Community Advisory Boards on Repeat: What’s Missing from TB Clinical Trials Protocols L. McKenna2,3, M. Frick1,3, D. Namutamba1, C. Lee1, W. Vandevelde2, M. Low2, E. Lessem2,3 1Community Research Advisors Group (CRAG), 2Global TB Community Advisory Board (TB CAB), 3Treatment Action Group (TAG) LESSONS LEARNED Engaging communities in the clinical trial protocol development process is feasible and effective. Draft TB treatment research protocols routinely fail to address several scientific and ethical concerns, including: plans for results dissemination; plans for post-trial access to investigational products; adequate composition (or even presence) of control arms; use of non-stigmatizing language in study documents; and the appropriate inclusion of key affected groups, including children, adolescents, people with HIV with low CD4 counts, and pregnant women. Following community advisory board (CAB) review, protocols can often be amended to address community concerns. Language addressing common concerns should be considered as routine additions to future protocols. Community reviews of protocols should happen early and often in the protocol development process, ideally when there is still opportunity for meaningful consideration of community feedback and time to make necessary changes to the protocol. BACKGROUND Community engagement is a critical component of research. The tuberculosis (TB) field has only recently begun to solicit community input into clinical trials protocols, and at a stage where feedback can be incorporated. The Global TB Community Advisory Board (TB CAB) and the Community Research Advisors Group (CRAG)— independent groups of research-literate activists—work to ensure that TB research reflects community priorities. DESCRIPTION Since 2014, the TB CAB and CRAG have reviewed protocols for 13 late-stage TB clinical trials from for- and non-profit product developers, public research networks, and academic investigators. We conducted a qualitative review of the feedback provided to evaluate our experiences and identify frequently encountered issues of concern. CONCLUSIONS Areas repeatedly overlooked in TB protocols point to a need for continued dialogue between researchers and CABs. While some global and site-specific community engagement programs exist, there is an urgent need to ensure that all TB trials engage communities in protocol development so that research better reflects their needs and priorities. Toward this end, researchers should consider adding a CAB representative to the protocol team or trial steering group; making time for site-level CABs to review and provide feedback on the protocol and other study materials; and scheduling CAB check-ins at different stages of the protocol development process. Researchers and community groups should work together to develop best practices for community participation in protocol development. SUMMARY OF REVIEWED TRIALS PROTOCOLS TRIAL DESCRIPTION TBTC S35 To evaluate the pharmacokinetics and safety of 3 months of once-weekly rifapentine and isoniazid (3HP) in children with latent TB infection TBTC S31 To evaluate whether rifapentine +/- moxifloxacin can shorten treatment for drug-sensitive TB to 4 months TRUNCATE TB To evaluate whether combinations of existing, new, and repurposed drugs can shorten treatment for drug-sensitive TB to 2 months STAND To evaluate whether pretomanid, moxifloxacin, and pyrazinamide can shorten treatment for drug-sensitive TB to 4 months *includes exploratory arm for multidrug-resistant TB CLAM320B2202 To evaluate the efficacy and safety of clofazimine when given with an optimized background regimen for 18–24 months for multidrug-resistant TB C211 To evaluate the pharmacokinetics and safety of bedaquiline in children A5343 To identify drug-drug interactions and evaluate the safety of concomitant treatment with bedaquiline and delamanid PRACTECAL To evaluate whether combinations of pretomanid, bedaquiline, moxifloxacin, linezolid, and clofazimine can shorten treatment for multidrug-resistant TB to 6 months NExT To evaluate whether a bedaquiline-containing, injectable-free regimen can shorten treatment for multidrug-resistant TB to 6 months endTB To evaluate whether bedaquiline- and delamanid-containing, injectable-free regimens can shorten treatment for multidrug-resistant TB to 9 months STREAM II To evaluate whether bedaquiline-containing regimens can shorten treatment for multidrug-resistant TB to 6 months or replace the injectable in a 9 month regimen Nix-TB To evaluate whether pretomanid, bedaquiline, linezolid can shorten treatment for extensively drug-resistant TB to 6–9 months New Start To evaluate a pragmatic 18 month bedaquiline-containing, all oral regimen for drug-resistant TB COMING SOON: PROTOCOL REVIEW TOOLKIT FOR ACTIVISTS The CRAG is an international, community-based advisory body that works to ensure the meaningful participation and engagement of affected communities in research conducted by the U.S. Centers for Disease Control and Prevention’s Tuberculosis Trials Consortium (TBTC). The TB CAB is a group of strong, research literate community activists who act in an advisory capacity for product developers and institutions conducting clinical trials of new TB drugs, regimens, diagnostics, and vaccines; and provide input on study design, early access, regulatory approval, post marketing, and implementation strategies. Protocol Review Companion   Refer to the questions in this document as you read protocols to guide your review of different aspects of the proposed study. Use it as a checklist or thinking aid.    Stimulate your thinking Protocol Input Questionnaire   Fill this out to provide feedback to researchers on the protocol. Note any concerns or aspects of the study that you would like to see changed. Organize your feedback Trial Rating Rubric    Use this to keep track of any changes made to the protocol based on your review and feedback. CABs can use this internally to measure and evaluate the impact of their work.   Evaluate your impact Lindsay McKenna Global TB CAB Coordinator Lindsay.McKenna@treatmentactiongroup.org Mike Frick CRAG Coordinator Mike.Frick@treatmentactiongroup.org Wim Vandevelde Global TB CAB Chair Wim@eatg.org Dorothy Namutamba CRAG Chair dnamutamba@icwea.org Visit the TB CAB online at tbonline.info Visit the CRAG online at http://crag-tb.tumblr.com PRESENTED AT THE 21ST INTERNATIONAL AIDS CONFERENCE - DURBAN, SOUTH AFRICA