Quantitative and qualitative analysis of study-related patient information sheets in randomised neuro-oncology phase III-trials.

INTRODUCTION: In randomised controlled trials (RCTs), patient informed consent documents are an essential cornerstone of the study flow. However, these documents are often oversized in format and content. Clinical experience suggests that study information sheets are often not used as an aid to decision-making due to their complexity. MATERIAL AND METHODS: We analysed nine patient informed consent documents from clinical neuro-oncological phase III-studies running at a German Brain Tumour Centre with the objective to investigate the quality of these documents. Text length, formal layout, readability, application of ethical and legal requirements, scientific evidence and social aspects were used as rating categories. Results were assessed quantitatively by two independents investigators and were depicted using net diagrams. RESULTS: All patient informed consent documents were of insufficient quality in all categories except that ethical and legal requirements were fulfilled. Notably, graduate levels were required to read and understand five of nine consent documents. DISCUSSION: Quality deficits were consistent between the individual study information texts. Irrespective of formal aspects, a document that is intended to inform and motivate patients to participate in a study needs to be well-structured and understandable. We therefore strongly mandate to re-design patient informed consent documents in a patient-friendly way. Specifically, standardised components with a scientific foundation should be provided that could be retrieved at various times, adapted to the mode of treatment and the patient's knowledge, and could weigh information dependent of the stage of treatment decision.

Interferon-induced programmed death-ligand 1 (PD-L1/B7-H1) expression increases on human acute myeloid leukemia blast cells during treatment.

INTRODUCTION: While current treatment for acute myeloid leukemia is characterized by high response rates, patients' long-term outcome is still disappointing, due to frequent relapse and ineligibility of the often elderly patients for stem cell transplantation approaches. Considerable efforts have, thus, been made to incorporate immunotherapeutic approaches in the acute myeloid leukemia (AML) consolidation, with so far disappointing clinical benefit. The B7 family ligand programmed-death receptor-ligand 1 (PD-L1, B7-H1, CD274) has been recently described (with conflicting results) to be expressed on AML blast cells, and interaction with its receptor on T cells, programmed death receptor-1 (PD-1, CD279), has been shown to suppress T-cell functions and to allow survival of dormant AML cells in animal models. DESIGN AND METHODS: In this work, we analyzed freshly isolated myeloid precursor cells from healthy donors and from AML patients for PD-L1 expression with or without interferon-γ exposure at different time points during their treatment. RESULTS: While without IFN exposure, only minor differences were observed, we found IFN-γ-induced PD-L1 expression most prominent after initial treatment and independent of treatment outcome. CONCLUSIONS: Our observations support the recently suggested PD-L1-mediated adaptive immune resistance and argue for a targeting of the PD-L1/PD-1 pathway during the consolidation phase of AML treatment.