Upcoming European Clinical Data Transparency Regulations - How to Prepare

May 12, 2014

Background

A recent initiative (April 2014) by the European Medicine Agency (EMA) on data transparency was finally passed into draft law by the European Union, requiring that detailed summaries of clinical trials are published in a publicly accessible database once marketing authorization is granted. Sponsors could face strict fines for not complying. Also, in March 2014, the EMA published the first summary of a risk management plan (RMP) for a newly authorized medicine, stating “the Agency will pilot the publishing of RMP summaries for all newly centrally authorized medicines during 2014 and at a later stage will start producing RMP summaries for previously authorized medicines”. The RMP will be a publicly available document that describes all that is known and unknown about a drug’s safety and what actions will be taken to monitor the drug on the market and mitigate any risks.

These latest developments signal a significant step towards greater clinical data transparency in the European Union. The ultimate aim is to make it mandatory for Sponsors to respond to reasonable requests from the public to access the data, not just the results, collected during clinical trials. For this reason, clinical trial Sponsors need to evaluate whether they are prepared for the upcoming legislation which is anticipated to take effect in 2016.

The EU states its objective in the opening section of the legislation, “In a clinical trial the rights, safety, dignity and well-being of subjects should be protected and data generated should be reliable and robust.” Ensuring clear traceability of clinical data is therefore imperative to satisfying not just the EMA but also EU law. Being mindful of this requirement from Phase I will pay dividends for Sponsors later on. CROS NT is a strong advocate of centralizing data from the outset because it has seen so many of its customers benefit from this approach in terms of efficiency, cost savings, standardization and regulatory approval. For Sponsors selling the product license to a larger pharmaceutical company a centralized approach can enhance the value of the intellectual property because everything is in the one place, fully traceable and due diligence ready.

Preparing Your Data - Biometrics

Centralize clinical data from the start

If one study team is assigned to statistical trial design, data management, data analysis and medical communications from the start, common data standards can be applied throughout the drug development process. Continuity of team members creates a consistent style of medical communications and important collaboration between statisticians, data managers and medical writers. All data are stored in a central data warehouse and/or archive which avoids having to keep track of multiple repositories.

Centralizing clinical data in the early phases of drug development facilitates better integration of studies across all phases with common assessment methods, uniform traceability of data as well as the centralization of study metrics and study reports.

Ensuring traceability for regulatory submissions

In order for data to be transparent to the public, it must also be traceable. Implementing CDISC standards helps both traceability and cross analysis of datasets. There must be clear traceability from analysis results, to analysis datasets, and to SDTM datasets.

There are two types of traceability: data-point traceability and metadata traceability. ADaM datasets allow for the creation of variable or observations that are not directly used for the statistical analysis but support traceability. For example, re-allocation of data may happen for early termination visits in accordance with the Statistical Analysis Plan whereby both original visit name and re-allocated visit name are kept within the ADaM dataset. Metadata traceability includes documentation required to clearly describe information that already exists in the SDTM database together with algorithms and methods used to derive an analysis result.

Preparing Your Data - Integrating Technology

Clinical Data Visualization

Clinical data visualization can be an important component for Sponsors conducting trials in Europe who need to make more informed decisions and make sense of clinical data which could eventually be shared publicly. Conducting a trial generally leads to data being spread across multiple databases including EDC, CTMS, ePRO, safety databases, etc and if a centralized approach is not employed, such databases can be spread across multiple vendors and countries.

Data visualization tools facilitate drill-down and click-through to multiple levels of detail, allowing for the analysis of specific subsets and sub-populations. Customizable dashboards allow the clinical team to create ad hoc reports on site performance, data quality, safety and efficacy, drug supply, patient management etc.

Using data visualization tools, clinical leaders can see information that is beyond the capability of the CTMS report set. They also facilitate Risk Based Monitoring which vastly improves data quality and cuts monitoring costs. Most importantly, they allow clinical study teams to make crucial decisions from the information and trends revealed during the study rather than at the end.

Centralized Storage

If the EU legislation takes effect, Sponsors will need to be able to produce data for publication in an EU database. If all trial data are already centralized then they will be indexed, traceable and transportable. This means they can be easily transferred to a publicly accessible database. Centralized storage can produce additional benefits like greater efficiency and cost reduction. Review cycles can be reduced with standardization. Sponsors can also avoid paying for multiple global library set-ups, programming macros and validation checks.



Author: Chris Hamilton, Global Head of Business Development & Marketing, CROS NT