Struggling with extensive informed consent procedures for cancer trials-is there even a benefit for the patients?

PURPOSE: Informed consent procedures in clinical trials often differ in length and complexity to those in clinical routine care. Little is known about the benefit of extensive procedures as intended in clinical trials compared to procedures in routine cancer treatment. METHODS: In two different clinical studies performed at a comprehensive cancer center, we compared patients' comprehension and satisfaction of current informed consent procedures in routine clinical care with the level of comprehension and satisfaction of patients treated within clinical trials. Patients with a new cancer diagnosis and recent informed consent received a questionnaire about satisfaction, comprehension, time management, and physician-patient relationship of the informed consent process. Patients in cohort 1 consented to cancer treatment within a clinical trial and were additionally interviewed in a structured way; patients in cohort 2 consented to "standard" chemotherapy and received a follow-up questionnaire after 6 months. RESULTS: In cohort 1, 82 patients completed the questionnaire and had an additional structured interview. They were treated in 41 different trials, receiving up to 40 pages of educational material. In cohort 2, 89 patients completed the first and 52 completed the follow-up questionnaire after receiving a standard informed consent form of 6 pages. Subjective understanding and satisfaction with the information provided was equally very high. However, deficits in objective understanding were observed in both cohorts. CONCLUSION: Extensive informed consent procedures for clinical cancer trials have not been associated with a higher level of satisfaction or measurable objective understanding; therefore, the benefit seems to be limited.

Any progress in informed consenting for cancer treatment? Results from a cross sectional analysis at a comprehensive cancer center.

PURPOSE: Informed consent is required prior to any medical procedure. In the context of cancer treatment, special efforts are needed to inform cancer patients properly about treatment, potential sequelae and alternative therapies. Little is known about the effectiveness of current informed consent strategies and patients' individual satisfaction. Given the heterogeneity in terms of age, education, sex and other factors, detailed understanding of patients' comprehension and perception is the basis for further optimization of the informed consent process, which was the aim of the current investigation. METHODS: Patients with a new cancer diagnosis and recent informed consent were asked to complete a questionnaire about satisfaction, comprehension, time management, physician-patient relationship and other items of the informed consent process. Patients were followed for 6 months and invited to complete a follow-up questionnaire. RESULTS: In total, 89 patients completed the first questionnaire and 52 the follow-up questionnaire. Subjective understanding was assumed high, however, this did not correlate with objective understanding. Age and education were identified as influencing factors for comprehension. 85% of the patients were satisfied with the information provided. A major gap was the information on alternative therapies. Moreover, not all patients perceived the consent dialog as such, and particularly the individual treatment intention partially remained unclear for some patients. CONCLUSIONS: To ensure that informed consent is based on solid understanding, informed consenting must be patient-centered and consider the individual expectations, needs and abilities of cancer patients. Further studies are required to develop tailored informed consent strategies.

Life-threatening disseminated enterovirus infection during combined rituximab and ibrutinib maintenance treatment for mantle cell lymphoma: a case report.

BACKGROUND: Rituximab is a well-established component of treatment regimens for B-cell non-Hodgkin lymphoma. Rituximab binds the CD20 antigen on the surface of B lymphocytes, causing an enhanced clearance of malignant and benign B cells. Thus, rituximab leads to depletion of normal B lymphocytes as well, which can cause substantial immunodeficiency. Ibrutinib inhibits the Bruton tyrosine kinase and thereby B-cell activity. It is used for the treatment of different B-lymphocyte malignancies, such as mantle cell lymphoma. Recently, the combination of both drugs has been tested in various clinical scenarios. CASE PRESENTATION: We present a case of disseminated enterovirus infection resulting from combined rituximab and ibrutinib maintenance treatment in a 57-year-old Caucasian patient. with mantle cell lymphoma. Initially presenting with myositis symptoms, further diagnostic investigation revealed myocarditis, enteritis, myeloencephalitis, and hepatitis. These organ manifestations led to potentially life-threatening complications such as rhabdomyolysis, delirium, and heart rhythm disturbances. After treatment with high-dose intravenous immunoglobulins, virus clearance was achieved and organ functions could be restored. CONCLUSIONS: This case emphasizes the risk of combined therapy with rituximab/ibrutinib for severe immune-related side effects with the necessity of continuous patient monitoring. High-dose intravenous therapy should be considered as treatment for severe enterovirus infection. In severe enterovirus infections, we recommend subtyping for the development of efficient preventive and therapeutic strategies.

Control of organ transplant-associated graft-versus-host disease by activated host lymphocyte infusions.

BACKGROUND: Prolonged persistence of donor-derived T cells after organ transplantation has been proposed to improve long-term allograft survival. However, surviving transplant-derived T cells are also able to mediate devastating graft-versus-host disease (GvHD). Currently, GvHD after organ transplantation is usually refractory to conventional therapy and the disease outcome fatal. METHODS: Graft-reactive host T cells were generated ex vivo from a patient suffering from a severe and refractory liver-transplant-associated GvHD. To control GvHD, activated alloreactive host T cells were repetitively retransferred into the patient (activated host lymphocyte infusion [aHLI]). RESULTS: Adoptive transfer of ex vivo activated alloreactive host T cells (aHLI) led to the control and complete resolution of severe GvHD without inducing allograft rejection. CONCLUSIONS: aHLI opens a novel therapeutic window to control solid-organ transplant-associated GvHD while preserving allograft integrity.