Unproven stem cell therapies: is it my right to try?

BACKGROUND: Nowadays one of the most critical aspects of innovative cell-based therapies is the unregulated industry, as it is becoming a competitor of the regulated system. Many private clinics, worldwide, advertise and offer cell-based interventions treatments directly to the consumer and this poses a risk to both vulnerable patients and health systems. Several countries have implemented Compassionate Use Programmes (CUP) that provide patients with medicines that have not yet completed the approval pathway, in the event that no reasonable alternative exists. Recently, in the public discourse, compassionate use has been increasingly associated with a patient's right to try. Thus, the aim of this study was to assess public knowledge of the clinical trials process with specific reference to innovative stem cell treatments, and trust in the institutions responsible for regulatory activities. We also asked people about their "right" to use unregulated therapies. METHODS: We developed an ad hoc questionnaire on three main areas of concern and administered it to 300 people in the patient waiting room at an Italian university hospital. RESULTS: Our findings suggest that people have a good knowledge of the clinical trials process and trust in healthcare institutions. Nonetheless, one person in two believes it is a right to use unregulated therapies. CONCLUSIONS: We stress the need, in the age of cellular therapies, for a commitment to support vulnerable patients and to strengthen awareness among the public about the substantial boundary that differentiates experimental therapies from unproven therapies. There should not be a "right to try" something that is unsafe but rather approved treatments and in line with good clinical practice. The trend, which emerged on this issue from our study, is quite different, confirming the urgent need to improve health information so that it is as complete as possible.

Compassionate use of gene therapies in pediatrics: An ethical analysis.

In this commentary, we raise concerns about the compassionate use of CRISPR-mediated gene therapies in pediatric and perinatal patients. There is already a precedent for obtaining gene therapies for pediatric patients through compassionate use programs, and the recent passage of a federal Right to Try law may contribute to an increase in the number of patients who seek access to investigational products outside of a clinical trial. Clinicians, nurses, drug companies, and parents need support as they grapple with whether compassionate use of CRISPR-mediated gene therapies is the right thing to pursue for a child. We raise three issues to consider in that decision: (1) the effects of compassionate use on scientific research; (2) hype and harms of gene therapies; and (3) the limits and scope of parental authority.

Fair, just and compassionate: A pilot for making allocation decisions for patients requesting experimental drugs outside of clinical trials.

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or 'preapproval', access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet platforms enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients' best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee (CompAC). Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice.

Compassionate use programs in Italy: ethical guidelines.

BACKGROUND: This article proposes a retrospective analysis of a compassionate use (CU), using a case study of request for Avelumab for a patient suffering from Merkel Cell Carcinoma. The study is the result of a discussion within a Provincial Ethics Committee (EC) following the finding of a high number of requests for CU program. The primary objective of the study is to illustrate the specific ethical and clinical profiles that emerge from the compassionate use program (CUP) issue. The secondary goals are: a) to promote a moral reflection among physicians who require approval for the CUP and b) provide the basis for recommendations on how to request CUP. MAIN BODY: The instruments for carrying out the analysis of the case study and the discussion are as follows: Analysis of the audio-recording of the EC meeting regarding the selected Case study. In-depth discussion of topics that emerged during the meeting by means of administration of 5 semi-structured interviews with 2 doctors involved in the case (proposing physician and palliative physician) and with 3 components of the EC who played a major role in the EC internal discussion. CONCLUSIONS: In an exploration of emerging clinical and ethical issues, four primary themes arise: 1. efficacy, safety of the treatment and patient's quality of life; 2. clear, realistic, adequate communication; 3. right to hope; 4. simultaneous Palliative Care approach. The results of ethical analysis carried out concern two areas: 1) ethical profiles relating to the use of CUP; 2) the role of the EC concerning the compassionate use of drugs and the need to provide recommendations on how to request CUP. With the aim of implementing these conclusions, the provincial EC of Reggio Emilia chose to steer the request for drugs for compassionate use through recommendations for good clinical and ethical practice based on the following assumptions: 1) the "simultaneous care" approach must be preferred. Secondly, 2) the EC's assessment must be part of the decision-making process that the care team conducts before proposing compassionate use to the patient.

Seguridad y efecto del uso compasivo del anticuerpo monoclonal anti-CD20 CIMABior® / Safety and response to treatment of compassionate use of an anti-CD20 monoclonal antibody CIMABior®

Introducción: el uso de anticuerpos monoclonales transformó el tratamiento de los linfomas no hodgkinianos. El Centro de Inmunología Molecular generó un anticuerpo anti-CD20 (CIMABior®) biosimilar del rituximab, que se ha caracterizado desde el punto de vista biológico, pero la seguridad y eficacia aún están en estudio. Objetivo: evaluar la seguridad y la respuesta al tratamiento con CIMABior ®, en pacientes con síndromes linfoproliferativos de células B tratados con intención compasiva. Métodos: estudio multicéntrico, exploratorio, con dos grupos de tratamiento (monoterapia o combinado con quimioterapia) no controlado, ni aleatorizado. Se incluyeron adultos con linfomas no hodgkinianos y leucemia linfocítica crónica, no elegibles para el ensayo clínico en ejecución con este producto. Se determinó la frecuencia de eventos adversos y se caracterizaron. La respuesta al tratamiento se definió como: remisión completa, remisión parcial, enfermedad estable o en progresión. Se calculó la tasa de respuesta objetiva (remisión completa más remisión parcial) con el intervalo de confianza al 95 por ciento, se evaluó la relación de algunas variables con la respuesta y se estimó la razón de Odss. Como medida de balance beneficio-riesgo se estimó el factor de Bayes. Resultados: los eventos adversos más frecuentes fueron: temblor (12,8 por ciento) y fiebre (10,3 por ciento). Los relacionados con el producto (43,4 por ciento) fueron leves o moderados y evolucionaron hacia la recuperación. No se informó muerte asociada directamente al tratamiento. Se constató respuesta objetiva global de 71,2 por ciento (59,6 por ciento de remisiones completas y 11,5 por ciento, parciales). La respuesta objetiva en el grupo de monoterapia fue de 66,7 por ciento y de 73,0 por ciento en el grupo de CIMABior® más quimioterapia, con remisiones completas de 46,7 por ciento y 64,9 por ciento, respectivamente. Conclusiones: el AcM CIMABior® es seguro, bien tolerado y se demostraron evidencias de efecto. El tratamiento aportó un beneficio clínico superior al riesgo de desarrollar algún evento adverso grave(AU)

Introduction : The use of monoclonal antibodies transformed the treatment of non-Hodgkin lymphomas. The Center of Molecular Immunology created an anti-CD20 monoclonal antibody (CIMABior®), biosimilar of rituximab, which has been characterized from a biological point of view, but the safety and effectiveness are still being studied. Objective: Evaluate the safety and response to treatment, in patients with B-cell malignancies with compassionate use of CIMABior®. Methods : A multicenter, exploratory, non-controlled, non-randomized study was conducted with two variants of treatments (monotherapy or combined with chemotherapy). Adults with non-Hodgkin lymphomas and chronic lymphocytic leukemia not eligible for clinical trial with this product were included. Frequency of adverse events was calculated and those were characterized. The response to treatment was defined as: complete response, partial response, stable disease or progressive disease. Overall response rate (complete plus partial remission) was calculated with 95 percent confidence interval. The relation of some variables with response was estimated per Odss ratio. As a measure of the benefit-risk balance, the Bayes factor was estimated. Results : The more frequent adverse events were: tremors (12.8 percent) and fever (10.3 percent). Those related to the product (43.4 percent) were minor and evolved to recovery. There were no deaths in reference to the treatment. An overall response of 71.2 percent was confirmed (59.6 percent complete remissions and 11.5 percent partial remission). The monotherapy group objective response was 66.7 percent and 73.0 percent in the CIMABior® plus chemotherapy group, with complete remissions of 46.7 percent and 64.9 percent respectively. Conclusions: The monoclonal antibodies CIMABor® is safe, well tolerated and evidences of its effectiveness was demonstrated. The treatment provided a superior clinical benefit to the risk of developing a severe adverse event(AU)

One Last Shot.

Texas' right-to-try law makes experimental drugs more accessible to terminally ill patients when all other FDA-approved treatment options are unavailable or are unlikely to prolong life.

Examining the ethics of clinical use of unproven interventions outside of clinical trials during the Ebola epidemic.

The recent Ebola outbreak in West Africa began in the spring of 2014 and has since caused the deaths of over 6,000 people. Since there are no approved treatments or prevention modalities specifically targeted at Ebola Virus Disease (EVD), debate has focused on whether unproven interventions should be offered to Ebola patients outside of clinical trials. Those engaged in the debate have responded rapidly to a complex and evolving crisis, however, and this debate has not provided much opportunity for in-depth analysis. Additionally, the existing literature on access to unproven therapies has focused on contexts like HIV/AIDS and oncology, which are very different than the Ebola epidemic. In this paper, we examine the ethical issues surrounding access to unproven therapies in the context of the recent Ebola outbreak to yield new insights about this controversial and unsettled issue. We argue first that, in this context, the interests of patients in obtaining access to unproven therapies are not fully aligned with the interests of their providers and drug developers. Second, we focus on the resource constraints facing providers, funders, and patients and conclude that they often counsel against the use of unproven interventions against EVD.

Dilemmas in the compassionate supply of investigational cancer drugs.

In Australia, patients who want to access medicines that are not yet approved have only two options: to enroll in a clinical trial if they are eligible, or obtain their medicine through 'compassionate supply', which is provided at the discretion of the manufacturer. In this article, we explore ethical issues associated with the provision of oncology medicines that are still in development, either prior to regulatory approval or government reimbursement.

ABOUT PATIENTS, "INVENTORS", JOURNALISTS, SCIENTISTS AND IRBs (TO SAY NOTHING OF THE INSTITUTIONS): CCSVI AND MS.

In this article, the Author analyzes her own experience as a member of the IRB that approved a trial to determine the efficacy of a disobstruction procedure of extracranial veins by means of angioplasty in patients with multiple sclerosis (MS). The so-called "liberation therapy" was proposed by an Italian vascular surgeon, who theorized a condition called "chronic cerebrospinal venous insufficiency" (CCSVI) as playing a role in the pathogenesis of MS. This approval, given after an animated discussion amongst IRB members, lacked any solid scientific evidence of a causal relationship between CCSVI and MS, and was accepted despite the concerns about potential risks associated with the proposed therapy. Undoubtedly, considerable pressure was exerted on IRB by MS sufferers, who rushed off to get the surgery from the many clinics who offered liberation therapy.The remaining sense of bitter has raised a reflection on how to prevent similar future cases.