Dose Transition Pathways: The Missing Link Between Complex Dose-Finding Designs and Simple Decision-Making.

The ever-increasing pace of development of novel therapies mandates efficient methodologies for assessment of their tolerability and activity. Evidence increasingly support the merits of model-based dose-finding designs in identifying the recommended phase II dose compared with conventional rule-based designs such as the 3 + 3 but despite this, their use remains limited. Here, we propose a useful tool, dose transition pathways (DTP), which helps overcome several commonly faced practical and methodologic challenges in the implementation of model-based designs.

Embracing model-based designs for dose-finding trials.

Background: Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM).

Methods: We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation.

Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: an update on cord blood unit selection, donor selection algorithms and conditioning protocols.

Allogeneic haemopoietic stem cell transplantation offers a potentially curative treatment option for a wide range of life-threatening malignant and non-malignant disorders of the bone marrow and immune system in patients of all ages. With rapidly emerging advances in the use of alternative donors, such as mismatched unrelated, cord blood and haploidentical donors, it is now possible to find a potential donor for almost all patients in whom an allograft is indicated. Therefore, for any specific patient, the transplant physician may be faced with a myriad of potential choices, including decisions concerning which donor to prioritize where there is more than one, the optimal selection of specific umbilical cord blood units and which conditioning and graft-versus-host disease prophylactic schedule to use.

Combined bezafibrate and medroxyprogesterone acetate have efficacy without haematological toxicity in elderly and relapsed acute myeloid leukaemia (AML).

Acute myeloid leukaemia (AML) causes life-threatening deficits of functional blood cells that require management using red cell and platelet transfusion and aggressive treatment of neutropenic infections. Current cytotoxic chemotherapy further worsens the problem of reduced haemopoiesis and two-thirds of patients are too frail to tolerate intensive chemotherapy at all. Median survival amongst these patients remains at <3 months emphasizing the urgent need for anti-AML therapies that do not suppress haemopoiesis.