Transfer of photosynthetic NADP/NADPH recycling activity to a porous metal oxide for highly specific, electrochemically-driven organic synthesis.

In a discovery of the transfer of chloroplast biosynthesis activity to an inorganic material, ferredoxin-NADP reductase (FNR), the pivotal redox flavoenzyme of photosynthetic CO assimilation, binds tightly within the pores of indium tin oxide (ITO) to produce an electrode for direct studies of the redox chemistry of the FAD active site, and fast, reversible and diffusion-controlled interconversion of NADP and NADPH in solution. The dynamic electrochemical properties of FNR and NADP(H) are thus revealed in a special way that enables facile coupling of selective, enzyme-catalysed organic synthesis to a controllable power source, as demonstrated by efficient synthesis of l-glutamate from 2-oxoglutarate and NH.

Preparing for success with comparative effectiveness research.

This commentary reviews the work on Comparative Effectiveness Research (CER) published in this issue by Gary Lyman and Scott Ramsey et al., concluding that CER will play a key role in optimizing outcomes for cancer patients in the future.

Making investments in medical technology: time to get real about real options.

The article by Grutters et al. on using real options analysis to investigate the adoption of medical technology in The Netherlands, published in this issue of , is reviewed.

Interpreting trial results in light of conflicting evidence: a Bayesian analysis of adjuvant chemotherapy for non-small-cell lung cancer.

Purpose: When successive randomized trials contradict prior evidence, clinicians may be unsure how to evaluate them: Does accumulating evidence warrant changing practice? An increasingly popular solution, Bayesian statistics quantitatively evaluate new results in context. This study provides a clinically relevant example of Bayesian methods.

Methods: Three recent non-small-cell lung cancer adjuvant chemotherapy trials were evaluated in light of prior conflicting data.

Promoting medical innovation while developing sound social and business policy: a conversation with Thomas G. Roberts. Interview by Barbara J. Culliton.

The development of "targeted biologics" as cancer therapy has made the field ripe for investment from the private sector and is changing the face of cancer medicine, while also raising important policy concerns about price, profit, and continued innovation. In this interview Barbara Culliton talks with Thomas Roberts, who sees this world from a unique perspective. Roberts, an oncologist, has practiced at the Massachusetts General Hospital and is currently thinking about innovation as a hedge fund manager.

Trends in the use and role of biomarkers in phase I oncology trials.

Purpose: There has been interest in using biomarkers that aid the evaluation of new anticancer agents. We evaluated trends in the use of biomarkers and their contribution to the main goals of phase I trials.

Experimental Design: We did a systematic review of abstracts submitted to the American Society of Clinical Oncology annual meeting from 1991 to 2002 and the publications related to these abstracts.

Economic evaluation of a Bayesian model to predict late-phase success of new chemical entities.

Objective: To evaluate the economic impact of a Bayesian network model designed to predict clinical success of a new chemical entity (NCE) based on pre-phase III data.

Methods: We trained our Bayesian network model on publicly accessible data on 503 NCEs, stratified by therapeutic class. We evaluated the sensitivity, specificity and accuracy of our model on an independent data set of 18 NCE-indication pairs, using prior probability data for the antineoplastic NCEs within the training set.

Timeline: Chemotherapy and the war on cancer.

The era of chemotherapy began in the 1940s with the first uses of nitrogen mustards and antifolate drugs. Cancer drug development since then has transformed from a low-budget, government-supported research effort to a high-stakes, multi-billion dollar industry. The targeted-therapy revolution has arrived, but the principles and limitations of chemotherapy discovered by the early researchers still apply.

Trends in the risks and benefits to patients with cancer participating in phase 1 clinical trials.

Context: In the past, cancer patients entering phase 1 studies confronted the prospects of high risk and unlikely benefit. Over the last decade, cancer drugs under development have become more targeted, and the clinical research environment has become more scrutinized. The impact of these changes on the risks and benefits to patients who participate in phase 1 cancer trials is unknown.

The phase III trial in the era of targeted therapy: unraveling the "go or no go" decision.

Purpose: To review characteristics of contemporary phase III oncology trials and create an explicit framework to help clinical researchers prioritize novel therapies for phase III testing.

Methods: We searched the MEDLINE and EMBASE databases for all reviews of phase III trials; cataloged all phase III trials in two national clinical trial databases; and reviewed approval criteria of recently approved oncology drugs from public data provided by the US Food and Drug Administration. Industry data not available elsewhere in the medical literature were obtained from a sourcebook published by a large contract research organization.