Pharma Gets The Lowdown On New EMA Processes For Proactive Publication Of Clinical Trial Data
This article was originally published in SRA
The European Medicines Agency has finalized guidance to help implement its policy on the proactive publication of clinical trial data from drug applications submitted for approval from January 20151,2.
The guidance has been issued with the aim of helping drug companies navigate the new processes and procedures introduced by the EMA in relation to the policy, under which the first clinical trial reports are expected to be made public in mid-September3.
The guidance will ensure that pharmaceutical companies are aware of what is expected of them so that they are ready to support the publication of these critical data, said the EMA's Deputy Executive Director Noël Wathion.
As a next step, the EMA will now start reaching out to companies that will be affected by the first wave of publication clinical reports – i.e., sponsors of those medicinal products for which the decision-making process has been finalized since the policy entered into force in January 2015.
In addition, the agency plans to organize a webinar in the second quarter of 2016 to allow companies to "ask any outstanding practical questions" regarding the policy.
The guidance document itself is 91 pages long and contains several templates, flowcharts and fictitious examples in relation to the policy. Specifically, it explains how drug companies should: identify and redact commercially confidential information (CCI) in clinical reports; anonymize personal data; and follow procedures for submitting clinical reports.
In addition, it offers clarification on certain specific situations, like the applicability of the policy in relation to:
- Legacy documents: Any "legacy" document that is used for supporting a marketing authorization application submitted after Jan. 1, 2015 will also be made public. The legacy documents will be published irrespective of who owns the right to these documents. In cases where only a cross-reference is made to clinical reports previously submitted in another procedure, there will be no need for companies to resubmit the cross-referred clinical report for the sole purpose of publication under the policy.
- Duplicate marketing authorizations: Provided that there are no differences among the clinical study reports for the concerned duplicate products, the submission of one redaction proposal for all such documents will be sufficient. The clinical study report should be accompanied by a statement confirming that the same set of documents was filed for all duplicate marketing authorizations (bearing different invented names).
- Informed consent documents: The policy does not apply to informed consent applications where only Module 1 (of the common technical document) is submitted.
Redacting Information
The EMA will play a proactive role in implementing the policy and will take the first step of notifying the concerned company that it needs to submit a "redaction proposal document" package to the agency. In the package, the company should include proposed redacted versions of all clinical reports relating to the finalized regulatory procedure along with a number of additional documents.
After receiving the package, the EMA will assess the redactions proposed by the company. It is important that companies clearly indicate the redaction being requested and justify their request by filling out a separate "justification table", the EMA says.
The guidance document explains how companies should prepare justifications to support their proposed redactions. It also contains a non-exhaustive list of the most frequent data elements that are considered commercially confidential by companies during the access to documents consultation process, but which the EMA does not consider to be CCI. These include:
- Structural formula of active metabolites and metabolic pathways (unless the manufacturing process of the active substance can be deduced from the disclosure of the structural formula).
- Information on scientific advice received from any regulatory agency during the development of the product related to the approved indication. This includes information on the design and conduct of completed studies for which the results were submitted within the regulatory application package, the timing of requesting/obtaining the scientific advice, and the names of the agencies that issued the scientific advice.
- Primary and secondary endpoints, including biomarkers and exploratory endpoints.
- Information on the purpose and outcome of audits and inspections carried out during the conduct of clinical trials, including the audit plans.
- Literature reviews, meta-analyses and pooled data analyses supporting certain study design elements or certain safety and efficacy claims.
- Safety-related information such as adverse reactions (presented in various forms such as aggregated data or within case narratives) regardless of whether they are reflected in the approved product information or whether they were observed in clinical trials or reported after authorization.
- Safety-related information/case narratives, even where the described case is related to "off label use" or indications subject to ongoing development plans.
Once the company proposes redactions, there will be a consultation process to allow the EMA to thoroughly assess the validity of the proposed redactions and to enable the company to communicate clearly why, in its view, the information proposed for redaction is considered commercially confidential.
After the redactions are agreed upon, the company will have to submit a "final redacted document" package, which will be the final version of the clinical reports for publication in which redactions have been carried out by the company using a redaction tool.
If a company disagrees with the EMA's conclusion on what is considered CCI and should have been redacted, it can file an application for annulment of the EMA's decision and a related application for interim relief to the General Court of the European Union within a specific timeframe. In such cases, the company should submit a partial "final redacted version" package for publication.
In exceptional situations where companies do not submit a complete "redaction proposal document" package or a complete "final redacted document" package, the EMA will publish a non-compliance notice.
Personal Data
The guidance also addresses the question of anonymizing personal data in clinical trial reports. It says that there are two options for establishing whether data has been anonymized. One is by showing effective anonymisation based on three criteria:
- Possibility to single out an individual.
- Possibility to link records relating to an individual.
- Whether information can be inferred concerning an individual.
The other option, where a proposal does not meet one of these criteria, is to establish effective anonymisation through an evaluation of the identification risks.
"An anonymisation solution preventing all three criteria is considered to be robust against identification performed by the most likely and reasonable means the data controller or any third party may employ, and will render the data anonymous," the guidance states.
It also stresses the importance of taking into account advances in technology, such as data mining, together with the greater availability of data and the possibility of database linkage with a consequent increased risk of re-identification. Companies need to "take into account (realistic) future developments in terms of availability of data and technologies that would allow identification," it says.
References
1. EMA press release, March 3, 2016, www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2016/03/news_detail_002481.jsp&mid=WC0b01ac058004d5c1
2. External guidance on the implementation of the European Medicines Agency policy on the publication of clinical data for medicinal products for human use (EMA/90915/2016), March 2, 2016, www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2016/03/WC500202621.pdf
3. EMA's Policy On Proactive Publication Of Clinical Data: First Reports To Be Made Public In Mid-Sept, Scrip Regulatory Affairs, Feb. 1, 2016