How Merck Plans To Protect Commercial Info Under EU Clinical Trial Rules
Executive Summary
In the second segment of a two-part article on transparency provisions for the new EU clinical trial portal, a senior Merck executive explains how the company will ensure that commercially sensitive information and personal data in its clinical trial applications are not made public.
Merck KGaA has embarked on a mammoth two-part initiative to prepare for the expanded transparency requirements that will be embedded in the new EU Clinical Trial Information System (CTIS) when it goes live in December 2021.
Part one of the initiative involves reviewing and re-writing, where possible, all clinical trial-related templates and documents to reduce or eliminate references to any personal and commercially confidential data.
Part two relates to developing a company-wide policy on how Merck would seek to delay the publication of certain information in its clinical trial dossiers, which may be deemed as commercially sensitive in the initial stages of product development.
The CTIS portal, which is mandated under the EU Clinical Trial Regulation (No 536/2014), will be the single-entry point for submitting, assessing, authorizing, supervising and reporting clinical trials in all EU member states. (Also see "Launch Of EU Clinical Trial Portal Moves A Step Closer" - Pink Sheet, 19 Nov, 2020.)
Requests by sponsors to defer the publication of documents on grounds of commercial confidentiality, along with a legitimate justification, must be made at the time of submitting the trial application in the new portal.
“We still haven't decided on a set approach” for requesting deferrals, but are exploring all possible options, including tackling this on a case-by-case basis, said Sameer Sharma, clinical trial transparency manager at Merck in Germany.
Sharma was speaking at a virtual conference on the EU CTR organized by the Drug Information Association. The conference took place on 18-19 November. Merck is among the many companies that are also having to plan how they will protect commercially confidential and personal data in trial applications submitted via the CTIS. (Also see "EU Clinical Trial Portal Requires Rethink On Balancing Business Interests & Transparency" - Pink Sheet, 24 Nov, 2020.)
Merck has launched its two-part initiatives in response to the fact that almost all information in clinical trial applications submitted via the CTIS and evaluated under the CTR will eventually be made public. The only exceptions to this are personal data and some commercially confidential data (eg relating to quality aspects).
Merck’s initial focus is on the “content adjustment” of all documents flagged up “for publication” in the CTIS, Sharma said. The aim is to ensure that all personal and commercially confidential data in these documents, submitted as part of the clinical trial application, are removed or kept to the minimum possible level.
To implement content adjustment, he said that Merck set up a cross-functional workstream to deliver the necessary changes in the following three phases:
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- Identification – Merck’s team first defined the exact list of documents that will be made public under the CTIS. It then assigned a risk level based on the level of potential personal or commercially sensitive data these documents might contain.
- Mitigation – The team then agreed on possible mitigation actions, including re-writing documents meant “for publication” to reduce or remove references to personal and commercially sensitive data.
- Corrections – The team is currently in the midst of adapting templates and authoring guides of the documents affected by the mitigation actions. This will be followed by training that is being rolled out for related staff, Sharma said.
The “last critical piece” would be to “review and adjust our corrective measures” based on experience after the CTIS goes live, he added.
Room For Redactions
As clinical trial documents cannot be made “entirely free” of personal and commercial data, Sharma explained that Merck will also actively “perform redactions” to remove critical information from documents meant for publication.
To carry out redactions, he explained, the company will make use of the experience gained while implementing the European Medicines Agency’s “Policy 0070” on the proactive publication of clinical study reports. The EMA policy, although partially suspended at present, has resulted in most companies developing internal rules for data redaction and anonymization.
Merck wants to ensure that the rules it developed to comply with the EMA’s policy are aligned with its approach to supporting the transparency provisions in the CTIS. This will ensure that “we apply the same set of methodology… and parameters” to documents made public via the EMA’s Policy 0070 or via the CTIS, he said.
The EMA, however, does not support the redaction of commercially confidential data to prevent their publication under the CTIS, although it acknowledged that this approach is used in relation to Policy 0070.
According to EMA’s CTIS business expert Laura Pioppo, who also spoke at the conference, companies should ideally use the deferral mechanism in the CTIS to delay the publication of commercially confidential data for a certain period so that it can be eventually made public.
Under Policy 0070, Pioppo said she was aware that the “concept of redaction is sometimes applied not only for [removing] personal data, but also for what is considered commercially confidential information.”
For CTIS, if sponsors choose to redact commercially confidential data from documents meant for publication, this should be done in accordance with the agency’s guidance on redaction and anonymization of data in relation to Policy 0070, the EMA official said
Managing Deferrals
On the topic of submitting requests to defer the publication of trial documents on grounds of commercial confidentiality, Sharma warned that companies need to think about this carefully.
“You can be as careful as you like” by requesting that the publication of a document be deferred for the longest possible period, “only to find out that a version has become available elsewhere through other channels,” he said.
It may happen in cases where a company follows a “blanket approach” and comes up with a “standardized justification” to support the longest possible deferral requests as a default. In the case of Phase I trials, for example, the company can seek to defer the publication of the trial protocol for up to seven years after the end of the trial in the EU/European Economic Area.
However, if the company then submits a manuscript (relating to its Phase I trial) for publication in a scientific journal, “there is a requirement to submit the trial protocol along with the manuscript for review” and “the protocol would then be uploaded in a public domain afterwards,” Sharma explained.
The Merck executive believes that a more pragmatic approach would be to consider “transparency aspects beyond CITIS” and to then “accordingly request a deferral” on a case-by-case basis. However, “we still haven't decided on a set approach [for Merck],” he said.
For companies that opt for the case-by-case approach, he suggested one option would be to create a clinical trial transparency group, which could apprise the study/program team about the “transparency implications” of each trial. The program team could then “make an informed decision… on how a deferral would be requested for that particular trial.”
Outstanding Hot Topics
While the transparency features in the CTIS are based on the CTR, the EMA has identified certain changes or adjustments that may need to be made to the system later based on feedback from trial sponsors.
These issues, which are under active consideration by the EMA, include:
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- Flexibility on deferral timelines: Under the CTIS, the timelines for deferring the publication of a document once agreed, are fixed and cannot be changed. However, sponsors have expressed the need for flexibility on this front. At the end of a deferral period, for example, a company may feel that the information in the document still has commercial value and should not be published. Pioppo said the EMA was “considering the possibility to modify the deferral timelines.” This may be allowed in the context of a substantial modification or when a new EU member state concerned is added to the trial. No final decision has been made on this topic.
- Publication of scientific advice: There is ongoing discussion on whether a high-level summary of scientific advice provided to a sponsor on its clinical trial application can be published.
- Publishing each updated version of the deferred document, eg trial protocol: Discussions are also underway on whether to publish all the versions of a deferred document in a staggered way or whether all the versions should be published together.