Clinical trials in the 21st Century are a rapidly evolving feast of technological and regulatory developments. But the basic complaints remain the same – bureaucratic, clunky, inconsistent. Patient recruitment is still a headache, trial complexity is a labyrinth, costs keep skyrocketing, and demands on the business model, with an emphasis on value, means research and development is under significant pressure. “It’s challenging to run clinical trials on a global basis,” explains Steve Cutler, chief executive of ICON.
Today, almost half of clinical trials take place outside the US as emerging countries heavily invest in healthcare and life sciences infrastructure, with testing and approval set on a global path, says Christian Hebenstreit, general manager and senior vice president EMEA at Medidata Solutions. “According to industry analysts, in the forecasted global market, developed countries are projected to account for about 66.8% [of trials] by 2020, down from 76% at present; whereas the emerging countries combined are projected to account for 25.2%, up from 15.7% at present.”
In a nutshell, global clinical trials aren’t just nice to have; they’re a necessary requirement, especially in terms of access to patients, patient population diversity, and getting a drug quickly picked up by more than one country. In other words, “access to larger patient populations allow sponsors to spread the risks related to volatile patient enrolment,” says Edoardo Madussi, commercial director, clinical trial services, at Inceptua. “From a clinical supply perspective, this means reducing the risk associated with drug supply forecasting. Having more regions involved allows quicker markets to move ahead, which in turn can imply quicker drug development timelines.” He adds: “Often clinical trials offer patients access to treatments they wouldn’t be able to receive otherwise, so the public health benefit is incredibly valuable.”
According to Hebenstreit, the globalisation of clinical trials is an “important consideration” in improving the efficiency of trials. He says selecting trial sites outside of the US to enrol tens of thousands of patients can result in hundred of millions of dollars in savings. Furthermore, “some also argue that clinical trials conducted outside of the US today are of higher quality because of better adherence to trial protocols and better patient follow-up,” he says.
However, despite this way of working generating a heap of benefits, it still comes with challenges. Madussi notes that despite co-ordinated efforts across different regions to find more common regulatory ground to improve the globalisation of trials, this isn’t always the case everywhere, which can be challenging. “Clearer, shared guidelines between established clinical trial markets have helped enable smoother drug development processes but this is still absent in emerging markets, with considerable regional variation,” he says. “For example, China has become a much more attractive market for sponsors but finding the right partners to help ensure availability of materials or compliance with local regulations can be challenging. Having a clear understanding of local requirements and regulations as they change and evolve can be a daunting task.”
Hebenstreit agrees, saying the globalisation of clinical trials has multiplied the operational and strategic obstacles that clinical trial professionals must circumvent. “In addition to inexperience in conducting trials and differing quality standards, there are widespread differences from country to country in customs knowledge, experience and laws… and there is often the need to manage logistics complicated by countries with limited infrastructure or managing temperature-sensitive biologics, especially outside major cities [where suitable infrastructure and facilities are not always available].”
According to Cutler, the new opportunities in clinical trials also represent its challenges. He mentions advances in genetics and the human genome, which have led to scientific discoveries focusing on subtypes of patients that have certain diseases. “The science is driving us to find specific patients but it has also made the search for those patients more challenging. While there are tools out there to find these patients, applying those tools in the current environment remains challenging,” he says. Indeed, a recent ICON whitepaper that surveyed pharma executives – titled: ‘Improving Pharma R&D Efficiency: The Case for a Holistic Approach to Transforming Clinical Trials’ – revealed that 56% of pharma execs believed patient enrolment was the biggest challenge when conducting clinical trials.
Going global is one solution to find these patients, but even this can be problematic, says Clare Grace, vice president site and patient access at Syneos Health. “There is more competition for patients than there ever has been… driven by the very healthy pipeline and the increasing segmentation of patient populations, which is reducing the pool of patients available to participate in these studies… The competition for patients is unprecedented and the gap in supply and demand is growing every day.” She says a look at Clinicaltrials.gov shows that more than 57 million patients are needed for the studies listed on the site – almost the entire population of the UK.
Regulation issues
The issue around patient recruitment isn’t the only challenge affecting the global clinical trials environment. Cutler says there are also problems with the regulatory environment, which hasn’t kept up with the technology and data available to run clinical trials. He points to ethics approval as a case in point. Here, many clinical trials have to be approved by ethics boards at each individual site around the world, which can take six weeks, and sometimes longer. “That costs time and money,” he says. “There are probably better ways of doing this, especially in the age of artificial intelligence and new technology. Of course, we still need oversight, but I don’t believe we need to be as bureaucratic and local in that sort of approach.”
He also draws attention to protocol amendments, each of which have to be reapproved by ethics committees, which can slow up the trial and add costs. And then there is just getting sites contracted and approved for patient recruitment, which can take up to nine months. Cutler describes this is a “ridiculous amount of time” and calls on governments and regulators to update and streamline the systems, adding that this would be good for both countries and patients.
For Cutler, the concern is the ballooning cost of developing drugs. The longer clinical trials take, he says, the costlier development becomes. The cost implications are something Madussi touches on as well. “From a financial standpoint, the cost of drugs is rising and the budget for clinical supplies is an increasingly large component within the overall cost of the study,” he says. “Medical teams prepare a certain study, selecting a precise standard of care without often realising the implication from a cost perspective.” In addition, the increasing complexity of trials for complex treatments designed to be tailored to individual patients is another factor that can whack up the cost.
Cutler also says Europe’s General Data Protection Regulation (GDPR) is another clinical trial cost because the regulation potentially makes it harder to use data analytics. While he says GDPR is good for patient privacy, he adds that society needs to be aware of its unintended consequences and what this might mean for clinical research. “It’s still early days but over the next couple of years there must be an opportunity to discuss areas of it that represent the cost to patients.”
Brexit and beyond
Another potential challenge is Brexit. With the global nature of clinical trials, there are some question marks over ensuring there are the staff to run trials once the UK leaves the European Union, as well as question marks over the import of clinical trial supplies and the export of samples, not to mention the future impact on research collaborations between the UK and Europe.
Madussi says there is a risk of immediate disruption to clinical trial supply chains – according to the ABPI, 70% of all investigational medicinal products in ongoing EU trials are QP (qualified person) released from the UK – and he is concerned about the future of the UK clinical trial market if Britain is left out of arrangements that could affect the regional and global nature of clinical trials, such as the forthcoming Clinical Trials Regulation (CTR). Hebenstreit, too, believes there will be some consequences. “Post-Brexit, life science researchers and clinical trial sponsors may have to navigate two sets of regulatory guidelines when sharing reagents and expertise between the UK and Europe, potentially increasing study timelines and driving up costs. However,” he adds, “the real impact remains to be clarified”.
The challenges around conducting clinical trials globally can produce headaches but there are ways the landscape could be improved. Cutler mentions proposals by the British government that are up for discussion regarding a standardised and streamlined network of high-throughput clinical trial sites. “That’s the sort of thing we would welcome,” Cutler says. “Large sites with access to large patient populations with a standard approach to ethics approval and contracting – that’s exactly what the industry needs and what would be beneficial for the country.”
Technology too could play a massive role in addressing challenges. Hebenstreit believes pharma needs to drive new digital health initiatives into clinical operational execution. For example, leveraging compliance apps, clinical endpoint and data capture tools, and remote trial delivery systems. He notes that many firms must also strive to launch digital health data collection studies to validate objective measures in quite a few medical conditions.
Meanwhile, Grace explains that technology could offset the challenges surrounding patient enrolment where trials place a burden on patients who may have full-time jobs or other time constraints. For instance, technology could help clinical trials become integrated into the care continuum and accessible to all people. She points to the Salford Lung Studies, sponsored by GlaxoSmithKline, as a case in point. “If we can take research to the patient and enable patients to participate more seamlessly through technologies like telehealth, wearables (or clinical grade sensors) and Skype technologies, we are much more able to include a larger proportion of the population in clinical studies.” In addition, creating awareness of clinical trials is also needed to boost participation rates. “Effective outreach to patients and designing studies that patients are actually able to participate in is key.”
Cutler agrees, noting that, currently, just 3-5% of people are involved in clinical trials. He believes that percentage could get up to 25% over the next 10-20 years through the use of data technology and electronic health records, which would improve direct access to patients. “Going forward, connecting directly with patients makes sites less of a bottleneck. That change, through wearables and virtual clinical trials, will be exciting and will help make us more efficient. If we can get serious about being efficient and realign the regulatory environment there is scope to develop drugs faster and more efficiently for less money.”
That said, Madussi notes that implementing technologies in the pharma industry can be challenging in and of itself. “Stakeholders need to find ways to explore the benefits of technological advancement within a secure framework so that improvements can be developed without posing a risk to patient safety,” he says.
Change might not happen overnight but Grace expects a huge shift in the running of trials over the next decade centred on telemedicine. Cutler, too, believes regulations will eventually catch up and envisages a landscape where wearables, real-world data and virtual trials will be commonplace. Meanwhile, Hebenstreit adds that patients will increasingly drive trial design over the coming years, as well as provide insight on the use of digital in clinical trials. This will also be alongside new and innovative ways of viewing risk analytics, new perspectives on key performance indicators and key risk indicators, enhancements in quality, and improvements in vendor oversight communication, efficiency and performance.
Katrina Megget is a freelance journalist specialising in the pharmaceutical industry
