The changing world of cancer drug development: the regulatory bodies' perspective.

Background: Although not a singular disease entity, advanced cancer continues to be a largely intractable disease and a high unmet medical need situation. Discovery of novel therapeutic modalities, including new drugs targeting cancer, is undoubtedly of major public health interest.

Methods: In this article, we discuss current trends in oncology drug development as these are ultimately reflected in regulatory drug approvals.

Assessment of benefits and risks in development of targeted therapies for cancer--The view of regulatory authorities.

Drug licensing and approval decisions involve the balancing of benefits against the risks (harms) in the presence of uncertainty. Typically, the benefits are estimated from primary efficacy endpoints from confirmatory (phase III) clinical trials although exceptions where promising early data from single-arm studies have led to accelerated approvals are not uncommon, particularly for cancer drugs. The challenge for regulators is to balance early evidence of efficacy that might support approval versus the need to establish clinical benefit based on conclusive evidence.

Cancer drug development and the evolving regulatory framework for companion diagnostics in the European union.

The European Union (EU) legal framework for medical device regulation is currently under revision. The European Commission has proposed a new framework to ensure that medical devices serve the needs and ensure the safety of European citizens, aiming for a framework that is fit for purpose, more transparent, and better adapted to scientific and technological progress. The proposed new framework is described as an evolution of the current regime keeping the same legal approach.

The European Medicines Agency review of vemurafenib (Zelboraf®) for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma: summary of the scientific assessment of the Committee for Medicinal Products for Human Use.

The applicant company Roche Registration Ltd. submitted to the European Medicines Agency (EMA) an application for marketing authorisation for vemurafenib. Vemurafenib is a low molecular weight, orally available, inhibitor of oncogenic V600 BRAF serine-threonine kinase.

Hurdles in anticancer drug development from a regulatory perspective.

Between January 2001 and January 2012, 48 new medicinal products for cancer treatment were licensed within the EU, and 77 new indications were granted for products already licensed. In some cases, a major improvement to existing therapies was achieved, for example, trastuzumab in breast cancer. In other cases, new fields for effective drug therapy opened up, such as in chronic myeloid leukemia, and renal-cell carcinoma.

Qualification opinion of novel methodologies in the predementia stage of Alzheimer's disease: cerebro-spinal-fluid related biomarkers for drugs affecting amyloid burden--regulatory considerations by European Medicines Agency focusing in improving benefit/risk in regulatory trials.

The European Medicines Agency (EMA) in London is responsible for the Regulatory review of new medicinal products for Marketing Authorisation, through which pharmaceutical companies may obtain first Marketing Authorisation and subsequent Variations valid throughout the EU and EFTA. The qualification opinion of novel methodologies is a new procedure where applicants can obtain scientific advice on new methodologies for regulatory clinical trials of efficacy of new compounds. It will help benefit/risk assessment of the CHMP.

The European Medicines Agency: an overview of its mission, responsibilities, and recent initiatives in cancer drug regulation.

The European Medicines Agency (EMA) is responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the European Union (EU). Since 2005, the agency has become responsible for the approval of all new oncology drugs in the EU. In this article we describe the mission, role, and responsibilities of the EMA, and provide a brief summary of recent initiatives related to cancer drug regulation.

Hand position on steering wheel during driving.

Objective: The objective was to study hand position on the steering wheel during driving and differences in hand position within and between the genders.

Methods: This cross-sectional pilot study was conducted in Ornskoldsvik, Sweden. Photos were taken of drivers on a public road with a speed limit of 70 km/h, and hand position and gender were registered.

Backset-stationary and during car driving.

Objectives: The aim of the study was to measure and analyze backset, defined as the horizontal distance between the back of the occupant's head and a point located on the ventral/top aspect of the sewn rim of the head restraint, with the car stationary and during driving, in the driver's position in a modern car.

Methods: A population of 65 subjects, 35 males and 30 females, was studied in a Volvo V70 car, model year 2007. The subjects were studied in the driver's position, in a self-selected posture.

Seat adjustment--capacity and repeatability among occupants in a modern car.

Families in the Western world have a car and several family members share the same car. In this study, 154 participants have adjusted a driver's seat three times. The primary objective was to study intrapersonal repeatability and intraclass correlation (ICC) on seat; length adjustment, backrest angle, seat front edge and seat rear edge adjustment, related to participant age, sex, stature and weight.

Erythropoietin therapy and cancer related anaemia: updated Swedish recommendations.

Due to concerns related to treatment with erythropoietin (EPO) and possible negative effects on tumour control, a workshop was organised by the Medical Products Agency of Sweden with the aim to revise national treatment guidelines if needed. In patients with solid tumours, conflicting results have been reported with respect to tumour control and survival. Until further notice it is therefore recommended that EPO should be used restrictively in the treatment of patients with cancer and that the anticipated improvement in quality of life should be evaluated against potential risks.

Backset and cervical retraction capacity among occupants in a modern car.

Objectives: The horizontal distance between the back of the head and the frontal of the head restraint (backset) and rearward head movement relative to the torso (cervical retraction) were studied in different occupant postures and positions in a modern car.

Methods: A stratified randomized population of 154 test subjects was studied in a Volvo V70 year model 2003 car, in driver, front passenger, and rear passenger position. In each position, the subjects adopted (i) a self-selected posture, (ii) a sagging posture, and (iii) an erect posture.

Placebo-controlled trials and the Declaration of Helsinki.

A revised version of the Declaration of Helsinki, issued in October, 2000, remains a vital expression of medical ethics, and deserves unanimous support. A strict interpretation of the declaration seems to rule out clinical trials that use a placebo control group whenever licensed therapeutic methods already exist, preferring active controls. Although the efficacy of some new medicines can be satisfactorily established without the use of a placebo, for others the judicious use of placebo remains essential to establish their effectiveness.