For years, the industry has been grumbling about clinical trials – the burgeoning costs, the struggles of patient recruitment, the high attrition rates. Back in 2005, a UK Clinical Research Collaboration (UKCRC) report highlighted that in the UK, delays in trial start-up and recruitment, poor reliability and high costs were putting the clinical research environment at risk. Indeed, competition from other countries saw clinical research in the UK decline from 2005, with the lowest number of applications for clinical trials in 2010. Although the Association of the British Pharmaceutical Industry (ABPI) says numbers have been increasing since that low point, general complaints about efficiency have continued.
And the UK isn’t alone when it comes to the unwieldy clinical trial quagmire. In October, the US-based National Academy of Medicine published a leadership article claiming that “biopharmaceutical development faces an efficiency crisis”. The organisation noted the growing gap in efficiency, with skyrocketing development costs and lagging productivity, making inefficiency “rife” across the board. “Without a substantial increase in the rate of clinical success and subsequent drug approvals,” the Academy wrote, “many observers believe innovators will be unable to bring forward enough new medicines to sustain investment in research and development activities.”
The body, which has called for the harmonisation of standards for clinical trial sites, listed some of the shocking statistics – 11 percent of sites in a given multicentre trial fail to enrol a single patient; 37 percent of sites do not meet enrolment targets; the vast majority of studies are lengthened, often doubling the original time, just to satisfy enrolment targets; and drug development costs double every nine years. In 2015, the Tufts Center for the Study of Drug Development claimed just 11.3 percent of drugs entering clinical testing are likely to be approved in the US. A decade ago, companies could expect a 16.4 percent success rate. Meanwhile, the average clinical phase duration is 6.8 years, an increase of 15 percent over ten years. And perhaps most shocking of all, it now costs a whopping $2.6 billion to bring a single drug to market, the experts at Tufts say.
“Tufts CSDD research has demonstrated that the rising cost and duration of drug development activity are a function of increasing protocol design complexity,” the whitepaper on the topic said. “The average number of procedures per protocol, average number of eligibility criteria, average number of investigative sites and countries where clinical trials are conducted simultaneously, have all increased dramatically during the past ten years creating more demanding protocols both scientifically and operationally.” In addition, the challenges around patient recruitment have made clinical trials something of an efficiency nightmare.
Traditionally, pharma companies have tended to look to clinical research organisations (CROs) and outsourcing as a means to improving clinical trial efficiencies. While this has become a booming industry, it still, however, has struggled to bring efficiencies in line. The recent CRO Oversight Benchmark Survey by Comprehend is a case in point – 90 percent of pharma sponsors plan to increase their use of CROs within the next year but only 22 percent are confident the CROs will hit milestones on time with a quality result.
Tipping point
In many ways, the industry has reached a tipping point and it is waking up to the idea of actively seeking out efficiencies in research and development. A report last year by Accenture, which interviewed 76 US and EU R&D leaders, found that 49 percent believed transforming the R&D model to be more patient-outcome focused should be among the top three priorities for the industry. Other top priorities included faster time to market from first-in-human to approval, and improving R&D productivity via increased quantity and quality of new molecular entities, noted by 36 percent in each case.
Indeed, Tufts has found that pharma is starting to adapt to improve efficiencies, including more target validation to identify and select the most promising drug candidates, and enhancing IT infrastructure to allow for real-world data capture and analysis, which could streamline several aspects of the drug development process.
Dr Sheuli Porkess, executive director of research, medical and innovation, at the ABPI says the industry is evolving to meet the new demands presented by more complex drugs. “There are a number of ways clinical trials can be made more efficient and these are being pioneered throughout the industry, CROs and research partners. This includes looking at approval and set-up processes, innovative clinical trial design and clinical trial simulation adoption, such as studying the effects of a drug in virtual patient populations using mathematical models that incorporate information on physiological systems.”
Trial design is certainly one area getting a makeover. The American Society of Clinical Oncology has previously noted the increasing adoption of novel trial designs, specifically basket (one drug against a variety of diseases, often with a common mutation or mode of action), umbrella (multiple targeted medicines based on the molecular mechanism of a particular disease), and adaptive enrichment strategies (allowing for selection of patients with a particular molecular feature during the trial that is predictive of benefit of the tested drug). “Enrichment, umbrella and basket trial designs are gaining popularity as they present novel strategies to accelerate the drug development process so that the right therapies can be delivered to the right patients quickly,” the organisation said.
In a recent opinion piece, Paul Sabbatini, deputy physician-in-chief for clinical research at Memorial Sloan Kettering Cancer Center, said the traditional “rigid” clinical trial paradigm was “outmoded”. “We are essentially moving toward smaller and smarter trials looking for clearly meaningful improvements. This allows us to evaluate strategies faster and, most importantly, increase the chance of benefit for individual patients. When a clinical trial is well designed – whether the results are positive or negative – we learn important next steps. In addition, if we can match the right patient to the right trial, the number of successful approaches will continue to rise.”
Go digital
That said, patient recruitment has been a bugbear for the industry. But alongside new trial designs are new technologies and digital innovations that can increase patient engagement and streamline the recruitment and start-up process. For instance, social media can improve engagement with patient communities, while wearable devices can help select patients for enrolment, allow patients to conveniently interface with clinical trials, and capture objective real-time data. Electronic medical records can also aid the recruitment process – indeed ICON has partnered with IBM Watson and the Electronic Health Records for Clinical Research project for exactly that reason.
Meanwhile, Janssen is developing its own mobile smart technology called iSTEP (Integrated Smart Trial & Engagement Platform), which registers and tracks medication activities via a scanner linked to an online data portal, and includes electronic smart packaging and blister packs, and an interactive smartphone app for patients. The firm plans to pilot the platform in one of its clinical trials by the end of the year.
However, not all companies are embracing digital. The Accenture report that surveyed R&D leaders found many firms were not fully exploring – and some were even missing – the opportunities presented by digital platforms. Only 38 percent of respondents ranked the use of external health data such as patient records in clinical trials, just 32 percent ranked social media for patient recruitment, with the same percentage classing wearable devices and mobile as important in R&D, and only 22 percent thought digitally enhanced remote trials were the way forward. “These results raise a number of questions about whether companies’ ability to effectively use digital matches their commitment to do so,” Accenture said.
The way forward
Digital and evolved clinical trial design aren’t the only things looking to streamline the drug development process. Increasingly collaborative efforts, data sharing and analytics, and integrating real-world data are becoming more common. This can create a more holistic view of patients and diseases, enhance patient engagement, shape product and trial design, reduce redundancy and duplicity, improve decision-making and efficiency, and ultimately improve outcomes.
Dr Porkess says the British industry is actively collaborating with various parties, including the NHS, to make trials more efficient and is “championing the use of real-world data” in achieving that. “Our members are already using big data to improve clinical trial recruitment efficiency, to provide real-time clinical monitoring, and now we can start to think about using big data for outcome prediction in clinical trials,” she says. “Expanding the use of big data and addressing those long-standing issues that exist with clinical trials efficiency, are both tangible ways we can see the clinical trials landscape change into the future.”
As science advances and treatments become more complex, so too must clinical trials become more efficient. The industry is waking up to this fact. “Looking to the future,” says Dr Porkess, “supporting the development and application of innovative clinical trial designs can help us become more successful and more efficient.”
Clinical trials and Brexit
The EU has been reviewing clinical trials regulation for several years after complaints the EU Clinical Trials Directive was creating too much red tape and excessive cost. In 2014 the EU Clinical Trials Regulation was adopted with the aim to reduce the bureaucratic burden and cost of running multi-country trials in Europe. However, there have been delays with the implementation of the regulation, namely the online portal and database, which has now been pushed back to the second half of 2019. Christiane Abouzeid, head of regulatory affairs at the BioIndustry Association, says the delay means the regulation will not be covered by the Brexit EU Withdrawal Bill currently going through parliament, meaning UK future alignment with the Clinical Trials Regulations will be subject to Brexit negotiations. It is currently unclear to what extent the UK will continue to share clinical trial databases with Europe.
“The UK benefits from a common regulatory framework and market with the EU. The BIA has mounted a strong campaign to represent the interests of its members following the result of the EU referendum. By joining forces with other stakeholders from across the UK life sciences sector, the BIA has made significant headway in ensuring the UK government recognises the importance of maintaining regulatory co-operation post Brexit to ensure the future health and wealth of patients and businesses in the UK and Europe,” she says.
Katrina Megget is a freelance journalist specialising in the pharmaceutical industry
