56 research outputs found
Nanoscale structure, dynamics and power conversion efficiency correlations in small molecule and oligomer-based photovoltaic devices
Photovoltaic functions in organic materials are intimately connected to interfacial morphologies of molecular packing in films on the nanometer scale and molecular levels. This review will focus on current studies on correlations of nanoscale morphologies in organic photovoltaic (OPV) materials with fundamental processes relevant to photovoltaic functions, such as light harvesting, exciton splitting, exciton diffusion, and charge separation (CS) and diffusion. Small molecule photovoltaic materials will be discussed here. The donor and acceptor materials in small molecule OPV devices can be fabricated in vacuum-deposited, multilayer, crystalline thin films, or spin-coated together to form blended bulk heterojunction (BHJ) films. These two methods result in very different morphologies of the solar cell active layers. There is still a formidable debate regarding which morphology is favored for OPV optimization. The morphology of the conducting films has been systematically altered; using variations of the techniques above, the whole spectrum of film qualities can be fabricated. It is possible to form a highly crystalline material, one which is completely amorphous, or an intermediate morphology. In this review, we will summarize the past key findings that have driven organic solar cell research and the current state-of-the-art of small molecule and conducting oligomer materials. We will also discuss the merits and drawbacks of these devices. Finally, we will highlight some works that directly compare the spectra and morphology of systematically elongated oligothiophene derivatives and compare these oligomers to their polymer counterparts. We hope this review will shed some new light on the morphology differences of these two systems
Considerations for Master Protocols Using External Controls
There has been an increasing use of master protocols in oncology clinical
trials because of its efficiency and flexibility to accelerate cancer drug
development. Depending on the study objective and design, a master protocol
trial can be a basket trial, an umbrella trial, a platform trial, or any other
form of trials in which multiple drugs and/or multiple subpopulations are
studied in parallel under a single protocol. External data and evidence (EDE)
can be used in the design and analysis of master protocols such as external
controls for treatment effect estimation, which can further improve efficiency
of the master protocol trial. This paper provides an overview of different
types of external controls and their unique features when used in master
protocols. Some key considerations in master protocols with external controls
are discussed including construction of estimands and assessment of fit-for-use
real-world data. A targeted learning-based causal roadmap is presented which
constitutes three key steps: (1) define a target statistical estimand that
aligns with the causal estimand for the study objective, (2) use an efficient
estimator to estimate the target statistical estimand and its uncertainty, and
(3) evaluate the impact of causal assumptions on the study conclusion by
performing a sensitivity analysis. Two illustrative examples are provided for
master protocols using external controls
Principal Stratum Strategy: Potential Role in Drug Development
A randomized trial allows estimation of the causal effect of an intervention
compared to a control in the overall population and in subpopulations defined
by baseline characteristics. Often, however, clinical questions also arise
regarding the treatment effect in subpopulations of patients, which would
experience clinical or disease related events post-randomization. Events that
occur after treatment initiation and potentially affect the interpretation or
the existence of the measurements are called {\it intercurrent events} in the
ICH E9(R1) guideline. If the intercurrent event is a consequence of treatment,
randomization alone is no longer sufficient to meaningfully estimate the
treatment effect. Analyses comparing the subgroups of patients without the
intercurrent events for intervention and control will not estimate a causal
effect. This is well known, but post-hoc analyses of this kind are commonly
performed in drug development. An alternative approach is the principal stratum
strategy, which classifies subjects according to their potential occurrence of
an intercurrent event on both study arms. We illustrate with examples that
questions formulated through principal strata occur naturally in drug
development and argue that approaching these questions with the ICH E9(R1)
estimand framework has the potential to lead to more transparent assumptions as
well as more adequate analyses and conclusions. In addition, we provide an
overview of assumptions required for estimation of effects in principal strata.
Most of these assumptions are unverifiable and should hence be based on solid
scientific understanding. Sensitivity analyses are needed to assess robustness
of conclusions
Association between response kinetics and outcomes in relapsed/refractory multiple myeloma: analysis from TOURMALINE-MM1
© The Author(s) 2018.The association between depth of response in multiple myeloma (MM) and long-term outcomes is well recognized [1,2,3]. Thus, clinicians and patients are often encouraged by a rapid decrease of M-protein when treatment is initiated, and achieving ≥very-good partial response (VGPR) by 4 months of initial diagnosis has been associated with decreased mortality [4]. However, little is known about the association between response kinetics and outcomes. While some reports suggest that early responders may have compromised long-term outcomes compared with late responders [5, 6], these studies were limited, confined to frontline setting only, and based in the era prior to novel-agent availability.TOURMALINE-MM1 was sponsored by Millennium Pharmaceuticals Inc. Writing assistance for this manuscript was provided by Jane Saunders, FireKite (an Ashfield Company, part of UDG Healthcare PLC) and was funded by Millennium Pharmaceuticals Inc
Phase 1 study of ixazomib, an investigational proteasome inhibitor, in advanced non-hematologic malignancies
Practical Considerations for Subgroups Quantification, Selection and Adaptive Enrichment in Confirmatory Trials
Topics in Applied Statistics2012 Symposium of the International Chinese Statistical Association /
XVII, 344 p. 75 illus., 60 illus. in color.onlin
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