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1.
Transplant Cell Ther ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38762057

RESUMO

Genetically modified cell therapies (GMCT), particularly immune effector cells (IEC) such as chimeric receptor antigen (CAR) T cells, have shown promise in curing cancer and rare diseases after a single treatment course. Following close behind CAR T approvals are GMCT based on hematopoietic stem cells, such as products developed for hemoglobinopathies and other disorders. Academically sponsored GMCT products, often developed in academic centers without industry involvement, face challenges in sustaining access after completion of early phase studies when there is no commercial partner invested in completing registration trials for marketing applications. The American Society for Transplantation and Cellular Therapy (ASTCT) formed a task force named ACT To Sustain (Adoptive Cell Therapy to Sustain) to address the "valley of death" of academic GMCT products. This paper presents the task force's findings and considerations regarding financial sustainability of academically sponsored GMCT products in the absence of commercial development. We outline case scenarios illustrating barriers to maintaining access to promising GMCT developed by academic centers. The paper also delves into the current state of GMCT development, commercialization, and reimbursement, citing examples of abandoned products, cost estimates associated with GMCT manufacturing and real-world use of cost recovery. We propose potential solutions to address the financial, regulatory, and logistical challenges associated with sustaining access to academically sponsored GMCT products and to ensure that products with promising results do not languish in a "valley of death" due to financial or implementational barriers. The suggestions include aligning US Food and Drug Administration (FDA) designations with benefit coverage, allowing for cost recovery of certain products as a covered benefit, and engaging with regulators and policy makers to discuss alternative pathways for academic centers to provide access. We stress the importance of sustainable access to GMCT and call for collaborative efforts to develop regulatory pathways that support access to academically sponsored GMCT products.

2.
Hum Gene Ther ; 34(23-24): 1180-1189, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37964764

RESUMO

Little is known about patients' and families' lived experiences of participating in pediatric gene therapy (GT) clinical trials. Currently, pediatric GT research targets a broad range of indications--including rare and ultra-rare diseases--which vary in severity and in the availability of alternative therapies. Pediatric GT differs meaningfully from adult GT because the decision to participate involves a dyad of both the child and parent or caregiver/s. It is critical to understand patients' and caregivers' perceptions and experiences of social, emotional, physical, and logistical burdens or benefits of participating in such trials, and how they weigh and prioritize these factors when deciding whether to participate. We conducted a scoping review of the current literature in this subject area with objectives to (1) provide an overview of existing literature, (2) identify gaps and areas for further research, and (3) better understand the lived impact of pediatric GT research on patients and their parents/caregivers. Four themes emerged, including (1) weighing risks and benefits (2) timing of GT trial participation, (3) value of clear communication, and (4) potential impact on quality of life. Notably, our sample surfaced articles about how patients/parents/caregivers were thinking about GT-their understanding of its safety, efficacy, and risks-rather than accounts of their experiences, which was our initial intention. Nevertheless, our findings offer useful insights to improve the informed consent process and promote a more patient- and family-centered approach. Moreover, our findings can contribute to patient advocacy organizations' efforts to develop educational materials tailored to patients' and families' expressed informational needs and perspectives, and can inform more patient- and family-centered policies from GT clinical trial sponsors.


Assuntos
Terapia Genética , Pais , Adulto , Criança , Humanos , Cuidadores/psicologia , Pais/psicologia , Ensaios Clínicos como Assunto
3.
Innov Clin Neurosci ; 20(1-3): 18-24, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122578

RESUMO

This article expands upon a session, titled "Implications of Pediatric Initiatives on CNS Drug Development for All Ages-2020 and Beyond," that was presented as part of a two-day meeting on pediatric drug development at the International Society for Central Nervous System (CNS) Clinical Trials and Methodology (ISCTM) Autumn Conference in Boston, Massachusetts, in October 2020. Speakers from various areas of pediatric drug development addressed a variety of implications of including children in drug development programs. The speakers wrote summaries of their talks, which are included here. The session's lead chair was Dr. Gahan Pandina, who wrote introductory and closing comments. Dr. Joseph Horrigan addressed the current landscape of pediatric development programs. Dr. Gahan Pandina addressed how the approach to research in pediatric populations affects the drug development process and vice versa. Dr. Alison Bateman-House discussed the ethical implications of research in the pediatric population. Dr. Luca Pani discussed some of the global regulatory issues and challenges concerning research in pediatric patients. Dr. Judith Kando served as a discussant and posed new questions about means of facilitating pediatric research. Finally, Dr. Gahan Pandina provided closing comments and tied together the presented issues. This paper should serve as an expert-informed reference to those interested and involved in CNS drug development programs that are aimed at children and/or required, through regulations, to include children as part of the approval process.

4.
JAMA Netw Open ; 6(2): e230060, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36800184

RESUMO

This qualitative study explores academic oncologists' needs and satisfaction with expanded patient access to investigational drugs.


Assuntos
Drogas em Investigação , Oncologistas , Humanos , Drogas em Investigação/uso terapêutico , Ensaios de Uso Compassivo
5.
Pharmaceut Med ; 37(1): 17-24, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36527677

RESUMO

Currently, pediatric research involving investigational gene therapies (GT, used without intending to imply a therapeutic effect) targets a broad range of indications (including rare and ultra-rare diseases) that vary in severity and availability of approved disease-modifying therapies. Because of this diversity of circumstances, there is no one-size-fits-all list of ethical concerns relevant to all uses of investigational GTs in children. Here, we review the main ethical issues, specifically those surrounding the current state of knowledge about GT product-related immunogenicity, toxicity, duration, irreversibility, informed consent/assent, trial design (including the question of who 'goes first'), participant and caregiver burdens, and equity in diagnosis and access to research opportunities. Ethical issues that can be anticipated to arise in pediatric GT clinical trials, e.g., the uncertainty and risk of this research, the resultant preclusion of GT trial participants from other research, the length of follow-up monitoring, and the urgency often felt by caregivers dealing with dire, rapidly progressive conditions, should be proactively identified, addressed in accordance with existing best practices, and transparently discussed among all stakeholders.


Assuntos
Consentimento Livre e Esclarecido , Projetos de Pesquisa , Criança , Humanos , Cuidadores , Ética em Pesquisa , Ensaios Clínicos como Assunto
6.
JAMA Netw Open ; 5(11): e2239766, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36318206

RESUMO

Importance: The expanded access (EA) pathway permits patients to be treated with investigational medical products outside clinical trials. Because cancer care is a common indication for which EA is sought and these efforts require physician management, understanding oncologists' perspectives can help illuminate factors influencing patient access. Objective: To learn how oncologists practicing at academic medical centers (AMCs) perceive EA and their role in offering it. Design, Setting, and Participants: This qualitative study used data from semistructured interviews conducted from February 2020 to September 2021 with a purposive sample of oncologists recruited from large, urban AMCs in the northeast United States. Oncologists who had submitted at least 1 single-patient EA request to the institutional review boards at the University of Pennsylvania, Children's Hospital of Philadelphia, NYU Langone Health, and Dana-Farber Cancer Institute from January 1, 2014, through January 31, 2020, were eligible to participate. Data were analyzed from July 2021 to March 2022. Main Outcomes and Measures: Interviews focused on oncologist practice demographics, experience with EA, factors relevant to decisions to pursue EA and comfort with those decisions, perspectives on oncologists' role in EA, perspectives on the FDA's role, and the Right to Try pathway to access investigational drugs. Results: Eligible oncologists were interviewed until thematic saturation was reached, resulting in 25 interviews; most participants were women (15 participants [60%]), reported primarily treating adult patients (15 participants [60%]), had more than 10 years of clinical experience (16 participants [64%]), and had submitted at least 2 single-patient EA requests to their institutional review boards during the relevant period (14 participants [56%]). Oncologists viewed EA as an important tool for securing what they determined to be the best treatment option for their patients based on their own expert assessment of available data. Interviewees reported that they would rather access interventions as commercially available products or through clinical trials; however, if the preferred option was not available through these means, they viewed pursuit of EA as part of their obligation to patients, while often recognizing the potential for inequities in the broader patient population beyond their institutions. Participating oncologists felt confident pursuing investigational drugs for treatment use, despite the absence of FDA marketing approval, and did not necessarily view EA as a last resort. Conclusions and Relevance: These findings indicate that oncologists practicing in large academic settings sought to treat patients with the interventions they deemed most likely to be beneficial, regardless of approval status. As such, they viewed EA as an unexceptional means to obtain promising products, although it remains unclear whether their confidence in evaluating investigational treatments was justified. Future research should examine whether oncologists outside large AMCs share this confidence, as differences may influence patient access to the EA treatment pathway.


Assuntos
Drogas em Investigação , Oncologistas , Adulto , Criança , Humanos , Feminino , Masculino , Ensaios de Uso Compassivo , Organizações , Projetos de Pesquisa
7.
Nucleic Acid Ther ; 32(2): 111-117, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34797685

RESUMO

The first individualized therapy was administered in the United States just 2 years ago, when milasen, a therapeutic adapted from a Food and Drug Administration (FDA)-approved antisense oligonucleotide technology, was developed for a young girl with an extremely rare genetic mutation associated with Batten disease. Since then there has been an explosion of enthusiasm in developing customized treatments for extremely rare genetic conditions. These interventions raise some of the ethics concerns characteristic of novel therapeutics while simultaneously challenging existing legal, regulatory, and ethical understandings. Their individualized aspect blurs to the point of erasing the historically distinct line separating research from treatment, leading regulators and ethics oversight bodies to reevaluate existing policies. As experimental therapeutics, they raise the potential for both compromised informed consent and conflicts of interest, and their considerable expense provokes serious justice concerns. This article examines these challenges, urges multidisciplinary stakeholder engagement to address them in a transparent and practicable manner, and recommends initial policy responses.


Assuntos
Consentimento Livre e Esclarecido , Doenças Raras , Humanos , Políticas , Doenças Raras/genética , Doenças Raras/terapia , Participação dos Interessados , Estados Unidos
9.
Am J Bioeth ; 21(12): 4-19, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34665689

RESUMO

After witnessing extraordinary scientific and regulatory efforts to speed development of and access to new COVID-19 interventions, patients facing other serious diseases have begun to ask "where's our Operation Warp Speed?" and "why isn't Emergency Use Authorization an option for our health crises?" Although this pandemic bears a number of unique features, the response to COVID-19 offers translatable lessons, in both its successes and failures, for non-pandemic diseases. These include the importance of collaborating across sectors, supporting the highest-priority research efforts, adopting rigorous and innovative trial designs, and sharing reliable information quickly. In addition, the regulatory response to the pandemic demonstrates that lowering standards for marketing authorization can result in increased safety concerns, missed opportunities for research and treatment, and delays in determining what works. Accordingly, policymakers and patient advocates seeking to build on the COVID-19 experience for non-pandemic diseases with unmet treatment needs should focus their efforts on promoting robust and efficient research designs, improving access to clinical trials, and facilitating use of the Food and Drug Administration's existing Expanded Access pathway.


Assuntos
COVID-19 , Pandemias , Desenvolvimento de Medicamentos , Humanos , SARS-CoV-2
11.
Med Access Point Care ; 5: 23992026211005991, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-36204503

RESUMO

Introduction: Physicians in the United States play an essential role guiding patients through single patient pre-approval access (PAA) to investigational medical products via either the Food and Drug Administration (FDA)'s Expanded Access (EA) or the federal Right To Try (RTT) pathways. In this study, we sought to better understand pediatric hematologist/oncologists' attitudes about seeking PAA, on behalf of single patients, to investigational drugs outside of clinical trials. Methods: A cross-sectional survey was developed and sent to pediatric hematologist/oncologists via St. Baldrick's Foundation's email distribution list. Results: Of 73 respondents (10.1% of those who received the survey), 56 met eligibility criteria and are included in the analysis. Over 80% (n = 46) had prior experience with single patient PAA. Respondents were most concerned about the unknown risks and benefits of investigational drugs and financial implications of PAA for patients. One hundred percent and 91.1% of respondents indicated a willingness to support patients through EA and RTT pathways, respectively. When asked about their most recent experience with PAA, 40 out of 46 indicated that they used the FDA's EA pathway to seek PAA and 4 out of 46 indicated that they used the RTT pathway. Of 44 respondents who had used the EA or RTT pathway, 43 indicated that the biotechnology or pharmaceutical company they solicited granted access to the requested product. Conclusion: Survey results support other findings suggesting a need for additional physician support and education about PAA and that physicians may have unequal access to information about investigational drugs and concerns about financial implications of PAA for their patients.

13.
Science ; 370(6523): 1423-1424, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33335058
14.
Regen Med ; 15(8): 1979-1985, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33023369

RESUMO

Aim: The US FDA has two nontrial pre-approval access pathways: expanded access (EA) and right to try (RTT). Reports of successful RTT use are scarce, and the FDA has not yet published RTT usage data, yet proponents tout its utility. In the face of this discrepancy and a lack of transparency of usage statistics, our aim is to add to the limited understanding of RTT usage. Materials & m ethods: We searched crowdfunding campaigns referencing 'expanded access', 'right to try' or 'compassionate use' since 2018. Results: We identified 26 EA campaigns, 29 RTT campaigns and two referencing both. Twenty one EA campaigns described being approved to receive access to the requested experimental medical product versus one RTT campaign. Conclusion: RTT is associated with poor understanding of nontrial pre-approval access. These campaigns suggest RTT is not offering a practical alternative to EA. Cost remains a significant barrier to these patients.


Assuntos
Autorização Prévia , Humanos , Estados Unidos , United States Food and Drug Administration
17.
Am J Public Health ; 110(8): 1198-1204, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32552017

RESUMO

This article examines the origins and context of mandatory bicycle helmet laws in the United States. Localities began to enact such laws in the early 1990s, having experimented with helmet laws for motorcycles previously. As cycling became increasingly popular in the 1970s and 1980s because of a variety of historical trends, from improved cycle technology to growing environmental consciousness, cycling-related injuries also increased. Bicycle safety advocates and researchers alike were particularly troubled by head injuries. National injury surveillance systems and a growing body of medical literature on bicycle-related injuries motivated a number of physicians, cyclists, children, and other community members to advocate helmet laws, which they argued would save lives. Controversy over these laws, particularly over whether they should apply universally or only to children, raised public health ethics concerns that persist in contemporary debates over bicycle helmet policies. (Am J Public Health. 2020;110:1198-1204. doi: 10.2105/AJPH.2020.305718).


Assuntos
Ciclismo/lesões , Traumatismos Craniocerebrais/epidemiologia , Regulamentação Governamental/história , Dispositivos de Proteção da Cabeça/história , Adolescente , Adulto , Criança , Traumatismos Craniocerebrais/prevenção & controle , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Estados Unidos/epidemiologia
18.
Ethics Hum Res ; 42(1): 2-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31967412

RESUMO

For decades, the U.S. Food and Drug Administration (FDA) has provided an "expanded access" pathway that allows patients who meet qualifying conditions to gain access outside a clinical trial to an investigational medical product being tested to see if it is safe and effective for a specific use. The Right to Try (RTT) Act, enacted in 2018, created a second mechanism for off-trial, or non-trial, access to investigational drugs. In contrast to the expanded access pathway, the federal RTT pathway does not require the involvement of the FDA or an institutional review board (IRB). Given that physicians, drug manufacturers, and medical institutions now have a choice whether to assist individual patients through the expanded access or the federal RTT pathway, we review the differences between these options and discuss the benefits and burdens of IRB involvement in requests to access interventions through the pathways. We also suggest ways in which IRB oversight may be further improved.


Assuntos
Ensaios de Uso Compassivo , Drogas em Investigação , Pesquisa , Humanos , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência
19.
Med Microecol ; 62020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33834162

RESUMO

Fecal microbiota transplantation (FMT) has rapidly grown in notoriety and popularity worldwide as a treatment for both recurrent and refractory C. difficile infection (CDI), as well as for a myriad of other indications, with varying levels of evidence to justify its use. At present, FMT use in the U.S. has not received marketing approval from the U.S. Food and Drug Administration (FDA), but is permitted under "enforcement discretion" for CDI not responding to standard therapy. Meanwhile, the rising interest in the gut microbiome throughout mainstream media has paved the way for "do-it-yourself" (DIY) adaptations of the procedure. This access and unregulated use, often outside any clinical supervision, has quickly outpaced the medical community's research and regulatory efforts. While some studies have been able to demonstrate the success of FMT in treating conditions other than CDI-studies on ulcerative colitis have been particularly promising-little is still known about the treatmen's mechanism of action or long-term side effects. Likewise, screening of donor stool is in its early stages in terms of protocol standardization. In this paper, we explore the regulatory and ethical concerns that arise from the need to balance access to a nascent but promising innovative treatment with the need for research into its efficacy, risk profile, and long-term impact.

20.
Acad Med ; 95(1): 44-51, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31599758

RESUMO

Medical school faculty and their colleagues in schools of nursing, public health, social work, and elsewhere often research issues of critical importance to health and science policy. When academics engage with government policymakers to advocate for change based on their research, however, they may find themselves engaged in "lobbying," thereby entering a complex environment of legal requirements and institutional policies that they may not fully understand. To promote academic advocacy, this article explains what is and is not legally permitted when it comes to engaging with policymakers and encourages academic institutions to facilitate permissible advocacy activities.U.S. law permits academic researchers to conduct certain types of policy-focused advocacy without running afoul of legal restrictions on lobbying. Academics acting in their personal capacities and with their own resources may freely engage with policymakers in any branch of government to provide their expertise and advocate for desired outcomes. When acting in their professional capacities, academics are free to engage in most advocacy activities directed to the executive and judicial branches, and they also may advocate to influence legislation and legislators within certain limits that are particularly relevant to academic work. In all cases, academics must take care to not use restricted funds for lobbying.Academic researchers have an important role to play in advancing evidence-based health and science policy. They should familiarize themselves with legal restrictions and opportunities to influence policy based on their research, and their institutions should actively support them in doing so.


Assuntos
Política de Saúde/legislação & jurisprudência , Manobras Políticas , Ciência/legislação & jurisprudência , Academias e Institutos/organização & administração , Pessoal Administrativo/legislação & jurisprudência , Pessoal Administrativo/normas , Defesa do Consumidor/legislação & jurisprudência , Prática Clínica Baseada em Evidências/legislação & jurisprudência , Docentes de Medicina/normas , Apoio Financeiro , Programas Governamentais , Humanos , Saúde Pública/legislação & jurisprudência , Pesquisadores/legislação & jurisprudência , Faculdades de Medicina/normas , Escolas de Enfermagem/normas , Serviço Social , Estados Unidos/epidemiologia
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