1. Comparative Effectiveness Research in the National Drug Abuse Treatment Clinical Trials Network (CTN) CDR Steven Sparenborg, Ph.D., Udi Ghitza, Ph.D., CAPT Betty Tai, Ph.D. The Center for the Clinical Trials Network National Institute on Drug Abuse Rockville, Maryland

2. What is CER? A rigorous evaluation of the impact of available treatment options for a given medical condition and particular set of patients. The goal is to determine which specific types of patients would benefit most from a given healthcare option.

3. What is CER? relative medical benefits/risks of available options similar treatments may be compared two or more competing drugs surgery vs. drug therapy may include assessments of cost-effectiveness.

4. Why pay attention to CER? CER has the potential to contain future healthcare spending and improve the quality of care. Therefore, many proposals to reform health care call for an expanded role for CER. CER rises in prominence as attention to healthcare increases. Federal Coordinating Council for CER created in 2009. Patient Protection and Affordable Care Act signed in 2010.

5. Study Types Used in CER randomized controlled trial cohort study case control study cross section study case series systematic review

6. The Clinical Trials Network established in 1999 by The National Institute on Drug Abuse nearly 12,000 patients in nearly 30 trials in dozens of sites located in most states currently 16 nodes centered in academic/VA institutions each node works with 5 or more local community treatment programs funded by 5-year grants

7. The Clinical Trials Network: Purpose and Goals validation and comparison of science-based addiction treatments results guide community-based drug addiction treatment practitioners promote translation of scientifically-derived findings from research to practice conduct and advance comparative effectiveness research (CER) led by community-based practitioners and academic researchers

8. Project 1: Opioid Detoxification 13-day detoxification program (Ling et al., 2005) 113 in-patients and 231 out-patients 6 sites in each condition (i-p; o-p) buprenorphine/naloxone (BUP/NX) vs. clonidine randomized 2:1 subject presence on Day 13 with negative urine sample was considered Tx success

9. BUP/NX was 3-5 times more effective than clonidine

10. Project 2: Motivational Incentives Tx-seeking drug abusers randomized to routine care with or without motivational incentives routine care in community outpatient psychosocial clinics (Petry et al. 2005) routine care in community methadone maintenance clinics (Peirce et al., 2006) low-cost prize-based incentives for drug abstinence

11. Abstinence-based motivational incentives led to improved drug-abstinence outcomes

12. Cost-Effectiveness Analyses Compared to usual care in counseling-based drug-free clinics, the incremental cost of using motivational incentives to lengthen the longest duration of continuous stimulant and alcohol abstinence by 1 week was $258, and to obtain an additional stimulant-free urine sample was $146.

13. Cost-Effectiveness Analyses…cont Compared to usual care in methadone- maintenance clinics, the incremental cost of using abstinence-based incentives to lengthen the longest duration of continuous stimulant and alcohol abstinence by 1 week was $141, and to obtain an additional stimulant-free urine sample was $70.

14. Possible Future CER Studies in the CTN Co-morbidity of Opiates and Alcohol Abuse (in collaboration with NIAAA) patients with opiate abuse/dependence and co- morbid alcohol abuse/dependence randomized to treatment with 1)Suboxone plus an anti-alcohol medication (topiramate, acamprosate, or naltrexone) 2)Suboxone alone, or 3)The selected anti-alcohol medication alone 12 weeks Tx with follow-up 12 weeks after the cessation of pharmacotherapy

15. Possible Future CER Studies in the CTN Smoking Cessation Pharmacotherapy Options assess the effectiveness of nicotine replacement therapy, bupropion, and varenicline as aids to smoking cessation multi-site randomized clinical trial with adaptive design cost-effectiveness analyses all participants will receive smoking cessation counseling primary endpoint will be smoking cessation

16. Conclusions The CTN is an ideal organization to conduct CER studies. CTN investigators and staff are informed and experienced. The CTN infrastructure is designed to promote real-world relevant research that can inform clinicians and policy makers on the best evidence- based interventions for treating drug addiction.

17. Federal Coordinating Council on CER Comparative effectiveness research is the conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat and monitor health conditions in “real world” settings. The purpose of this research is to improve health outcomes by developing and disseminating evidence-based information to patients, clinicians, and other decision-makers, responding to their expressed needs, about which interventions are most effective for which patients under specific circumstances.

18. Federal Coordinating Council on CER To provide this information, comparative effectiveness research must assess a comprehensive array of health-related outcomes for diverse patient populations and subgroups. Defined interventions compared may include medications, procedures, medical and assistive devices and technologies, diagnostic testing, behavioral change, and delivery system strategies. This research necessitates the development, expansion, and use of a variety of data sources and methods to assess comparative effectiveness and actively disseminate the results.

20. In the Future.... generate some near-term results and momentum for the future facilitate the building of needed infrastructure expand access to existing infrastructure demonstrate proof of concept for implementation efforts

21. Patient Protection and Affordable Care Act creates an independent Patient-Centered Outcomes Research Institute a non government entity establishes research priorities funds comparative clinical effectiveness research communicates results to the public requires openness, transparency, and scientific integrity requires patient protections against misuse of research results by policymakers

22. sparenborgs@nida.nih.gov