With clinical trials representing the lion’s share of drug development costs, sponsors are keen to outsource in an effort to control rising costs associated with therapeutic complexities, regulatory demands, and timelines. Outsourcing to CROs is anticipated to grow at a 7.4% compound annual growth rate through 2019, with a market penetration rate of 72% by 2020,1 while a report from The Business Research Company shows the global market for clinical trial services is forecast to grow at 12% year on year to 2021, raising its value to $44.4 billion.
As demand for services intensifies, the CRO industry continues to see consolidation. M&A spending in the CRO industry reached $24 billion in 2016, with the top nine CROs now controlling 60% of the market share in clinical trials.1 Two of the more recent mega-mergers include InVentiv Health and INC Research, now Syneos Health, one of the world’s largest CROs, and Quintiles and IMS Health, now IQVIA, in transactions valued at approximately $7.4 billion and $17.6 billion, respectively. According to a report from The Business Research Company, IQVIA is the largest player in the global CRO market with a 12.4% share, followed by Laboratory Corporation of America Holdings, ICON Plc, PAREXEL and PPD.
David Johnston, Ph.D., executive vice president, Global Clinical Development, PPD, said, “We continue to see consolidation within our industry, both for CROs and big pharma. As the universe of pharma companies gets smaller, CROs will continue to be challenged to position themselves as key strategic partners. These mergers have the potential to offset the rising costs of drug development, which is another important trend the industry faces. However, much of the burden of reducing costs—and the related effort to increase efficiency and shorten timelines—is being placed on the back of innovation and technology.”
In addition to the more conventional reasons of gaining therapeutic expertise and reducing costs and timelines, access to data is a key motivator for outsourcing in today’s market. Dr. Johnston said, “Outsourcing offers the opportunity for biopharmaceutical companies to leverage the specific expertise and broad experience of CRO partners, and also supports efforts to reduce the time and cost of a trial. PPD’s focus is on bending the cost and time curve of drug development by providing our clients with innovative trial delivery models and access to new data sources and solutions that may not be available to them via insourcing. Through PPD’s enterprise relationships with big data sources, integration of workflow management platforms and data analytics platform, we can help our clients decrease the cost of drug development.”
The opportunity to effectively manage, analyze, and gain insights from data is a growing incentive to outsource. According to Chris Smyth, Ph.D., executive vice president, Oncology Division, Novella Clinical, “I believe the key motivator for outsourcing today is access to data. We use our ability to tap into data analytics to inform virtually every facet of the clinical trial. Especially in the case of oncology trials with emerging biotech companies, the access to data and the interpretation of that data plays a crucial role in efficient site selection, optimizing recruitment and even identifying study-eligible patients, which of course, can dramatically improve the chance of success and improved patient outcomes.”
Rise of Orphan Drugs
Just as massive cohorts in clinical trials for drugs to treat the most common diseases can prove difficult, smaller, more precise patient populations create equally challenging obstacles for drug developers. A significant trend impacting CROs and the services they provide is the rise of precision medicine, which is the customization of medical treatments and products being tailored to the individual patient, as well as orphan drugs, defined by the FDA as those intended for the treatment or prevention of rare diseases that affect fewer than 200,000 people in the U.S.
According to Sy Pretorius, senior vice president and chief scientific officer of PAREXEL, “We are seeing more researchers turn to precision medicine and, as a result, CROs are increasingly designing smaller trials in populations that are often more challenging to find and recruit. Related to this, the importance of understanding genomics, biomarkers and companion diagnostic development has never been more significant for CROs.”
Richard Staub, president, Research & Development Solutions, IQVIA, added, “With the rise of precision medicine, there’s an increasing demand for innovative ways to conduct trials more efficiently to help biopharma companies who are faced with the high costs associated with developing more targeted therapies and meeting complex regulatory requirements. And timing is critical in this industry.”
Fueled by the Orphan Drug Development Program, which provides important financial incentives—from funding and tax breaks to seven-year market exclusivity—to encourage pharma and biopharma companies to develop drugs and biologics for rare diseases, this sect has seen a marked uptick in recent years. According to the FDA, the program has enabled the development and marketing of more than 600 drugs and biologics for rare diseases since 1983. Moreover, a record number of personalized medicines were approved by the FDA in 2017, and now account for approximately one in four New Drug Approvals. Nevertheless, these therapies require specific development and regulatory expertise to address the many challenges they present.
Dr. Smyth of Novella Clinical, said, “We know that 40% of orphan designations in Europe2, and greater than one-third in the U.S.3, are for rare cancer treatments. Many common cancers are now treated as rare biomarker-defined diseases falling into orphan designation. While this may not be the ideal approval pathway for targeted molecular treatments, orphan status has incentivized many companies to develop new therapies for rare diseases. This presents an opportunity for us to further engage customers by assisting in navigating the inherent challenges that come along with orphan drug development.”
Nuala Murphy, president, Clinical Research Services, ICON, added, “We expect there to be continued demand for services in the areas of orphan and rare disease drug development as sponsors look for therapeutic knowledge and global site relationships to help them in smarter trial design and to recruit patients faster, based on previous experience in these complex areas.”
Real world evidence is poised to play a growing role in drug development during the next three years, according to a recently completed study conducted by the Tufts Center for the Study of Drug Development, but the availability and cost of acquiring data remain key challenges. As a result, large pharma, biopharma, and CROs plan to increase internal staff dedicated to collection and analysis of real world data by 25% between now and 2020, according to a recent Tufts CSDD survey.
“Across the industry, there is real interest in the value of real-world evidence and other big data sets. These types of data are the foundation for discussions with payers. In addition, CROs and sponsors can potentially leverage this data across the entire drug development value chain to reduce costs and timelines, improve quality, and ultimately, improve the probability of success,” said Mr. Pretorius of PAREXEL.
However, according to recently completed analysis by Tufts CSDD, the growing volume of data collected in clinical trials is contributing to longer development times and posing technical and integration challenges to clinical data management staff. The study found that 77% of sponsors and CROs have difficulty loading data into their primary EDC system due to compatibility, technical demands, and integration challenges. Sponsors and CROs use an average of six applications to support clinical trial activities, and according to the study, protocol changes are the most common reason for delays in building study databases, accounting for 45% of database build delays reported by sponsors and CROs.
Henry Levy, president of Align Clinical CRO and chief strategy officer for Veeva Systems, said, “One of the biggest challenges is that there are different processes and systems across sponsors and CRO partners, making collaboration and real-time decision-making difficult. This will only get more challenging as the ecosystem of stakeholders continues to expand and outsourcing remains a core part of trial strategies. Align Clinical CRO is working to make it easier for the industry to adopt common operational processes and technologies. Open technology standards will remove these collaboration barriers and ensure sponsors and CROs can collaborate and execute trials much more efficiently.”
How are CROs helping to overcome challenges and delays associated with the growing volume of data in clinical trials and expanded use of real world evidence? According to Nuala Murphy, president of Clinical Research Services at ICON, “With the advances in computing power available today, it’s not the amount of data per se that creates the challenge. The challenge is analyzing the types of data, both structured and unstructured and doing it in a way that yields scientifically relevant insights. Organizations require access to the right mix of specialist analytic tools and resources, together with a data strategy that supports interoperability standards in order to integrate the disparate data sources.”
There are several measures CROs can take to effectively manage the inevitable challenges that come up during clinical trials. According to Sy Pretorius of PAREXEL, “These include investing and developing the right infrastructure and technology solutions to capture, process and analyze these oftentimes massive data sets, and developing appropriate and validated processes associated with the generation of real world evidence that are able to withstand ever increasing regulatory, payer and other stakeholder scrutiny.”
Meeting these challenges head on, Richard Staub, president, Research & Development Solutions, IQVIA said, “We see the growing volume of data and real-world evidence as an opportunity to reimagine and develop new approaches to clinical development, speed innovation, and accelerate improvements in healthcare outcomes. We have invested in an unparalleled amount of real-world data and analytics—over 30 petabytes of data, gathered from more than 800,000 unique data sources. But it’s not enough to just have the data. It’s critical to have the right expertise to review and gain actionable insights from them.”
IQVIA’s data scientists are providing advanced analytics of its data through machine learning and predictive modeling to help anticipate challenges before they occur. “To aid our data team, we’ve invested in new technologies that are able to handle translating large-scale data quickly enough to influence decision making in nearly real-time,” said Mr. Staub.
Moreover, once strictly used to monitor post-market safety and adverse events, real-world evidence is now being leveraged to support broader aspects of drug development, including the conduct of clinical trials and regulatory submissions. Eric Faulkner, vice president of Real-world Value and Strategy, Evidera, said, “We have seen patient-centric data shifting from “nice to know” to “got to have.” By opening the door to patient-centric and now real-world evidence, the U.S. FDA is acknowledging the value of understanding benefits and risks reflective of real-world scenarios of care.”
Mr. Faulkner added, “Drug manufacturers are now trying to understand two things: what specific RWE studies should be submitted with a regulatory package, and how that information will be used or has potential to enhance, delay or forestall approval. Despite this uncertainty, the introduction of RWE at the regulatory level offers a significant opportunity to differentiate. Drug manufacturers that do not invest in early RWE may face disadvantages if their evidence package is less compelling than competitors.”
As RWE becomes more and more accepted, it has the potential to overcome some of the limitations inherent in clinical trials. Mr. Faulkner noted, “Early RWE also has the advantage of bridging information gaps relevant to downstream decision-makers (e.g., payers and providers). Clinical trials in some disease areas are changing, making the use of RWE a logical addition to provide flexibility and efficiency, as well as a means to contextualize the benefits and risks of new products in ways difficult to capture in a pivotal study. Such a step also reflects a broader recognition by health stakeholders that evidence development is a continuum and that, while having advantages of internal validity, the traditional clinical trial does have limits and is not the final word on product value.”
Nearly 80% of trials fail to meet enrollment timelines, and these delays can amount to $8 million in lost revenue per day, according to one estimate by Cutting Edge Information.4 Virtual trials, which use technology for patient engagement to collect safety and efficacy data, are emerging as the drug development tool of choice, and offer the potential to disrupt traditional outsourcing and collaboration models. As such, Big Pharma is betting on virtual trials to maximize clinical trial efficiency. For example, Novartis is among the latest to team up with Science 37, a mobile technology and clinical trial company, to enable patients to participate in studies using mobile devices and telemedicine services, joining others including Sanofi and Otsuka.
Mr. Staub of IQVIA said, “For decades, clinical trials have utilized a traditional site-based approach. New approaches that leverage advances in technology, such as virtual clinical trials, have the potential to be more cost effective and patient centric. A virtual clinical trial approach requires in-depth clinical operations and therapeutic expertise, driven by a technology-enabled collaboration across telemedicine, home healthcare, mobile health devices, and other elements. Virtual trials have the potential to reach more patients, enhance patient engagement, and create a more personalized approach that reduces some of the burden on patients. We think this is an exciting development in the industry—for both sponsors and patients alike—as we utilize modern technologies to usher in the future of clinical research.”
The advent of virtual trials and mHealth capabilities are having a significant impact on the clinical trial ecosystem and the traditional ways of conducting trials, according to David Johnston, Ph.D., executive vice president, Global Clinical Development, PPD. “The mHealth approach is helping us create more patient-friendly trials because data can be collected in new ways. The idea is that by making the experience more convenient with less effort required by the patient, that enrollment will be higher and dropouts will be lower. At the same time, these new ways of collecting data gives us access to new patient populations currently not engaged in trials,” Dr. Johnston said.
“The bottom line is that we’re able to collect more and different types of data than ever before, which should lead to quicker decision-making, ultimately speeding up the overall drug development process," Dr. Johnston added. “And, by collecting data remotely, a host of new endpoints is possible. We are now able to access broad streams of data and more frequent intervals of readings.”
With virtual trials offering the potential to execute trials more efficiently than ever before and RWE allowing for more comprehensive data to be applied to product development and beyond, the clinical development landscape may never look the same. Furthermore, with CROs at the very heart of it, we can expect their role in supporting drug development to be ever more critical in the future.
- Chung, Jae 2017 Oct. 23 CRO Consolidation: A Sinister Threat Or Windfall For Pharma? https://www.forbes.com/sites/forbestechcouncil/2017/10/23/cro-consolidation-a-sinister-threat-or-windfall-for-pharma/#2b3b5f906213
- Orphanet Journal of Rare Diseases, 2017 Feb 16. doi: 10.1186/s13023-017-0578-4 https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0578-4
- Oncologist, 2016 Apr. 21 (4):487-93. doi: 10.1634/theoncologist. 2015-0397. Epub 2016 March 28. https://www.ncbi.nlm.nih.gov/pubmed/27022038
- CenterWatch, 2017 March 13 Sanofi bets on virtual clinical trials https://www.centerwatch.com/news-online/2017/03/13/sanofi-bets-virtual-clinical-trials/
Align Clinical CRO is a recently launched life sciences industry standards group that is joining forces with CROs to develop open technology standards to help transform clinical trial operations. The organization brings together six leading CROs to help establish open technology standards aimed at simplifying trial execution and improving the productivity and efficiency of clinical trials for sponsors. Members include Syneos Health, ICON, Medpace, Inc., PPD, PRA Health Sciences, UBC and Veeva.
Henry Levy, president of Align Clinical CRO and chief strategy officer for Veeva Systems, said, “Our mission is to make it easier for the industry to work together during clinical trials. We’ll do that by solving common pre-competitive industry challenges such as sharing operational metrics about trial data during study execution. There was tremendous energy and momentum among leading CROs to come together and make clinical trials more efficient and productive. Align Clinical CRO signals the commitment of CROs, who run a significant percentage of total trials, to find common solutions that benefit the entire industry and improve drug development processes.”
Brett Husselton, senior vice president of commercial strategy at UBC, one of the founding members of Align Clinical CRO, added, “The purpose of Align Clinical CRO is to create open technology standards that make it easier for life sciences companies and CROs to work together. The initiative is pragmatic in that it is assembling full-service outsourced service providers to accomplish three core goals: 1) align on common friction points within the design, implementation, operational, and ongoing management phase of outsourced research; 2) develop standard data definitions and models that will be endorsed by this deep pool of CROs; and 3) make the standards universally available to enable scale, decrease the time wasted on non-strategic activities.”