The Global Cardiovascular Clinical Trialists Forum is a key event bringing together leading experts from across the spectrum of opinion leaders, clinical trialists, investigators, regulators, statisticians and practitioners to address the most pressing questions in cardiovascular clinical development today. At the December conference, eminent biostatisticians Cyrus Mehta and Stuart Pocock led a packed workshop tackling the advantages and limitations of adaptive designs within this space.
Jan 16, 2017 8:41:00 AM
Jan 5, 2017 8:45:00 AM
Nonlinear Mixed Effects Modeling (NONMEM) is a type of population pharmacokinetics/pharmacodynamics (popPK/PD) analysis used in Clinical Pharmacology research. The population PK approach combined with pharmacodynamics modeling, allows integrated analysis, interpretation, and prediction of the drug’s safety, efficacy, dose-concentration relationship, and dosing strategy.
Dec 23, 2016 8:21:00 AM
As we prepare to say 'so long, farewell' to 2016, we'd like to take the opportunity to thank all our blog readers and subscribers. Read on for a round up of our most read topics from the year....
Dec 21, 2016 9:45:00 AM
December 18th 2016 was a significant date for the pharmaceutical industry and regulatory submissions. For trials which commence after this date, the FDA will no longer accept non-CDISC data submissions for new drug applications ( NDAs) , certain investigational new drug applications, abbreviated new drug applications (ANDAs) and certain biologics license applications (BLAs).
The FDA guidance Providing Regulatory Submissions In Electronic Format — Standardized Study Data (1) also notes that the requirement will include ‘all subsequent submissions, including amendments, supplements, and reports’ to the submission types.
With regard to other regulatory agencies position on CDISC, the Japanese Pharmaceuticals and Medical Devices agency ( PMDA) will now request CDISC compliant submissions after October 2016 with a certain transitional period. This will be fully mandatory by 2018. While the European Medicines Agency (EMA) is adopting a top-down approach and therefore more focused on topics such as data transparency, issues of data integration and interoperability will also form part of the EMA’s future plans.
With this in mind, any sponsor planning an NDA, BLA or other regulatory submission needs to make sure they are observing best practice with regards to CDISC. In this blog, we outline some of the key issues to bear in mind as you prepare for your data submission.
Dec 20, 2016 9:21:00 AM
Data Standards play a crucial role in structuring and promoting long term value of clinical data.
Clinical Data Acquisitions Standards Harmonization or CDASH was developed with participation from all three ICH regions (US, Europe and Japan) with recommended data collection fields for 16 domains-> DEMOG, AE etc. It also includes implementation guidelines, best practice recommendations, and regulatory references. There is sometimes a misconception that CDASH defines the layout of the CRF and eCRF. This is not the case. The function of CDASH is to define the naming conventions for the clinical database, and outline how variables are mapped to SDTM. It defines how questions should be formulated for data collection within the CRF and eCRF making use of standard CDISC controlled terminology. In this blog, we will provide an example of CDASH implementation.
Dec 15, 2016 11:53:14 AM
In April, we interviewed NIHR research fellow Munya Dimairo about the paper, ‘Adaptive designs undertaken in clinical research: a review of registered clinical trials’ (Hatfield et al, 2016), for which Munya was a co-author.
During the previous interview, we discussed the barriers to uptake of adaptive designs, and the urgent need for a cross-sector discussion and work on reporting guidance of adaptive design. As a follow up to this, Munya is now Lead Investigator of the ACE project which aims to develop a consensus-driven reporting guidance tailored for Adaptive designs in the form of a CONSORT extension. The ACE Project is funded by the NIHR and is led by a multidisciplinary Steering Working Group of international experts in collaboration with the CONSORT Executive Group and the MRC HTMR Adaptive Designs Working Group. The goal is to enhance transparency, credibility, reproducibility, and replicability of adaptive trials as well as facilitate uptake of ADs in clinical trials research when appropriate.
We are delighted to welcome Munya Dimairo back to the blog to give us the inside scoop on this project.
Dec 13, 2016 8:18:00 AM
In the complex world of trial design and data analysis biostatisticians and data scientists need to ensure they are selecting and harnessing the best capabilities of the powerful software tools available to them. Particularly when non-standard approaches are required, this may mean using a combination of tools to come to the most appropriate solution for any task.
At the recent EARL conference, Cytel’s Aniruddha Deshmukh, Software Evangelist, discussed how R can be harnessed to extend and customize the powerful capabilities of East. Using R API , it’s possible to execute R code and manipulate R objects which are coded in other languages such as C/C++ and this approach has been used in East® to extend its features as well as customize simulations to meet any non-standard needs of a given clinical trial.
In this blog Aniruddha will take a techical look at R API and some of its key elements
Dec 6, 2016 10:18:00 AM
The management of quality clinical data collection is built on a number of core essentials- including project management, timeline management, understanding of the deliverables, alignment with statistics and selection of the right technologies. However, clinical development is a complex business and clinical data management approaches must be tailored to meet the specific needs of the trial. In this blog, we take a look at some of the key considerations to be addressed by data management across the different clinical development phases.
Dec 2, 2016 9:19:10 AM
At a recent Pfizer/ Cytel seminar on rare disease and oncology development, Cytel’s Lingyun Liu presented innovative work on a patient enrichment design. In this blog, we share some design and operational considerations. This approach can help mitigate against underpowering of a clinical trial where there is uncertainty and heterogeneity of treatment effect among subpopulations.
Nov 21, 2016 11:42:00 AM
While adaptive designs can deliver significant benefits to clinical development- including ethical benefits for patients, reduced costs, and improved likelihood of trial success- they are not suitable for every clinical trial. In making the assessment of whether or not to choose an adaptive design, trial planners need to weigh the strategic benefits against the practical implications.
We have previously discussed on the blog, the 10 steps proposed by Jim Bolognese and Ranganath Nayak to assist sponsors in making this decision. In this blog, we are delighted to share a simple infographic outlining the process.
Nov 18, 2016 10:04:00 AM
Our client had the following key questions which they wanted our pharmacometrics group to address for an upcoming phase 2 trial of their ulcerative colitis compound .
1) Can knowledge from pre-clinical and Phase 1 data inform on the optimal range of doses for an upcoming Phase 2 dose-ranging study?
2) How may the dose response observed in PD markers in Phase 1 healthy volunteers translate to the patient population?
Nov 14, 2016 8:13:29 AM
In our last blog, we shared some of Angelo Tinazzi and Cedric Marchand's recommendations on how to ensure independence of QC in statistical programming. Now, we've put together an infographic highlighting some key do's and don'ts in a handy checklist.
Nov 11, 2016 10:05:14 AM
A solid and robust QC process is one vital component of ensuring quality programming delivery. Angelo Tinazzi and Cedric Marchand presented at the PhUSE conference recently on the topic of ‘What Auditors want’. As part of this well received presentation, the duo discussed the question of independence of QC and how to make sure this is fully observed.
In this blog we’ll walk through their recommendations to ensure independence of QC in programming.
Nov 9, 2016 9:03:11 AM
Adaptive sample size re-estimation designs are an important part of the statistician's toolkit. In this first in a series of East Insight videos, Cytel Statistician Charles Liu walks us through the creation of an adaptive sample size re-estimation design in East with a 5 minute demo. Watch the video and download the accompanying slidedeck to recreate the steps.
Nov 1, 2016 10:02:00 AM
Unlike statistics which has been around in some form for hundreds of years, pharmacometrics is, by comparison, a relatively new discipline and only entered the clinical development world in the last 30 years. Situated at the intersection of mathematical modeling, simulation, and big data, pharmacometrics leverages the best practices of translational research to generate clinical development strategy.
Oct 25, 2016 7:59:00 AM
Use of R is a hot topic among statisticians and programmers in the pharmaceutical industry. At the recent PhUSE conference in Barcelona there was a clear uplift in interest in the language and a number of sessions explored introductory principles and examples of how R can be used in practice. Cytel's Namrata Deshpande presented on the use of R beyond Statistics through a case study of the development of a user friendly tool deploying non-statistical packages in R to enable clinical decision making. The talk won first prize in the Trends and Technology track at the PhUSE conference. In this blog, we'll discuss some of the aspects presented and share Namrata's slides for download.
Oct 18, 2016 9:38:00 AM
Oct 13, 2016 9:16:00 AM
Statistical programmers play a key role in turning the data from clinical trials into knowledge and supporting the development of new medicines. In a dynamic industry with demands such as CDISC compliance, data transparency initiatives, big data, and cost pressures the role is evolving to become ever more multi-dimensional. Statistical programmers now have the opportunity to follow their specific interests and specialize in a range of areas.
Oct 11, 2016 9:31:00 AM
Its important to take a strategic approach to clinical development in order to minimize the potential for Phase 3 attrition. The below infographic, previously published on the blog highlights some of the approvability and economic reasons cited for Phase 3 failure , and the clinical development issues which may have had an impact.
Oct 7, 2016 8:29:00 AM
Adaptive designs have the potential to accelerate clinical development, and improve the probability of trial success. While the principle is simple- to reduce the uncertainty in clinical development by obtaining additional information from the ongoing trial- the statistical methodologies can be complex, and expert support is often required to conduct the clinical trial design. There's also complexity in the data collection itself, so knowledgable data management support is needed to successfully execute an innovative trial design. In this blog, we take a look at 5 top considerations for successful adaptive trial data management.