Showing 6 ideas for tag "safety"

Goal 2: Reduce Human Disease

The potency and safety of transfusable red blood cells

Can we identify approaches to improve potency and/or safety of transfusable RBCs?

42 day pre-transfusion storage of RBCs maximizes utilization, while minimizing waste. However, RBCs undergo changes during collection, manipulation and storage that may reduce their potency or safety. Progress in understanding markers that predict transfusion success at the time of collection and with storage remains slow. New technologies... more »

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

Details on the impact of addressing this CQ or CC

While novel RBC storage methods have been described, the mechanisms underlying their efficacy has not been defined, a step that will be important for further improvements in this area. Some of these methods appear to improve efficacy of the RBC bioenergetic pathways; however, to date there have not been notable advances in reducing cytoskeletal defects common in stored RBCs. The development of new RBC preservation methods that minimize the impact of the storage lesion on specific areas of concern (e.g., diminished oxidation/peroxidation, decreased membrane fragility) is needed.

 

Use of ex vivo generated RBCs is an alternative to conventional donor-derived RBCs which can potentially improve product consistency, reduce the storage lesion, and improve safety. However, advances are needed before this approach is feasible on a large scale. While the development of blood substitutes including blood pharming will likely require more than 3-10 years before it can be ready for the clinic, Blood Pharming from hematopoietic stem/progenitor cells is now technically feasible and the recent development of genome editing methods suggests the exciting possibility of generating GMP compliant “immortal” stem cell sources to produce transfusable RBCs.

Feasibility and challenges of addressing this CQ or CC

Research should include both pre-clinical and clinical studies to define optimal combinations of known factors preserving red cells (e.g. hypo-osmolarity, energy sources, antioxidants), and the development of methods for RBC pathogen reduction that do not increase the storage lesion.

Procedures for generating blood cells from cultured stem/progenitor cells is not currently cost-effective, limiting near term applications to special patient populations such as specific RBC phenotyping of rare donors for chronically transfused patients. Areas of research needed to advance the development of blood substitutes and blood pharming include: (a) new approaches to blood substitutes including artificial oxygen carriers generated from red cell lysates/components or engineered from combinatorial chemico-biological approaches (e.g., derivatization of hemoglobin, encapsidation of modulated oxygen carriers); (b) a better understanding of the biological properties of cultured RBCs with the goal of reducing blood pharming costs; (c) optimizing methods to expand stem cell populations while allowing differentiation to selected clinically relevant blood cell populations at clinically relevant levels; and (d) optimizing methodologies that faithfully replicate embryonic development to develop the cells of interest.

Name of idea submitter and other team members who worked on this idea Nareg Roubinian, MD and Naomi Luban, MD for the NHLBI State of the Science in Transfusion Medicine

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31 up votes
17 down votes
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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.

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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12 net votes
17 up votes
5 down votes
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Goal 3: Advance Translational Research

Implementation Research to Improve Global Availability of Safe Blood Transfusions

What well-developed principles and lessons learned can be employed to improve the safety and availability of blood transfusions in developing countries?

The WHO Global Status Report 2013, many research reports, and a recent assessment of burdens of transfusion transmissible infections with HIV, HBV and HCV identified several critical challenges: 1) Significant proportions of blood collections in a large number of countries... more »

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

Details on the impact of addressing this CQ or CC

Significant progress has been made globally in providing adequate supply of safe blood for clinical transfusion thanks to efforts by many, including the US PEPFAR and research supported by NIH such as the REDS programs. Nevertheless, there remains a lack of blood for transfusion and paid blood donations are still collected in many countries. A total of 25 countries were not able to screen all donated blood for one or more of infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis in 2011. As many as 24% of blood donations in low-income countries were not screened following basic quality procedures which include documented standard operating procedures and participation in an external quality assurance scheme. (WHO: Global Status Report 2013). Implementation research to identify cost-effective and sustainable ways to improve blood supplies in the developing world can help reduce blood shortage while enhancing safety by eliminating transfusion transmission of HIV, HBV and HCV.

Feasibility and challenges of addressing this CQ or CC

Research, including studies supported by the NHLBI REDS, REDS-II, and REDS-III programs, has identified major gaps in global blood supply and reasons for such gaps. International programs, especially PEPFAR, have gained valuable experience implementing quality systems. The time has come to conduct research to optimize the implementation, that is, to find out how to improve global supply of safe blood for transfusion more efficiently in local settings and in a more sustainable manner.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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7 net votes
20 up votes
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Goal 2: Reduce Human Disease

Predict the needs for inter and intra-hospital transfer for acute care surgery patients with respiratory failure

Density mapping of the need and flow of patients requiring acute care surgery vis-a-vis inter-facility transfer, care hand-off failures, post-acute care resource mismatch to articulate a funding plan resource allocation and development akin to what has been done for trauma care.

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 Society of Critical Care Medicine Executive Committee/Council

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2 down votes
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Goal 3: Advance Translational Research

Improving Drug Safety through Precompetitive Research

The lack of transparency in Pharma clinical studies and the incomplete knowledge of the effect of genetic profiles and pharmacological factors on drug toxicities are challenges in decreasing drug development costs and increasing drug safety.

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

Details on the impact of addressing this CQ or CC

Precompetitive research and collaborations directed at improving our understanding of the factors underlying adverse patient responses to investigational heart, lung, blood, sleep drugs will help to expedite the drug development process, increase probabilities of success and reduce product development costs.

Feasibility and challenges of addressing this CQ or CC

Several public-private initiatives such as The Predictive Safety Testing Consortium and the Cardiac Safety Research Consortium are underway that address components of this problem. NHLBI can join existing initiatives or formulate its own. In either case, NHLBI’s participation as either an honest broker or a funding source will enable substantive progress on several fronts over a 5-10 year period.
Clinical safety complications and chronic exposure toxicities are a major cause of drug trial failures and recalls and thereby contribute to the high cost of pharmaceutical product development and the rising prices of commercial medicines. Safety problems can usually be attributed to the off-target biological effects of drug compounds or their metabolites. Reducing the safety risks associated with drug development will therefore require us to expand our knowledge around the pharmacological and pharmacogenomic factors underlying adverse safety events. Furthermore, adverse events that occur during clinical studies that are conducted by pharmaceutical companies are not usually shared publicly. This lack of transparency contributes to unnecessary inefficiencies and costs in the drug development process.
Mechanisms for minimizing safety hurdles in drug development include funding precompetitive applied research and promoting collaborations among companies to encourage sharing of clinical failure data.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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13 up votes
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Goal 3: Advance Translational Research

Leverage Information Technology to Improve Patient Safety in Surgery

Progress toward a six-sigma level of safety (already achieved in commercial aviation) has been slow in medicine and surgery. The best cardiac surgery program operates at only 3.5 sigma level. In order to acceletate this process, it is critical to leveage recent advances in information technology, including but not limited to natural language processing (NLP), advanced speech recognition, artificial intelligence.

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

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