Translational Science Benefits
Summary
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and highly curable in high-income settings like the United States and Europe. However, in low- and middle-income countries (LMIC) most children diagnosed with this form of cancer are less likely to survive. Many factors contribute to this gap in survival. One critical factor is limited access to emerging treatments, such as immunotherapies. Immunotherapies use your body’s own immune system to kill cancer cells which, compared to traditional chemotherapy, causes fewer side effects and is more effective at treating the cancer. Blinatumomab (Blincyto®) is an evidence-based immunotherapy first approved by the U.S. Food and Drug Administration in 2014. Widespread use of blinatumomab outside of high-income settings is limited due to high cost, limited commercial availability, and complex implementation challenges. As a result, there is very little evidence for how this drug works for children in the real world.
The Blincyto® Humanitarian Access Program (BHAP) is a unique collaborative effort between St. Jude Children’s Research Hospital, the pharmaceutical industry, and a non-governmental organization to provide blinatumomab to children in LMIC where the drug is not available for purchase. Implementing NOVel Agents and Translating Innovation Globally (INOVATING) is a research study that runs in parallel to this drug donation program and examines how blinatumomab is integrated into local health systems. The study is administered by local teams and ultimately addresses and evaluates how well the drug works for patients in LMIC. The goals of this study were to develop a roadmap that can be used to support other teams implementing blinatumomab or similar types of emerging complex immunotherapies in LMIC centers.
Immunotherapies like blinatumomab have unique administration requirements and side effect profiles that differ from most other chemotherapies. Previous guidelines for delivering this medicine and providing supportive care were based off of experience in high resource settings. Therefore, one of the goals of this study was to support healthcare providers in lower resource settings by enhancing their clinical knowledge and confidence delivering immunotherapy. To prepare local doctors, nurses, and pharmacists, the study team developed a training toolkit and modified guidelines for blinatumomab preparation, administration, and side effect management based on the resources available to them (Figure 1). Also, the program created a Medical Expert Panel to work with local teams and answer questions about administering the medicine or managing side effects.
Significance
For complex and expensive cancer treatments like blinatumomab, experience from high-income countries is not sufficient to inform clinical practice in lower resource areas. This study partnered with healthcare providers working at hospitals in LMIC who care for kids with cancer that otherwise would not have access to blinatumomab. These teams worked together to identify what local resources would impact how blinatumomab could be given and how to safely manage patients receiving the treatment at their center. Importantly, this program shows that complex and costly cancer treatments like blinatumomab can be successfully administered outside of high-income settings with the support of innovative partnerships and resource adapted guidance. This approach models how unique partnerships, expanded access, and thoughtful implementation of evidence-based cancer treatments can be leveraged to benefit patients in LMIC, who make up 80% of pediatric cancer diagnoses worldwide.
Ultimately, this initiative has the potential to contribute valuable real-world knowledge that could help shape future policy decisions. By better understanding the effectiveness and accessibility of emerging cancer treatments, the initiative aims to support efforts in expanding global access to these life-saving drugs, ensuring they reach those who need them most. In doing so, it may play a key role in addressing disparities in cancer care and improving health outcomes on a broader scale.
Benefits
Demonstrated benefits are those that have been observed and are verifiable.
Potential benefits are those logically expected with moderate to high confidence.
Helped improve global drug access by establishing a method for academic communities and global agencies to engage meaningfully and productively with the pharmaceutical industry. demonstrated.
Clinical
Improved access to educational resources and tools to guide safe drug delivery by creating a customized training toolkit for medical teams. demonstrated.
Clinical
Improved the safe and effective treatment of patients by establishing a feasible standard of care to safely administer the drug outside of traditional, high-resourced settings and creating guidelines for medical teams based on available local resources. demonstrated.
Clinical
Created customized procedures standardized for hospitals in limited resource settings to prepare and administer the drug and care for patients receiving the complex cancer therapy. Provided ongoing consultation and guidance about clinical care and hospital-specific procedures. demonstrated.
Clinical
Improved timeliness and quality of care by modeling communication and collaboration needed between members of the medical team to build mutual trust and support safe delivery of complex cancer treatment. demonstrated.
Clinical
Created opportunity for institutions to demonstrate their clinical competency with complex therapies. As a result of this collaboration, these institutions, which historically did not have relationship with the pharmaceutical industry are now being considered in the next generation of clinical trials for advanced cancer therapy. potential.
Clinical
Provided an opportunity for free access to a high-cost drug in countries where it is not commercially available, and improved timely and equitable access to emerging and effective treatments. demonstrated.
Community
Increased access to complex cancer drugs in limited resource settings by establishing a new process that supports medical teams with the knowledge and skills necessary to deliver treatment. demonstrated.
Community
Expanded treatment options, enhanced effectiveness of that treatment, and increased survival for patients with hard-to-treat leukemia by providing access to a drug that is less toxic than traditional chemotherapies. demonstrated.
Community
Created a cost-effective and comprehensive training program to enhance provider comfort, skillset and knowledge, and prepare different members of the medical team to deliver this complex therapy. demonstrated.
Community
Developed local expertise for delivering complex cancer medicines in limited resource settings and built a network of healthcare providers, potentially creating opportunity for future collaborations to address local inequities as new therapies emerge. potential.
Community
Created potential to increase global access to training materials for healthcare teams for blinatumomab and other complex therapies by establishing an effective process for resource development and team preparation. potential.
Community
Enhanced diversity, equity, creativity, and sensitivity in healthcare services by building multi-language, multi-cultural, and multi-national expertise in emerging complex cancer drugs. demonstrated.
Economic
Potentially reduce serious chemotherapy side effects and costly hospital care for cancer patients in LMIC by improving access to blinatumomab. potential.
Economic
Shared this work and findings as poster presentations and invited talks at multiple international conferences. demonstrated.
Policy
May improve evidence-based policy around complex cancer treatments in diverse global settings by publishing findings in international scientific journals. potential.
Policy
Provided evidence that blinatumomab can be effectively administered in LMIC, thus strengthening the evidence base for future data-driven policies aimed at expanding global drug access. potential.
Policy
This research has clinical, community, economic, and policy implications. The framework for these implications was derived from the Translational Science Benefits Model created by the Institute of Clinical & Translational Sciences at Washington University in St. Louis.
Clinical
The unfortunate reality is that many new and emerging cancer drugs are not available across the globe. Previous attempts to improve access to these treatments did not have the necessary clinical support to adapt them for global settings. Over the last twenty years, more and more immunotherapies have become standard treatments for pediatric cancers, increasing the need to improve access and prepare teams to administer these complex treatments. We addressed access through a novel collaboration model, created the appropriate guidelines for a new standard to manage patients in limited resource settings, and designed a training program to prepare all the members of the healthcare team.
Increasing the providers’ knowledge and comfort with this new treatment helped improve safe administration and minimize side effects and complications. This study also demonstrated that with this collaborative approach, complex therapies could be administered in lower-resource settings in a way that was doable and fit into the existing health systems at these centers. Additionally, it showed that the approach provided clinical benefit of blinatumomab for local patients. Providing access to this new category of treatment with lower side effects was an additional contributor to improved survival.
Additionally, this work created a process to expand access beyond what is being done in the blinatumomab drug donation program which could be applied to other emerging types of treatments in the future.
Long-term outcomes such as those identified by this research are critical to inform future local practice and may represent an opportunity for bidirectional learning in healthcare systems.
Community
This project increased access to blinatumomab for multiple healthcare institutions in LMIC and to guidelines and trainings for multidisciplinary care providers on how to prepare, administer and manage patients receiving this complex immunotherapy. As a result, this work helped build networks of expertise in regions where they previously did not exist. Additionally, the study’s global collaboration between hospitals, a non-governmental organization, and the pharmaceutical industry deepened partnerships, which ultimately has the potential to improve long-term community health.
Economic
Even with these new cancer drugs, the cost of care extends beyond the cost of the drug itself. This study helped identify real-world costs associated with safely administering complex therapies in LMIC and provided evidence that alternative advanced treatments may be able to replace other high-cost interventions and relieve the financial burden on patients and families. It also created and used cost-effective strategies, such as virtual trainings and free online educational resources, to prepare medical teams and reduce preventable complications.
This work made the most of the drug donation program, ensuring that the pharmaceutical company’s investment and drugs were used appropriately and for the best benefit of patients.
Policy
For complex cancer treatments such as blinatumomab for pediatric patients, high-income country experience is not sufficient to inform real-world implementation. This research identified strategies to demonstrate not only how to successfully implement complex therapies in existing health systems in limited resource settings across the world but also showed that as a result of successful implementation, this treatment benefits patients in these regions. The evidence generated by this study has the potential to support policy change globally.
Lessons Learned
This study demonstrated the value of using implementation methodology to translate emerging, complex cancer treatments globally in countries with no commercial access. This effort was a unique combination of fostering collaborations, developing a new standard approach to care delivery in a limited resource setting, and systematically studying the real-world implementation of blinatumomab. This created generalizable knowledge and scalable solutions for safe and effective delivery of this complex cancer therapy globally. Designing and providing cost-effective educational tools, trainings and other resources to medical teams, supporting their internal collaboration and increasing their comfort with blinatumomab administration helped strengthen the participating hospitals’ healthcare systems. As a result, this approach expands impacts of emerging treatment equity of benefits beyond high-income settings.
Challenges in collecting clinical data in limited resource settings persisted (it was harder to get the data than implement the drug), but the study was able to collect sufficient real-world evidence to show that safe and successful implementation of blinatumomab is possible in these regions. These research findings will support sustainability efforts for emerging, novel therapies often associated with a high cost and lead to opportunities for cost savings, increase drug access, policy change and long-term collaborative efforts to improve childhood cancer survival globally.
- Luke DA, Sarli CC, Suiter AM, et al. The Translational Science Benefits Model: A New Framework for Assessing the Health and Societal Benefits of Clinical and Translational Sciences. Clin Transl Sci. 2018;11(1):77-84.
- Duffy, C., Santana, V., Inaba, H. et al. Evaluating blinatumomab implementation in low- and middle-income countries: a study protocol. Implement Sci Commun 3, 62 (2022). https://doi.org/10.1186/s43058-022-00310-5