Goal 3: Advance Translational Research

Tools to facilitate availability and safe use of innovative blood products and their analogs

Novel blood products are being developed based on innovative science (e.g., ex vivo manufactured RBC and platelets, and platelet and plasma derived hemostatic products). However, there is a significant lag in the development of appropriate tools and model systems, which poses a challenge when evaluating such products for regulatory approval.

Submitted by (@chintamani.atreya)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

The rapid advancement in science and technology has identified pathways for ex vivo manufacturing of RBC and platelets; platelet and plasma derived hemostatic products and recombinant coagulation factors, etc. However, these novel products have to be evaluated for their safety, efficacy, purity and potency as part of regulatory approval process. Because the new products are manufactured using innovative technologies some of the existing tools for their evaluation are inadequate. Therefore, future investments in the development of necessary predictive tools (I.e. regulatory science tools) in areas such as the following will positively impact the availability and safe use of innovative blood products and their analogs: 1) the development of analytical and biochemical assays, 2) animal models for product safety and efficacy, 3) product quality-associated biomarkers to characterize storage lesions of RBC and platelets and 4) functional assays and molecular and bioinformatics models that can predict the success of novel blood products both during manufacturing and with respect to clinical patient outcomes.

Feasibility and challenges of addressing this CQ or CC :

This initiative is feasible as investigators in blood organizations, academia and government are already working independently towards this goal in their defined areas of study. However, a coordinated effort among these independent entities could help in the faster development of necessary regulatory science tools to optimize care of individual patients and patient groups.

Name of idea submitter and other team members who worked on this idea : Office of Blood Research and Review, CBER, FDA

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17 up votes
5 down votes
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Goal 2: Reduce Human Disease

Goal-directed versus Fixed-ratio plasma resuscitation in surgical (non-trauma) hemorrhage

For surgical patients meeting criteria for the critical RBC administration threshold (CAT) due to an associated coagulation disorder, which hemostatic resuscitation strategy (goal-directed versus ratio-based) is superior?

Submitted by (@darylkor)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Perioperative hemorrhage remains a significant concern. Coagulopathy frequently develops in the setting of surgical hemorrhage and the optimal strategy for addressing this issue remains a matter of debate.

Military experience suggests the application of ratio-based plasma transfusion practices may improve clinical outcomes in the setting of massive hemorrhage. However, numerous concerns (e.g. survival bias, uniqueness of a military population, risk for adverse events related to high-volume plasma transfusion) preclude the broad generalization of such strategies to non-trauma surgical populations.

Goal-directed hemostatic resuscitation strategies (e.g. coagulation management based upon the results of hemostasis testing) have shown promise in specific surgical environments such as cardiac surgery and liver transplantation. However, definitive direct comparisons between goal-directed strategies and alternative approaches such as fixed-ratio plasma transfusion have not been performed. Moreover, the role of such strategies in more heterogeneous surgical populations remains uncertain. To better define the optimal approach to plasma transfusion strategies in the setting of intraoperative (non-trauma) hemorrhage, we propose a multicenter clinical trial directly comparing fixed-ratio and goal-directed plasma resuscitation strategies in the operating room environment.

Feasibility and challenges of addressing this CQ or CC :

Surgical patients with increased risk of hemorrhage may be targeted to improve subject recruitment (e.g. cardiac surgery, liver transplantation, aortic vascular surgery, multi-level instrumented spinal fusions or tumor resections, etc). Therefore, an adequately sized study population is likely to be present in a multicenter study and we believe such a trial would be feasible with NHLBI support.

 

To further enhance the feasibility of identifying a surgical population experiencing significant hemorrhage in a time-efficient manner, predictive algorithms such as the critical RBC administration threshold (CAT) could be also be employed.

 

The optimization of decisions related to plasma transfusion has the potential to improve not only clinical outcomes, but also healthcare resource utilization. Therefore, the outcomes of a trial in this domain could include both patient-important outcomes (e.g. mortality, bleeding complications), as well as outcomes related to healthcare utilization (e.g. total blood products consumed, hospital length of stay).

Name of idea submitter and other team members who worked on this idea : Daryl J. Kor, MD and Walter H. Dzik, MD for the 2015 NHLBI State of the Science in Transfusion Medicine.

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11 net votes
30 up votes
19 down votes
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Goal 3: Advance Translational Research

Overcoming barriers to translational regenerative medicine

Current stem cell based approaches to translational medicine predominantly show modest efficacy. Most research rest on accepting existing limitations and focusing upon "tweaks" to the experimental model rather than taking on important barriers head on. The efficacy of stem cell-based regenerative medicine will never be fully realized unless we stop trying overly simplistic approaches such as"more is better" and start ...more »

Submitted by (@heartman4ever)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

The field of regenerative medicine holds great potential but we risk losing the public trust by hyperbolic promises, modest efficacy, and incremental research steps. Truly innovative research will transform the landscape and offer truly novel therapeutic approaches to many current incurable conditions. The result is a dramatic shift in the practice of medicine, new options for treatment, enhanced engagement of the public in biomedical research and new growth opportunities for the NIH and biotech sectors.

Feasibility and challenges of addressing this CQ or CC :

The future is here for regenerative medicine, but for the most part the potential and practice has been unrealized or poorly executed. The challenge is to identify the limiting factors and sweep them aside. There is broad and surprisingly consistent consensus on what the barriers are to successful regenerative therapy, but it seems most researchers are complacent and accept these limitations as inherent in the system rather than try to find truly combative approaches to overcome the barriers to enhancing regenerative processes. So it is essential to change the current mindset and push for a full frontal attack on the barriers that impede successful regeneration rather than minor modifications or uninspired brute force approaches that ignore the underlying mechanistic issues. Also, a major challenge is the hyperbole and overselling of research findings and impact by researchers and their institutions looking to capitalize upon the "discovery de jour." Such overly optimistic and unrealistic promises undermine our position in the public eye and compromise our future ability to earn the public trust.

Name of idea submitter and other team members who worked on this idea : M Sussman

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-6 net votes
14 up votes
20 down votes
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Goal 2: Reduce Human Disease

Phase III efficacy trials of tuberculosis drugs

1) Phase III efficacy trials of new tuberculosis drugs (e.g., bedaquiline, delamanid, PA-824) that have shown promise in early phase studies for multidrug-resistant tuberculosis. 2) Phase III efficacy trials of new and existing tuberculosis drugs to development very short course regimens (3-4 months). 3) Phase III efficacy trials of new and existing drugs for treatment of latent tuberculosis infection in contacts of ...more »

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Name of idea submitter and other team members who worked on this idea : American Thoracic Society member

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1 net vote
1 up votes
0 down votes
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