EMA Revises Guidance on Biomarkers for Alzheimer’s Therapies

March 12, 2018

The EMA’s Committee for Medicinal Products for Human Use revised its guideline on the clinical investigation of treatments for Alzheimer’s disease, focusing on the design and analysis of safety studies and the potential use of biomarkers in various stages of development. The revision, which takes effect on September 1, separates biomarkers according to their potential use: diagnostic, enrichment, prognostic, predictive and pharmacodynamic. The guideline notes that while most biomarkers still require validation for these purposes, cerebrospinal fluid markers, as well as MRI and PET imaging markers, “are qualified for the enrichment of study populations,” even though the biomarkers have not been qualified for use in preclinical Alzheimer’s disease. Identified adverse events should be categorized in relation to the treatment duration, applied dosage, recovery time, different age groups and other variables, the guideline said, and all adverse events occurring during clinical trials should be fully documented with a separate analysis of adverse drug events that lead to drop-outs and fatal outcomes. The revised guideline is available here:

NHS Harmonizes CTA Templates Across England, Scotland, Wales and Northern Ireland
A new Model Clinical Trials Agreement from the NHS’ Health Research Authority will allow a single model contract for commercial R&D to be used in England, Scotland, Wales and Northern Ireland, unlike the 2011 nation-specific versions. The revised templates are designed to be used without modification for industry-sponsored trials in patients in hospitals throughout the health service. The Association for the British Pharmaceutical Industry said it hopes the updated agreement, which took effect March 1, will be used by companies and NHS research sites without changes to reduce the time for clinical trial start-up. The HRA expects sites to continue to accept unmodified 2011 versions of the template, while sponsors and CROs finalize their transition to the new version.

FDA to Host Public Meeting on Complex, Innovative Trial Designs
The FDA is holding a public meeting March 20 on the use of complex, innovative clinical trial designs, to inform regulatory decision-making, the development of a pilot program and a guidance document required by the 21st Century Cures Act. The meeting sessions will be held at the FDA’s White Oak campus and will focus on adaptive designs; the use of external or historical control subjects, Bayesian designs and master protocols; and simulations for confirmatory trial design and planning. The meeting will be split into four sessions: Using Prior Data from Early Phase Trials to Inform Phase III Designs; Utilizing Patient Registry and Natural History Study Data to Advance Therapeutic Development for Rare Diseases; Leveraging Master Protocols for Trials with Small Patient Populations; and Additional Topics for Consideration in Rare Disease Settings. The Cures Act directs the FDA to develop guidance addressing the use of complex trial designs, ways sponsors may obtain feedback on technical issues related to simulations, the submission of resulting information, the types of quantitative information that should be submitted for review and recommended analysis methodologies, the agency said. The meeting is also intended to meet a PDUFA VI performance goal. More information can be found here:

Oxford Researchers Identify Discrepancies Between and the EUCTR
Approximately one-sixth of clinical trials registered on both and the EU Clinical Trials Register have discrepancies in their completion status, according to a study published in PLOS ONE. Researchers from the Evidence-Based Medicine DataLab at the University of Oxford found multiple errors and omissions while comparing 10,492 clinical trials registered on both systems — 16.2 percent had differing completion statuses, and 33.9 percent of trials in both systems listed as “ongoing” on EUCTR were listed as “completed” on While it is unclear whether researchers, registry owners or both are responsible, the authors recommended that researchers request clarifications from the trialists, and that registries should cross-check data to ensure accuracy. The EBM DataLab recently launched its FDAAA Trials Tracker, which details U.S. studies that have not disclosed their results within one year of completion (CWWeekly, March 5). The full PLOS ONE article is available here:

Novartis, Science 37 Expand Partnership for 10 Virtual Clinical Trials in Three Years
Novartis is expanding its alliance with Science 37 to initiate up to 10 new clinical trials over the next three years, blending virtual and traditional models while working toward a site-less model. The two companies previously initiated virtual trials for cluster headaches, acne and nonalcoholic steatohepatitis.Virtual trials use digital technology to allow certain trial aspects to be performed at home or a physician’s office, rather than a trial site. The new trials are expected to begin later this year in dermatology, neuroscience and oncology, with plans to allow patients to participate using mobile devices and telemedicine services.

Parexel Co-Founder Josef von Rickenbach to Step Down as CEO
Josef von Rickenbach, co-founder of Parexel, announced plans to step down as CEO last week, while continuing to serve as chairman of the board. The company appointed Jamie Macdonald to succeed him, effective March 15. Macdonald led INC Research, now known as Syneos Health, first as CEO and then as vice chairman, helping to take the company public in 2014. Before that, he served as the company’s chief operating officer. Macdonald has also served as senior vice president and head of global project Management at Quintiles, now known as IQVIA, and as chairman of the Association of Clinical Research Organizations board of directors in 2015. Von Rickenbach co-founded Parexel in 1982, and helped to expand the company to a valuation of over $5 billion dollars, with operations in over 100 countries.