Current Challenges in European Clinical Trials: CTIS and Ethics Committees
Alex Forrest Head of Industry Practices and Life Sciences, Chubb Overseas General
The Clinical Trials Information System (CTIS) opened to submissions in January 2022 and offers a workspace for clinical trials sponsors in the EU to compile and submit their clinical trial applications. The system was intended to be a single-entry point for submission and assessment of multinational and multi-jurisdictional trials, with a publicly accessible website providing information on clinical trials taking place in the EU and EEA. Submission via this system has been mandatory for new clinical trials applications since January 2023.
Twelve months on, how has CTIS been performing and how has it impacted clinical trials insurers?
How are the challenges of the Clinical Trials Information System in Europe impacting life sciences insurers?
The issues created by CTIS impact not only us at Chubb, but all life sciences insurers in the clinical trials market. CTIS functions rather differently from the EU Clinical Trials Register that it replaced. Gone is the need to submit individual clinical trial applications to each country or jurisdiction. Instead, one application is required for all countries in scope, no matter how many or how few.
It’s this change that has been the most impactful and the most problematic. While it seems to be less administratively burdensome on sponsors, Contract Research Organisations (CROs), brokers and insurers, the reality is that the overall burden is unchanged but the pressure is much greater for all involved parties. Insurance is usually the last consideration when planning a clinical trial, and the initial request is often received with very little notice. In our experience, we have found that it can be extremely complicated to collate all the information required to insure clinical trials in multiple countries or jurisdictions. Once the risk has been bound, it can be a challenge to obtain certificates from multiple countries within a very short space of time. Now that CTIS requires all countries to be included at once, this has increased insurers’ workloads considerably.
Another significant challenge presented by CTIS is that once an application is submitted, should an ethics committee or regulator request changes, there is only a ten-day window in which to make and deliver those changes. This puts a great deal of pressure on CROs and insurers if the policies or certificates need amending. Understanding what changes need to be made, actioning them and re-generating insurance documents for multiple countries can be very tricky and put a lot of strain on underwriters.
Related challenges affecting clinical trials insurers
There are three related challenges impacting clinical trials insurers that we have found to be the most significant. First, since the CTIS rollout, we have increasingly found that CROs tend to assign responsibility for multiple countries or regions in a clinical trial to one co-ordinator, rather than allocating one co-ordinator to each country or jurisdiction in the trial as they did before. This means that the co-ordinator responsible for a clinical trial may not be familiar with the insurance or regulatory particularities of each country within their purview. On a number of occasions, we have dealt with clinical trial co-ordinators who are not based in or familiar with many of the countries in scope. Their gaps in knowledge can further delay the process of collating all the necessary insurance documents for each country.
Second, in the recent past we have seen more clinical trial cancellations than usual, which can be attributed to many factors, a significant one being recruitment issues. While a certain number of cancellations are expected due to the nature of clinical trials, the high numbers of cancellations we are seeing may indicate that clinical trial applications via CTIS are being submitted with more countries included than will be utilised. Higher numbers of cancellations mean that the significant amount of work that goes into binding risk in each country for the submission – by insurers, brokers, CROs and sponsors – is wasted.
Lastly, an already existing issue that we have often come across – the inconsistency of ethics committees – has been exacerbated by CTIS. As countries have different clinical trial regulations and vary wildly in their application, obtaining approval from ethics committees in some countries is harder than in others.
What is the future of clinical trials in Europe?
It is reasonable to assume that the upward trend in cancellations will continue if the CTIS process does not change. Furthermore, it may be the case that pharmaceutical or medical device companies are disincentivised from undertaking clinical trials in certain EU countries. For example, if a sponsor or CRO is aware of a country that has an abstruse ethics committee, they may opt not to include that country in their clinical trial plans. This landscape may also encourage sponsors to conduct a greater proportion of their clinical trials outside of Europe, opting for countries such as Australia or Singapore.
The challenges to clinical trials caused by CTIS have shifted the key commercial consideration in clinical trials insurance from premium to service. Because of this, insurers may face barriers to entry in the market if they struggle to offer the quick turnaround required. For insurers like us who are already in the market, they may struggle to maintain their place due to the strain put on their services by CTIS.
What can be done to mitigate the common problems in clinical trial approvals?
Like all insurers in this space, at Chubb we are under immense time pressure to fulfil clinical trials insurance requests. As mentioned above, initial requests for coverage often come through very late into the clinical trial planning process, sometimes with only a matter of hours to assess the risk, produce a quote and bind. Insurance is often thought of as the last action to take prior to CTIS submission, but we would advise against this approach.
If insurers were part of the clinical trial plan from an earlier stage, it would be more beneficial to customers’ CTIS applications. The more time that insurers have to understand and bind a risk is inversely proportional to the margin for error. At Chubb, we are adept at issuing certificates and policies very quickly, but we would still benefit from longer lead times to prepare the required documents in advance.
While the intentions of the new CTIS process are reasonable, the impact of the new system over the last 12 months has been problematic for insurers, CROs and sponsors alike. The labour-intensive practice has resulted in a huge increase in time pressure on those involved in clinical trials approval submissions. The system has also exacerbated existing issues with ethics committees and, again, added more time pressure to respond to their queries.
I hope that the CTIS process will be amended to provide more flexibility in the approvals process. If ethics committees were subject to standardisation, that would also benefit clinical trials approvals. Standardisation would enable those applying to better anticipate committee queries and respond quickly – something that is very challenging in the current system.
All content in this material is for general information purposes only. It does not constitute personal advice or a recommendation to any individual or business of any product or service. Please refer to the policy documentation issued for full terms and conditions of coverage.