Global clinical trials present several opportunities to sponsors. Broader population pools and lower operational costs are two significant drivers behind a multinational approach to research. Indeed, many emerging markets have significant potential for sponsors. But managing patients in multiple parts of the world can be challenging when it comes to compliance.
We explore the growth in global clinical trials and what sponsors and trial managers need to do to ensure operational compliance.
The Appeal of Global Trials
As many as 48 percent of U.S.-sponsored trials are conducted in foreign countries and 35 percent were U.S.-only trials. The clinical trial market is in rapid flux and while Western Europe and the U.S. remain key target markets, China is rapidly growing in importance, explains Daniel O’Connor, founder of TrialSite News.
The shift towards global clinical trials is not surprising. While multinational trials present a potentially complex compliance landscape, they remain cost effective. David Alvaro, Ph.D., scientific editorial director at Nice Insight, says lower operational costs (salaries, facilities rent, documentation and training) are key to these cost savings. But there’s also the added boon of larger population pools and faster recruitment rates.
GDPR for Trials Involving EU Citizens
Consent Requirements
Data privacy and security is a global concern. Sponsors looking to run trials in the EU will need to ensure compliance with General Data Protection Regulation. Nigel Hughes, scientific director JCI-PDR at Janssen, says one of the major changes that GDPR has brought about is consent.
Obtaining patients’ personal health data needs consent. And consent needs to be asked for in plain and understandable language, documenting why the data is required, how it will be used and by whom, and where it will be stored. “Overall, it must be clear to any EU citizen what their data is being used for (lawfulness, fairness and transparency),” Hughes explains. Plus, patients should be able to easily withdraw their consent.
Pharma companies and CROs that get this wrong could face significant financial and reputational damage.
Challenges to Data Sharing
Still, GDPR is not straightforward, and in fact could even be hindering greater ambitions of data transparency and collaboration within the industry, writes Jill Weschler at Applied Clinical Trials. When multiple sponsors and products are involved in research, data tracking, analysis, disclosure, and privacy protection become challenging. Remaining compliant requires careful navigation of the requirements of several regulatory authorities.
For example, Weschler says that Health Canada is changing its process for the public release of clinical information. It’s similar but not identical to EU Policy 0070. The latter demands that trial results are shared as summary or aggregate data. The European Medicines Agency (EMA) and Health Canada are also sharing clinical study reports to support market applications for new drugs. But this method runs counter to FDA policies and the Common Rule for research funded by the U.S.
If these uncertainties are not made clear, running trials in the U.S. and EU could become harder, inhibiting collaboration between the two.
Safeguarding Data Transfers
The data of EU citizens that leaves the EU for third-party nations or international organizations requires safeguards — data protection clauses, legally binding instrument between public authorities, corporate rules — to be in place for the transfer to be compliant. Natasa Spasic, data protection officer at Pharm-Olam, says this is always the case unless the recipient of the data has received an adequacy decision from the European Commission.
For U.S. sponsors, standard data protection clauses should be Privacy Shield certified.
Particulars of the EU Regulatory Environment
While the EU has standardized rules governing its member states, there are still considerations that are particular to each country. Symbio Europe chief operating officer Veronika Kunert says that while EU 2001/20/EC concerns itself with the fundamental requirements, other nations may require stricter compliance.
Meeting these criteria can be worth the effort. For instance, Belgium helps to shorten the start of the study so enrolling the first patient can be achieved more quickly.
Cross-Border Collaboration After Brexit
The outcome of Brexit, at the time of writing, remains uncertain. Indeed, uncertainty is a growing concern for many, particularly for those involved in clinical research and medical treatment. UK member of Parliament Chris Green says successful clinical trials require cross-border collaboration and Brexit is threatening this.
He warns that patients need to come first, before broader political questions are answered. To ensure compliance and collaboration in a post-Brexit Europe, Green says pragmatism is required. That means trials should remain easy to set up and ensure the safety of patients whether they’re taking place in the UK or Europe.
The new Clinical Trial Regulation coming into effect in the EU involved contributions from the UK and the latter is likely to adopt the regulations regardless of what happens with Brexit. This will go a long way to ensuring compliance. As Green says, agreement on shared regulations and responsibilities would safeguard patients and allow researchers to continue their important work.
The Complexity of Global Data Disclosure
We’ve mentioned GDPR but each country requires specific compliance with data disclosure processes. As Thomas Wicks, chief strategy officer for TrialScope says, multinational trials complicate disclosure requirements.
First, compliance with multiple countries’ regulations requires resource allocation, and second, trial sponsors will also battle against the lack of standardization of data capture and reporting.
Changes in China
China, once a complex regulatory environment, has worked hard to streamline clinical trials for international sponsors. In the past four years, China has published more than 250 guidance documents and policies, says health journalist Nick Taylor.
Some of the changes include lifting restrictions on phase I trials to make early-phase research easier to manage in China, and abandoning a legacy system of certifying clinical trial sites. China has also adopted a U.S.-style clinical trial application system to shorten the waiting time between sponsors applying to conduct a study and being granted permission to do so.
He adds that the effectiveness of these changes will only be seen as more international sponsors begin to conduct trials in the country.
The Value of a Registered Importer
Multinational trials will require having a team on the ground in each of the relevant countries. An important position is the registered importer or importer of record, explains export compliance manager Dan Polkowski.
The challenge with the IOR is that many sponsors will never meet this person, but the relationship will be based on trust that compliance will be met. Failure to tick off the compliance boxes could result in research materials being held in a particular country’s customs office.
Polkowski warns that the IOR must be compliant with the country’s import regulations and requirements, especially concerning ancillary supplies, electronic and medical devices.
Preventing Corruption
In January 2019, nearly 50 percent of all clinical trials registered with the NIH were conducted outside of the U.S. With the international reach of many trials, there is greater risk of falling foul of anti-corruption laws, write Andrew Shaoyu Chen et al at Arnold Porter.
The lawyers note that international trials require governmental involvement through government-owned hospitals and national tenders for medical supplies, for example. Coupled with increased focus on international collaboration of authorities and growing concern from clinical research regulators, means that sponsors need to be risk-aware.
Many companies, however, have not taken steps to ensure they are compliant with anti-corruption regulations. Corruption can happen at nearly every stage of the research process, the lawyers note, and often includes illegal payments to government officials.
Sponsors and their CROs should ensure that they are both prepared to be scrutinized under anti-corruption laws, that they exercise due diligence over third-party research partners and that all payments adhere to FCPA, the UK Bribery Act and other anti-corruption laws.
Sourcing Comparators in Global Trials
Global clinical trials can run into problems when it comes to sourcing comparator drugs and rescue medications. If availability in a particular region is scarce, then sponsors will likely suffer long waiting times, says Tim Holmes, clinical supply manager at Rho.
Sponsors will also need to be sure that their medications do not expire during the trial so short-dated medications require staggered deliveries based on enrollment rates.
To achieve success in global trials, sponsors must align with global CROs or the relevant third-party partners in the countries in which the trial is being run. Careful selection of partners is vital. They need to be properly licensed, have global export and import capabilities, and clear connections to source drugs.
Global clinical trials will continue to grow in number as sponsors seek operational benefits. But compliance will remain a sticky issue until global standards are agreed to. The changes in China and the ambition of shared regulations between the EU and the UK are positive signs that global cooperation will continue.