Sickle Cell Disease Advisory Committee Minutes

Video conference


Welcome and General Introductions

On behalf of Dr. Julie Panepinto, Director for the Division of Blood Diseases and Resources (DBDR), Dr. Traci Mondoro, Chief of the Translational Blood Diseases and Resources Branch, opened the meeting by introducing the Sickle Cell Diseases Advisory Committee (SCDAC) members and NHLBI speakers. Dr. Mondoro emphasized the need to change the structure of future SCDAC meeting by having more dialogue between members and engaging in a two-way conversation, rather than one-sided presentations for a more effective meeting. She also mentioned the possibility of returning to in-person meetings (possibly a hybrid model) to facilitate more engaging discussions, all of which was well received by committee members.

NHLBI SCD program updates

Dr. Andrei Kindzelski presented NHLBI clinical trial mechanisms while Dr. Traci Mondoro presented an overview of SCD programs, including updates on the portfolio. During the discussion, members expressed appreciation for time added to the agenda to allow for discussion and feedback. Recommendations for next year’s SCDAC meeting included for NHLBI to discuss different funding opportunities, incorporate specific funding mechanisms, present data analyses on NIH funding in SCD, and discuss the imbalance in the field of hematology, the latter due in part to the limited number of experts in the field available to participate on review panels. NHLBI agreed with the recommendations and encouraged colleagues in hematology to mentor young investigators and urge them to serve on review panels. In terms of applying to the various grant mechanisms, NHLBI highly recommends to first speak with a program officer to learn more on the procedure and process of applying. Second, every institute and center (IC) has their own strategy to support a clinical trial and as a result there are a number of mechanisms available to choose from. It is important for investigators to carefully review the criteria and reach out to the different ICs to help strengthen and increase the chances for a more successful application.

The committee members had discussions that centered on several other key points that included: the importance of NHLBI leadership to support SCD research and portfolio analyses for examining SCD funding and investment over time, and how to best support the infrastructure needed to conduct clinical trials.

NHLBI staff presented NHLBI initiatives and collaborations such as the NHLBI SickleInAfrica program, BloodSafe program; the Recipient Epidemiology and Donor Evaluation Study (REDS) program, and the Cure Sickle Cell initiative (CureSCI), which includes two ongoing gene therapy clinical trials and is accruing successfully. CureSCI also includes the following: the Natural History Data Resource, the Clinical and Economic Impact (CEIA) analysis group, the Community Input Panel, and work with the California Institute for Regenerative Medicine (CIRM). Members of the committee recommend for the CureSCi to include work to better understand existing scientific gaps in SCD, how to address them and involve the community in this work.

Committee members recommended for NHLBI to build a stronger collaboration with the ASH Clinical Research Hub better understand community needs when prioritizing future work; collaboration with the Gates Foundation whose current emphasis is on HIV; and finally, a closer collaboration with other ICs. Such as the Center for Translation Research and implementation Science (CTRIS), as well as the National Institute of Child Health and Human Development (NICHD), for potential co-funding of clinical trials with the Blood Division.

Leveraging Networks to Conduct Successful Clinical Trials in Sickle Cell Disease 

Dr. Kindzelski presented on the Strategies to Innovate Emergency Care Clinical Network (SIREN) and on Pediatric Emergency Care Applied Research Network (PECARN). He explained that SIREN is dynamic and has well-developed clinical trial methodology center which offers regular webinars and courses for investigators both within and outside the network. An interesting aspect of SIREN is that its mission also includes SCD and is not limited to trauma. However, to be part of the SIREN umbrella, projects must undergo a specific evaluation involving the joint communication between SIREN and NHLBI. The second network Dr. Kindzelski discussed was PECARN, a federally funded network which features seven research node center centers across the country and serves approximately one million children per year. Although PECARN has a complex structure, it is easy to get in touch with them. However, in order to do clinical research using PECARN infrastructure or utilize PECARN resources such as their research data sets, the applicant must have funding for the research that is being proposed (for example federal funding).

Dr. Traci Mondoro presented on NICHD networks in the absence of the NICHD speaker, who was unable to join the meeting. Dr. Mondoro explained that although NICHD has a small budget, they fund infrastructure and have networks that support clinical trials that can be leveraged by investigators and consortia, so that NHLBI does not need to recreate clinical trial networks. The networks discussed were: the Neonatal Research Network, which is comprised of 18 centers, focuses on transfusion, but it is not necessarily related to SCD; the Maternal-Fetal Medicine Network, which consists of more than 10 centers and has an open Request for Information (RFI) for pregnant women with SCD; the Psychiatric Intensive Care Unit (PIC-U) Network, and the Collaborative Pediatric Critical Care Research Network (CPCCRN), which are other smaller, but significant networks that facilitate work with animal models and therapeutics. More information will be obtained from NICHD and shared with the SCDAC members. In addition, NINDS leads the Common Fund’s Helping to End Addiction Long-term (HEAL) initiative that has specific SCD funding opportunities and also multiple pain focused initiative that can leveraged for pain focused funding.

Dr. Nancy DiFronzo presented on the Bone Marrow Transplant Clinical Trials Network (BMT CTN) which was established in 2001 by NHLBI. It supports 20 transplant centers or consortia along with one data coordinating center (DCC). Dr. DiFronzo explained that the BMT CTN steering committee oversees governance, reviews every trial concept coming their way, deciding which ones to pursue. All their meetings are open, which means investigators from core of affiliate centers can participate. Also, the BMT CTN can explore partnerships with industry; however, these partnerships require interactions with NHLBI & the DCC, as well as budget development to provide necessary support for studies. This network uses the Center for International Blood and Marrow Transplantation Research (CIBMTR) for data collection and evolves over time based on requirements. All data from BMT CTN must be posted in the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC).

General Discussion & Committee Recommendations 

The last segment of the meeting was open for a general discussion, and for additional committee recommendations, which are listed below:

  1. Established infrastructure for clinical trial networks with more focus on classical hematology to elevate scientific impact and develop better and less expensive trials leading to more affordable therapies. The model of Pragmatic Clinical Trials can leverage Electronic Health Records (EHRs) for more efficient trial management.
  2. Creation of a specialized sickle cell study section to boost funding opportunities specific to SCD, and a strategy to route grants through such study sections that have an understanding of SCD.
  3. Establish and follow-up cohorts from pediatrics to adults to understand which patients will develop end-organ failure, late stroke, or other SCD complications.
  4. Foster advocacy within the NIH for resources to target patients with SCD and advocate for research in the SCD field.
  5. Foster community-based participatory research, which should include a Community Advisory Board for each clinical trial site, and a central version, bringing lived experiences to the table.
  6. Support gene therapy research with an implementation focus to reduce the time window for the development of new interventions.
  7. Invest in disparities and implementation research.
  8. Include international representatives in the SCDAC to increase innovation in sickle cell research globally as well as to obtain current updates from global advances in SCD research. Response from NHLBI: Per the SCDAC Charter, members have to be US citizens or have green card/permanent resident card.
  9. Develop notices of funding opportunities (NOFOs) to advance research related to pregnancy, and aging in SCD because those topics are currently understudied. 
  10. Increase resources for mental health interventions for patients with SCD.

Marsha J. Treadwell, PHD
Julie A. Panepinto, MD, MSPH