocols · Marilyn Huestis 410: from 10/07 to 11/08 586 screening appointments were made, 259 candidates were screened, 13 participants were admitted · · Molecular Neurobiology (148, 381) 2 protocols 2 protocols · · George Uhl 148: 184 participants 148: 196 participants · · NRB (371, 372, 376, 379, 380, 384, 399, 14 protocols 18 protocols · · 406, 418, 439 ) Users, smokers and controls Users and smokers, very few controls · · Elliot Stein Completed 384 406: 64 participants consented · 406: 36 participants consented · · Archway/Non - Treatment (403, 433) 1 protocol 2 protocols · · Kenzie Preston 403: 13 participants 403: 21 participants consented · consented On - site recruiting for 433 Conducting Human Research on Drug Abuse (continued) Recommendation: 4. Improve recruiting for protocols. (continued) Actions: • Using the techniques described in the previous slide, the number of protocols and the number of participants has increased in every study. • There are now more candidates approved for studies, to such an extent that in some cases the number of referrals is straining the study team’s capacity to book candidates in a timely way.

10. Conducting Human Research on Drug Abuse (continued) Recommendation: 4. Improve recruiting for protocols. (continued) Actions: • The NIDA Clinical Director has worked with the MPRC support and professional staff as well as MMG to develop a auxiliary NIDA-IRP recruitment station in West Baltimore at MPRC on the Spring Grove Campus • The NIDA screening protocol has been modified and approved by the UMB IRB to all participant and patient screening at this site. • The existing infrastructure constructed for the NIDA/MPRC contractual collaboration has been adapted for new recruitment activities. • The Clinical Director, with the NIDA IRP staff, has forged an agreement with the University of Maryland at Baltimore County (across Wilkins Ave from MPRC) in Catonsville to enable active recruitment for students and staff for NIDA IRP research studies. • This site will expand outreach for participant recruitment into West Baltimore with close access to West Side Baltimore County, Howard County and northern Anne Arundel County. • The MPRC staff will bring their considerable expertise in evaluation and recruitment of participant with major mental illness to enhance the prospective pool of research applicants. This will be very important as the number of NIDA/MPRC collaborative studies increases.

11. Conducting Human Research on Drug Abuse Recommendation: • Improve interactions with the NIH Institutional Review Board. Actions: • Clinical Director and/or Deputy Clinical Director meet with the Chair of the IRB regularly • Protocol approval process has been agreed to, formalized and streamlined • NIDA invited to participate in the Executive Steering Committee of the Combined NeuroScience (CNS) IRB • NIDA IRP uses the same protocal tracking software as the rest of the CNS IRB • Memorandum of Understanding for providing support to the Chair of the IRB completed • Membership of IRB augmented to include people who understand NIDA’s unique mission and research – substance abuse expertise is found in NIAAA representation on the NIDA IRB • Ongoing discussions with MPRC IRB and NIH Office of Human Subjects Research for a release agreement for IRB dual reviews – similar to the MOU with JHU • Data Safety Monitoring Board close to being established working with the IRB Chair

12. Conducting Human Research on Drug Abuse (continued) Recommendation: • Enhance supervision of the contract with the Maryland Psychiatric Research Center Actions: In July 2005, the NIDA entered into a 5 year contractual agreement with the MPRC to collaboratively provide: • Residential research and support services • Clinical and medical services • Dual diagnosed psychiatric and substance dependent research volunteers • Facilities and infrastructure designed to accommodate specific research activities Dr. Carlo Contoreggi, M.D. serves as the NIDA Project Officer Dr. Deanna Kelly, Pharm. D. serves as the MPRC Principal Investigator

13. Conducting Human Research on Drug Abuse (continued) Recommendation: • Enhance supervision of the contract with the Maryland Psychiatric Research Center (continued) Actions: • Change in leadership at the MPRC has helped strengthen relationship with NIDA • Clinical Director and Deputy Chief, AMB spend Tuesdays at the MPRC site to provide clinical and management oversight • Scientific Director has met several times with management officials from the MPRC to outline his expectations of the program • All protocols are approved by NIDA Scientific Review and NIDA IRB as well as UMB IRB and DHMH IRB • The number of approved protocols has increased dramatically • A Scientific Liaison (Alane Kimes) has been established whose role is to be responsible for integrating areas and determining commonalities of research between NIDA and MPRC clinical and pre-clinical work. This has provided for: • Substantial initiative in moving forward translational research between pre-clinical investigators and both institutions and integrating bench-to-bedside proposals resulting in 7 on-going collaborations • Professional level oversight to guide investigators through administrative processes which might otherwise limit or slow down collaborative efforts. This also helps to break down institutional barriers that inhibit collaborations • Integration of cooperation from MPRC investigators with meetings, journal clubs, discussions, and progress reports. • Ensuring facilities/personnel are in place for proper patient placement

14. Conducting Human Research on Drug Abuse (continued) Recommendation: • Enhance supervision of the contract with the Maryland Psychiatric Research Center (continued) Actions: Specifically the NIDA and MPRC have collaborated to: • Establish the BSU (Brief Stay Unit), domiciliary accommodations where individuals participating in NIDA-MPRC protocols can be housed up to 14 days. • Recruit highly qualified research nurses, research associates, technicians, and IT support staff • Renovate the NIDA wing of the Spring Grove State Hospital Tawes Building designed to include smoking chambers, participant testing and interview rooms, participant overnight rooms and lounge, toxicology lab, observed lavatories, staff offices and a separate dedicated entrance for staff and participants. • Establish and perform a high number of collaborative clinical and translational protocols. • Establish the NIDA Clinical informatics system at MPRC

15. Conducting Human Research on Drug Abuse (continued) Recommendation: • Enhance supervision of the contract with the Maryland Psychiatric Research Center (continued) Actions: • MPRC has awarded a sub-contract to the Matthew Media Group to design and establish a major NIDA -MPRC participant recruitment initiative from the Spring Grove campus.  • An established recruitment base on the west side of Baltimore will allow NIDA and MPRC the opportunity to target a different socio-economic population than our current east Baltimore base.

16. Conducting Human Research on Drug Abuse (continued) Recommendation: • Enhance supervision of the contract with the Maryland Psychiatric Research Center (continued) Actions: Clinical protocols - 12 collaborative protocols addressing a dual-diagnosed population are currently being conducted at MPRC • INFLUENCE OF NICOTINE ON COGNITIVE FUNCTION IN SCHIZOPHRENIC PATIENTS WITH AND WITHOUT COMORBID DRUG DEPENDENCE (E. HONG-C. MYERS) • QUITTING MARIJUANA USE: SELF-REPORT STUDY OF QUITTING STRATEGIES AND WITHDRAWAL (D. KELLY-D. GORELICK) • DOPAMINE FUNCTION AND REWARD PROCESSING IN SCHIZOPHRENIA (E. HONG-E. STEIN) • NEUROIMAGING STUDIES OF NEUROPHYSIOLOGICAL PHENOTYPES IN SCHIZOPHRENIA (E. HONG-E. STEIN) • A COMPARISON OF VARENICLINE AND PLACEBO FOR SMOKING CESSTATION IN SCHIZOPHRENIA (E. WEINER-A. COFFAY) • KNOWLEDGE OF SMOKING CONSEQUENCES AND VIEWS OF SMOKING AND CESSATIONAMONG PEOPLE WITH SCHIZOPHRENIA (D. KELLY-S. HEISHMAN) • ANTAGONIST-ELICITED CANNABIS WITHDRAWAL (D. KELLY-M. HUESTIS) • PREVENTATIVE HEALTH CARE SERVICES AND FREQUENCY OF MEDICAL DISORDERS IN WOMEN WITH SCHIZOPHRENIA AND SUBSTANCE ABUSE (D. KELLY-C. MYERS) • RASAGILINE IN THE TREATMENT OF PERSISTENT NEGATIVE SYMPTOMS OF SCHIZOPHRENIA (R. BUCHANAN-D. GORELICK) • ALLELIC LINKAGE IN SUBSTANCE ABUSE (D. BOGGS-G. UHL)

17. Conducting Human Research on Drug Abuse (continued) Recommendation: • Enhance supervision of the contract with the Maryland Psychiatric Research Center (continued) Actions: 14 more are “in the hopper” awaiting some level of approval (IRB, budget, scientific review) • EFFECTS OF SMOKING CUES ON TOBACCO CRAVING RESPONSES AND THE REINFORCING EFFICACY OF CIGARETTES IN SMOKERS WITH AND WITHOUT SCHIZOPHRENIA (D. KELLY-S. HEISHMAN) • THE EARLY TIME COURSE OF SMOKING WITHDRAWL IN SCHIZOPHRENIC AND HEALTY SMOKERS: THE EFFECTS OF VARENICLINE (K. WARREN-C. MYERS) • RISK PERCEPTION IN DRUG-DEPENDENT ADULTS WITH AND WITHOUT SCHIZOPHRENIA (K. PRENTICE-D. GORELICK) • TRANSCRANIAL MAGNETIC STIMULATION (TMS) INTERFERENCE WITH CUE-INDUCED NICOTINE CRAVING (H. HOLCOMB-D. GORELICK) • PILOT STUDY OF REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (RTMS) IN THE TREATMENT OF MAJOR DEPRESSIVE SYMPTOMS IN SCHIZOPHRENIA (D. BOGGS-D. GORELICK) • PILOT STUDY OF TRANSCRANIAL MAGNETIC STIMULATION (TMS) INTERFERENCE WITH CUE-INDUCED COCAINE CRAVING (H. HOLCOMB-D. GORELICK) • PILOT STUDY OF TRANSCRANIAL MAGNETIC STIMULATION (TMS) INTERFERENCE WITH CUE-INDUCED CANNABIS CRAVING (H. HOLCOMB-D. GORELICK) • NEUROBIOLOGY AND PHARMACOKINETICS OF ACUTE MDMA ADMINISTRATION (H. HOLCOMB-M. HUESTIS) • OXYTOCIN AND COGNITIVE-BEHAVIORAL THERAPY IN DRUG DEPENDENCE (D. KELLY-M. LEE) • OXYTOCIN IN THE TREATMENT OF SCHIZOPHRENIA WITH COGNITIVE BEHAVIORAL THERAPY (D. KELLY-M. LEE) • SCREENING PROTOCOL FOR THE EVALUATION OF RESEARCH PARTICIPANTS (D. KELLY-D. GORELICK) • EFFECTS OF PROPRANOLOL ON RESPONSES TO DRUG-RELATED IMAGERY SCRIPTS (D. KELLY-K. PRESTON) • ENDOPHENOTYPIC STUDY OF NICOTINE DEPENDENCE IN SCHOZOPHRENIA AND BIPOLAR DISORDER FAMILIES (G. THAKER-C. MYERS) • EFFECTS OF TRANSDERMAL NICOTINE ON AREAS OF IMPAIRED AND PRESERVED FUNCTIONING IN SCHIZOPHRENIA (B. HAHN-E. STEIN)

18. Conducting Human Research on Drug Abuse(continued) Recommendation: • Enhance supervision of the contract with the Maryland Psychiatric Research Center (continued) Actions: Translational protocols - recently undertaken through the contract. The impetus for this undertaking was a desire to take advantage of wealth of scientific personnel available between the two programs to implement basic science proof of principal studies for eventual clinical applications. To date, seven basic science protocols have received approval to be conducted via the contract. • ROLE OF PEDUNCULOPONTINE AND LATERODORSAL TEGMENTAL ACETYLCHOLINE NEURONS IN REWARD PROCESSING (G. ELMER-R. WISE) • TRANSLATIONAL NEUROIMAGING OF HABENULOMESENCEPHALIC REWARD PATHWAYS IN THE RAT (P. SHEPARD-E. STEIN) • METHAMPHETAMINE NEUROTOXICITY AND GENE EXPRESSION IN BCL-2 TRANSGENIC MICE (M. VOGEL-J. CADET) • TESTING GENE BY ENVIRONMENT INTERACTIONS IN AN AMIMAL MODE OF SCHIZOPHRENIA (J. KOENIG-M. LEE) • PHENOTYPING COMORBIDITY (G. ELMER-B. HOFFER) • INVOLVEMENT OF ALPHA-7 NICOTINIC ACETYCHOLINE (7 nACh) RECEPTORS IN CANNABANOID REWARD (R. SCHWARTZ-S. GOLDBERG) • QUANTIFICATION OF N-ACETYL-ASPARTYL-GLUTAMATE (NAAG) IN THE BRAIN (L. ROWLAND-Y.YANG)

19. Conducting Human Research on Drug Abuse(continued) Recommendation: • Extend collaborations with clinical investigators at other NIH Institutes for more effective use of the NIH Clinical Center. Actions: • Clinical Director participating in the NIH PET cGMP and Radiochemistry Research Executive Steering Committee – looks at how NIH ICs can fund and utilize a facility built in the NIH Clinical Center • NIDA IRP participating with NIMH and NIAAA in a protocol at the NIH CC - “Chronic Cocaine Use, Metabotropic Glutamate Receptor 5 Density, Genetics and Craving” • Developing a collaboration with NIDDK on a project at the clinical center which looks at addiction in relation to obesity • Clinical Director attends monthly meetings of the NIH Medical Executive Committee (MEC) composed of all NIH Clinical Directors • Clinical Director involved with the NIH Deputy Director of Intramural Research in a project to explore “Barriers to Clinical Science” • Regular attendance by Clinical Director, Deputy Clinical Director and/or staff from their office at lectures, meetings and grand rounds at the NIH Clinical Center in the area of Radiology and Imaging Sciences

20. Conducting Human Research on Drug Abuse(continued) Recommendation: 8. Consider alternative venues for clinical research. Actions: • The SD has encouraged collaboration between the clinical research program and NIDA extramural programs. He has supported the Deputy Clinical Director (DCD) as she is detailed to work on a Center for Clinical Trials Network (CCTN) project on Post-Traumatic Stress Disorder (PTSD) and Substance Use Disorders (SUD) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) warriors and veterans. • As a research administration mentor, he is encouraging the DCD to explore possibilities of organizational collaborations (DoD, VA, NIH, NIDA) to develop a broad, translational research program to study co-occurring mild Traumatic Brain Injury (mTBI), PTSD, and SUD in OEF/OIF warriors and veterans. • In order to broaden the numbers of patients with co morbid substance abuse disorder liaisons with the Baltimore Veteran Administration Hospital are developing to recruit certain with substance abuse and psychiatric conditions such as PTSD and anxiety and major depressive disorders. • Working with NIDA Director on a project involving collaboration with the Johns Hopkins Medical Institution involving PET and MRI imaging of tobacco users • Study with US Naval Hospital, San Diego; University of Pittsburgh; and Ionworks, Inc. – to develop innovative field-deployable tools that measure exposures to PTSD and mTBI. • Studies using field-deployable hand-held computer devices: • With Johns Hopkins Unviersity, School of Medicine to measure exposures to psychosocial stress and addictive substances • With Johns Hopkins Bloomberg School of Public Health to study the relationship between self-reported emotions, behavior, influences, environment and weight change.

21. Cultural Diversity among IRP Researchers Recommendation: • The committee wishes to emphasize that Dr. Hoffer has done a tremendous job at supporting the scientific success of minority researchers within the IRP. Still, given lingering perceptions regarding cultural diversity at the NIH, it is important that he continues to maintain a high level of vigilance on this delicate issue. Actions: • Secured funding for 4 additional minority trainees • Continue to invite a representative from OEODM and a minority representative to serve on our scientific search committees. • Continue to support a minority summer student program • Supports Women Scientist Advisory council • Combining with NIA • Sponsored a “tea” as a way to discuss future plans • Created honorary award which will be distributed along with a series of lectures in March, 2009 • Combine with NIDA Extramural to do the following: • Utilize the NIH Office of Equal Opportunity & Diversity Management’s Special Emphasis Program Managers when advertising appropriate positions • Continue our relationship with the Society for Advancement of Chicanos & Native Americans in Science (SACNAS) to post our scientific vacancies. • Establish contracts with other minority-focused professional societies to post our vacancies on their websites (i.e., the National Association of Asian American Professionals and the National Organization for the Professional Advancement of Black Chemists and Chemical Engineers.) • Utilize the new Diversity Notification service being offered by NIH HR. HR has developed a listing of 444 diversity organizations (HBCUs, professional associations and societies, etc.) and during the recruit process we can specify which ones we’d like to contact about our vacancy and HR will send an email to them.   • Establish a relationship with Gallaudet University and periodically host a hearing impaired student. • Identify minority scientific/professional societies that will be meeting in the D.C./Baltimore area and sponsor booths or otherwise disseminate information on our vacancies. • Send representatives to the Blacks in Government annual meeting