Quanticate CRO Blog

Until 2007, the Food Drug & Administration (FDA) and the biopharmaceutical industry were grappled by the non-standardized sources of data. Gathering all the heterogenous data and mapping to the internal standards of the pharma companies proved to be the greatest challenge of the time. By the end of 2007, and towards the beginning of 2008, the Clinical Data Interchange Standards Consortium (CDISC) gained ground in its mission to develop a global set of standards. Eventually, CDISC began shaping the entire industry as FDA started requesting submission data in standardized formats, though CDISC compliant software options were limited.^1,2 The ‘study data standards’ provide a consistent general framework for organizing data, including templates for datasets, standard names for variables, identify appropriate controlled terminology and standard ways of doing calculations with common variables.³

The shift from paper to Electronic Data Capture (EDC) in the clinical trial world saw a shift in the way we look at the quality measurements of clinical data management (CDM) activities. The paper world had a clear understanding that the quality of the clinical data collected was simply the quality of the transcription work teams performed of transferring data from paper to a database. The Quality Control (QC) of paper versus database had a set standard for sampling of √N+1 or 20 subjects, whichever was smaller and a 100% QC of critical variables. Acceptable error rates were 0.5% which was widely agreed across the industry. These thresholds were no longer necessary when EDC enabled sites to enter the data directly and transcription was no longer needed. However, it is the role of the data management teams to be involved in many efforts to prepare data for appropriate analysis and submissions.

Welcome to our FiresideSTATS Podcast Episode 2. Today we are joined by our Statistical experts, Niccolo and Emily.

In 1992, the Food and Drug Administration (FDA) introduced four distinct and successful approaches known as Priority Review, Breakthrough Therapy, Accelerated Approval, and Fast Track approval of the investigational drug. Under the ‘accelerated approval’ regulation, surrogate endpoints for serious conditions that filled an unmet medical need are reviewed by FDA, allowing faster approval of drugs. A two-tiered system of review times – Standard Review and Priority Review were introduced by FDA under the Prescription Drug User Act (PDUFA). FDA reviews ‘Priority Review’ designated drugs within 6 months (compared to 10 months under standard review).^[i]

The leading cause of death in patients with coronavirus disease 2019 (COVID-19), caused by the virus ‘severe acute respiratory syndrome coronavirus 2’ (SARS‑CoV‑2), is respiratory failure from acute respiratory distress syndrome.^[1] Patients who required invasive mechanical ventilation had an 88% mortality rate in one study in New York, and a 53% mortality rate in one study in the UK.^[2][3] While an alarming proportion of patients with respiratory failure are dying, for the those who recover there is an urgent need to consider, and subsequently manage,  their longer-term care.^[4] Patients who have survived the COVID‑19 infection continue to experience feelings of fatigue, shortness of breath and reduced exercise tolerance. There is currently limited information regarding the best route to full recovery for post-coronavirus infection patients. Care will likely be multidisciplinary in nature and include a respiratory review along with physiotherapy, nutritional advice, psychiatric support, and potentially other disciplinary involvement.

Clinical Trial Design

The most common design used for Phase II and Phase III clinical trials is the randomized controlled trial design. In randomized controlled trials, the probability of being assigned the study treatment or the control treatment is fixed throughout the trial and is normally 50%, so that each treatment is given to the same number of patients. This approach leads to a high‑chance of identifying if one treatment is significantly better than the other. The fact that 50% of the trial population is assigned to the control treatment is not a particular issue in common diseases such as cardiovascular disease. For example, of the 7 million people in the United Kingdom (UK) with cardiovascular disease, if 200 of them are involved a clinical trial, then 99.9% of the overall cardiovascular disease population will benefit from the results of the clinical trial^[1].

The imminent application of Clinical Trial Regulation (EU) No. 536/2014, estimated to happen in 2020, will peak an emergent era of transparency in clinical development. The regulation applies to all interventional clinical trials (Phase 1 to 4) performed in the European Union (EU)/European Economic Area (EEA), plus additionally specified paediatric trials, and covers documents at the single clinical trial level irrespective of the drug’s marketing approval status. The regulation requires the disclosure of the study Protocol, Investigational Medicinal Product Dossier (IMPD; Sections S and E), Investigator’s Brochure (IB), Subject Information Sheet, Clinical Study Report (CSR; redacted) and a Plain Language Summary (PLS; also known as a Laypersons Summary) for each clinical trial within 12 months of the end of the trial (6 months for paediatric trials). Disclosure is readily welcomed by study participants who want to know what has been learned from their participation and is in accordance with the European Medicines Agency’s (EMA) goal of protecting and fostering public health by allowing better‑informed use of medicines. We will be able to learn from past successes as well as failures now that any biased under‑reporting of results will be stopped.