Health Canada aligns with EMA on public clinical trial reporting – with a few key differences
Shalini Dwivedi, Associate Director of Development Operations at Kinapse, and Pooja Phogat, Head of Development Operations, assess the implications of the draft guidance just published.
As life sciences firms continue to get to grips with their responsibilities around the public sharing of clinical study reports in EU markets, under EMA Policy 0070, the chance to broaden application of their emerging strategies and techniques is presenting itself across the Atlantic.
On April 10, Health Canada published its own draft guidance relating to the planned public release of clinical trial documents. It gives stakeholders a first proper look at how the national health authority intends to operationalise the regulations in Canada, and an opportunity to provide feedback. The draft guidance is open for public consultation until June 25 (comments can be submitted to firstname.lastname@example.org).
With a disclaimer that requirements could change as a result of feedback received during the public consultation, the initial guidance looks promising to sponsors that have already begun to invest in systematic approaches to managing public sharing of clinical trial documents in Europe. Here, the emphasis is evolving towards more sophisticated ways of anonymising study reports now, to ensure that published documents retain value for readers – while still protecting patient identities and potentially sensitive commercial information.
The signs are encouraging that Health Canada is adopting largely similar parameters for managing public disclosures of clinical studies, which should present opportunities for harmonising measures across regions. Although the US FDA is still at a pilot stage in its own data-sharing plans, the hope is that these too will be in step with Europe and Canada’s, minimising the additional investments global sponsors will need to make to keep everyone happy.
But there are some important differences between Health Canada’s proposed requirements and EMA Policy 070 guidance.
Key difference 1: medical devices are included
The first is that Health Canada is extending its requirements to include medical devices, whereas EMA Policy 0070 is solely concerned with drugs. So this will create new work for some companies previously unaffected by clinical trial data-sharing requirements.
The good news is that the Canadian authority plans to accept previously redacted documents submitted to the EMA. In such cases, sponsors would have to submit a certification based on a template provided in Health Canada guidance.
As the dossier structure follows the eCTD structure, the duplicate submission on Health Canada’s Common Electronic Submission Gateway would be relatively straightforward and sponsors would not need to duplicate their efforts. Medical device documents would be available in IMDRF-ToC format, including clinical information such as summaries, reports and evidence on medical device.
Key difference 2: tighter timescales for sponsors
The second significant difference involves the timescales. Under the measures being proposed in its draft guidance, Health Canada plans to be far less generous in the time it is allowing for sponsors to prepare publishable documents for the public portal.
For initial marketing authorisation applications (MAAs) and line extension applications, companies must submit their redaction proposal document package to EMA between day 181 and day 220 of the procedure (≤ 30 days pre-opinion and ≤ 10 days post-opinion). However, those publishing with Health Canada will have a maximum of 90 days in total: just 20 days for a positive opinion or 30+20 days for a negative opinion to produce a first submission, then a further 40 days to respond to feedback and submit a publishable version.
This contracted timeframe will heap on the pressure for responsible teams worried about striking the right balance between disclosure-related risk mitigation and ensuring documents are still meaningful and of value to interested parties.
Subtler sources of divergence
Health Canada is also keen to retain ultimate rights over what’s published. Whereas EMA effectively leaves the final decision with sponsors about what is anonymised in the final public output (they can take the judicial route if they are not aligned with the authority’s decision), Health Canada will give a sponsor one additional opportunity in the case of a proposed confidential information rejection but reserves the right to uphold or veto what’s included.
While EMA’s Policy 0070 is being rolled out in two phases, the second of which will cover individual patient data listings/case report forms, Health Canada appears not to share this ambition and will not share individual patient records proactively. As things stand, its aims are confined to broader trial reports. However it is considering new mechanisms through which patient-level data could be made available on request.
Health Canada’s implementation schedule has been designed to follow four steps:
Step 1 – Release of clinical information within drug submission for new active substances, supplemental new drug applications, and submissions to switch an authorized medicinal ingredient to non‐prescription status (Rx‐switch for full switch and partial switch submissions).
Step 2 – Release of clinical information within all new drug submissions (including those not categorised as new active substances).
Step 3 – Release of clinical information of all supplemental new drug submissions and Class IV medical device applications.
Step 4 – Release of clinical information on abbreviated new drug submissions and Class III medical device applications.
Health Canada is also concerned primarily with live/future submissions, rather than retrospective reporting – given that interested researchers/clinicians can chase down older findings through other routes if needed. (Although EMA Policy 0070 is similarly concerned only with MAAs effective from 1 Jan 2015, the European agency does have provision for retrospective reports under Policy 0043.)
However there may be cases when Health Canada demands public versions of interim reports – for instance, if an interim analysis that established clear superiority of the treatment for use and that is used to stop the trial early or an interim analysis of a clinical study that has been either completed or discontinued.
What to take away from the developments
Overall, sponsors with a global reach can feel justifiably relieved that Health Canada has not diverged significantly from EMA’s clinical trial data-sharing goals and planned processes. This offers some hope that the major agencies do appreciate the mutual benefits and opportunities that come from being in alignment. The biggest sign of this is that Health Canada has said it will accept existing EMA Policy 0070-approved submissions onto its own portal, albeit that these have to be submitted separately – rather than simply linked.
Assuming the consultation process doesn’t serve up any curve balls, we can expect Canada’s clinical trial data-sharing requirements to be formalised sometime next year. In the US, meanwhile, the Federal agency wants to be sure the whole concept of public disclosures is unequivocally worthwhile before it commits fully to the endeavour. It is currently in a pilot phase with nine sponsors, and the outcomes of this will determine what happens next.
But given the way things are developing in Canada the signs are that a consistency in intent and implementation approach is emerging, which supports the case for proceeding with systematic plans for document preparation and delivery. So they can have growing confidence in investing in their processes now.
There is a lot for firms to get right with all of this, so the sooner organisations set down optimum ways for managing publicly-publishable content, the better off they will be.