Just as drug products have become increasingly complex, regulatory and payer demands have added a myriad of complexities and costs to drug development. As a result, data is now valued as the key driver of clinical trials today. Also, strategies behind marketing approval and reimbursement are at the forefront of sponsor demand. As the regulatory landscape evolves, CROs must also adapt to new and changing requirements. To help sponsors navigate increasingly complex trials, regulatory hurdles, and market access concerns, consulting services have become a major part of the CRO service portfolio.

According to recent analysis by the Tufts Center for the Study of Drug Development of the Journal of Health Economics, the average cost to develop and gain marketing approval for a new drug is now estimated to be $2.6 billion. This price tag per approved drug is based on estimated average out-of-pocket expenses of $1.4 billion and time costs of $1.2 billion. Also, the U.S. FDA requires post-approval studies as a condition of approval, and according to Tufts CSDD, these costs of $312 million bring the full product lifecycle cost per drug, on average, to $2.9 billion.

Some factors attributed to higher clinical costs are increased complexity, larger trial sizes, changes in protocol design to include efforts to gather health technology assessment information, and testing on comparator drugs to accommodate payer demands for comparative effectiveness data.

This article will discuss the drug development trends impacting CROs and services and what’s driving outsourcing in today’s market.

Pharma & Biopharma Trends
Among the key pharma/biopharma trends impacting CROs and services resulting in increased outsourcing penetration, are a greater number of drug approvals, along with specialty therapeutics and complex trial protocols, and data-driven insights required for regulatory and commercialization strategies.

According to Mark A. Goldberg, M.D., president and chief operating officer of PAREXEL, “For several years, we have seen growing demand for complex and global studies, and we expect this trend to continue. Additionally, we see increasing outsourcing penetration in areas that were typically outsourced less in the past including medical, such as pharmacovigilance, and regulatory affairs.”

The FDA approved a record 56 new drugs in 2015 with the majority of those approvals within specialty or complex indications, such as rare diseases, oncology, and autoimmune diseases. “The increase in FDA drug approvals is also consistent with the increased demand for outsourcing that we see in these specialty therapeutic areas. Increased approvals also mean that our clients have more products to position for market access and commercialization,” said Dr. Goldberg. “We established our PAREXEL Access group to focus on market access consulting, evidenced-based value demonstration, medical communications, and pharmacovigilance to help companies obtain reimbursement and to support the product throughout its lifecycle.”

As such, these development teams work to help ensure trial designs capture the information ultimately needed to support regulatory approval and reimbursement, and prepare the materials to communicate the findings to payers and health care providers.

Commenting on the impact of R&D trends, John Lewis, senior vice president, Policy & Public Affairs, ACRO, said, “The science is advancing very quickly, especially in areas like immuno-oncology and genetics research. This is very exciting for researchers but also presents challenges to rethink the way clinical trials are being done. Outside of the science, some of the emerging trends are new trial designs like collaborative trials, more emphasis on real world evidence, including data from electronic health records (EHRs) and patient registries, and the incorporation of new technologies into clinical trials, from the use of social media to wearables.” He added that these trends impact biopharma and CRO services, and pose new challenges for the FDA and other regulators.

Among the factors impacting clinical trials are the growth of personalized medicine and increasingly complex trial protocols, which requires innovative approaches to clinical trial execution. As a result, according to Cynthia Verst, PharmD, MS, president of Clinical Operations at Quintiles, “Since 2002, there have been marked increases in the total number of endpoints, eligibility criteria and procedures required in typical Phase II/III studies, as well as increases in the number of countries and investigative sites required in trials. Let’s take oncology for an example. Today, three out of five oncology treatments are targeted therapies, with efficacy in only a small subpopulation of patients.” This presents significant challenges for recruiting patients that fit a particular profile and traditional models for targeting these sub-populations are time- and cost-intensive, according to Ms. Verst, requiring better alternatives.

Quintiles is responding by setting up a dedicated network of oncology centers in an effort to accelerate recruitment efforts. Leveraging a combination of site networking, investigator site-focused technology and process optimization, the company aims to enable pre-identification of patients based on study and biomarker criteria, across broad geographic areas, using EHRs and other secondary data sources.

Opportunities & Investments
According to the executives we spoke with, the biggest opportunities for CROs lie in data-driven insight, development strategies, regulatory consulting, as well as commercialization capabilities. “PPD has developed, implemented and continues to expand clinical monitoring and adaptive and intelligent monitoring strategies, which are integral to the way we conduct clinical trials,” said Niklas Morton, senior vice president of Global Biostatistics, Programming and Medical Writing, and Clinical Innovation Lead, PPD. “Innovation is focused around rapid data integration and advanced analytics capabilities that drive operational excellence and ongoing innovation.”

Also, strategic trial planning, particularly in therapeutically focused areas, is a growing service area for CROs. Rob King, chief operating officer, Novella Clinical said, “With Novella’s focus on oncology development in the small and emerging biopharma sector, we are adding clinical scientists, oncology development strategists and feasibility analysts. This therapeutically focused staff brings value to customers during trial planning by helping to determine optimal trial design and refinement of the feasibility strategy. Novella is also adding staff and technology solutions to decrease the administrative and regulatory burden on our investigative sites.”

The biggest opportunities, according to David Shoemaker, senior vice president R&D at Rho, lie in regulatory consulting in all facets of the product development process including the nonclinical phase in pharmacology/toxicology, CMC, clinical development strategy, and reimbursement strategy. “Also, with the requirement for CDISC compliance kicking in for all clinical studies in December, the end to end strategy employed by Rho for many years is attractive to many clients at the early stage of development,” Mr. Shoemaker added.

As a result of regulatory agencies demanding more data to support new drug approvals, and more evidence that new drugs are safer and more effective than existing products, the complexity of clinical trials and the size of regulatory submissions are driving demand for CRO services.

Dr. Steve Cutler, chief operating officer, ICON plc said, “We will continue to grow our late phase and commercialization capabilities in line with the increased requirement for sponsors to be able to demonstrate the economic value of new treatments. Sponsors need to increasingly generate outcomes data both as part of the product approval submission and as part of post-approval research programs. So there’s a growing opportunity for CROs who can offer support in developing and interpreting outcomes data.” It seems the service industry is positioned well when it comes to regulatory burden and what might be an even more complicated realm, healthcare.

Streamlining Drug Development
In addition to the increased use of technology, efforts to advance drug development and improve the clinical trial process within CRO/Sponsor alliances often include innovative trial designs, such as adaptive and model-based drug development using analytics.  

“At the trial design phase, sponsors and CROs are taking more of a portfolio, rather than a study view, and looking at new clinical trial designs, such as adaptive trials, to help identify promising drug candidates earlier and discontinue the development of drugs that are unlikely to be approved or will have reimbursement challenges,” said Dr. Cutler at ICON.

“CROs and sponsors are also applying new clinical trial techniques, such as risk-based monitoring, to drive further efficiencies by focusing on risk detection, mitigation and the prevention of errors, and looking at activities that have the greatest potential to improve patient safety and data quality. This proactive, early detection and mitigation of risk brings more effective resource deployment, and in our experience, has the potential to reduce monitoring costs by as much as 21%,” added Dr. Cutler.

Also, the increased use of model-based drug development represents another opportunity to streamline drug development. PAREXEL’s Dr. Goldberg said, “We created our Quantitative Clinical Development group to leverage mathematical models for a quantitative analysis of the relationship between drugs, disease and patients. We believe model-based drug development can improve the efficiency of clinical development by providing quantitative justification for trial design, dose selection, and decisions during trial execution.”

Technology has no doubt resulted in countless advances in clinical trials. Today, data is paramount and new ways to extract valuable information is essential to creating trial improvements and efficiencies.

Daniel Burch, M.D., vice president, Therapeutic Area Head, Neuroscience, Global Product Development, PPD, said, “By using technology to allow in-stream data review and analytics during the course of a trial, we can better manage our overall effectiveness, provide operational excellence, continuous improvement, and therapeutic advancement, as well as expanded service offerings. For example, PPD uses its adaptive and enrichment designs, such as sequential parallel comparison design. SPCD—or Trimentum as we’ve branded it—is a trial design aimed at significantly reducing the impact of the placebo effect in clinical trials, particularly in neuroscience indications, helping to enhance the efficiency of our clients’ trials.”

Finally, input from both the Sponsor and CRO is needed if drug development challenges are to be overcome. According to Mr. Lewis at ACRO, “Many of the efforts to streamline development are being done within specific Sponsor/CRO partnerships where there is a great deal of experimentation going on that is not necessarily in the public view yet.” We’ll have to wait and see how these new partnership models unfold. 

At a higher level, ACRO, which works with global industry stakeholders to promote a better and more efficient clinical trial process, launched a CRO Forum last year to provide a CRO perspective on various TransCelerate projects. “This relationship continues to evolve and we are making good progress in some areas of common interest, like risk-based monitoring, site qualification and training and, coming up, eConsent,” Mr. Lewis said.

TransCelerate BioPharma, a non-profit health-based organization, aims to collaborate across the global biopharma R&D community to identify, prioritize, design and facilitate implementation of solutions designed to drive the efficient and high quality delivery of new medicines.

Regulatory Oversight and Transparency
The advancement of regulatory oversight and the associated requirements for increased transparency present new and imminent challenges for the pharma/biopharma industry. How are CROs preparing? According to Elizabeth Madichie, Ph.D., global head of Regulatory Affairs at PPD, “To effectively manage, a significant proportion of this will be outsourced, and CROs need to deliver the required outcomes while realizing efficiencies. PPD is preparing for this in a number of ways: ensuring complete and ongoing understanding of individual country and global requirements and expectations; growing and deploying experienced, globally thinking personnel to drive multi-country strategies and efficiencies; and establishing clear and globally applicable benchmarks and measurements to prove adherence to expectations.”

Mr. Lewis of ACRO, added, “On the regulatory front, the biggest issues for our members are consistency and predictability. We need to be confident that the regulatory pronouncements from the senior people in regulatory agencies penetrate down to all levels so there is predictability. The science and the clinical trial designs and technologies are advancing so quickly that it’s difficult for the regulators to keep up. To the extent to which sponsors and CROs are concerned about regulatory uncertainty in regard to new technologies and trial methodologies, innovation will be slowed. This is a major challenge.”

To prepare, CROs need to ensure that they have strong regulatory capabilities that address both regional and country-specific regulatory requirements, according to Dr. Cutler of ICON plc, “It’s also important that these teams develop close relationships with regulatory agencies and maintain an ongoing dialogue. Having a seat within industry associations such as ACRO also allows CROs input into the regulatory process,” Dr. Cutler added.

The Future CRO
As pharma and biopharma R&D evolves, what will the future CRO model look like and what expertise will be needed? Innovative clinical trial designs, and certainly demand for data-driven insights will continue with new and emerging complexities for regulatory approval and payer reimbursement.

According to Ms. Verst of Quintiles, “In the “CRO of the future,” harnessing newer design approaches and improving data accessibility will ensure that we are helping to generate earlier comprehensive evidence to address the questions and unmet needs of the multiple healthcare ecosystem stakeholders. This same evidence can assist in identifying the right candidates for trials more quickly while ultimately helping to improve patient outcomes.”

Also, as personalized medicine grows, development will be concentrated on smaller patient populations, and, according to Dr. Cutler at ICON, CROs will need to adopt more modern clinical trial designs to help sponsors develop these targeted treatments. He noted that adaptive designs can help identify the sub-population that has the best response rate to a particular drug, or which treatments need to be killed early due to their unlikelihood of being approved or reimbursed.

Technology innovation is playing an increasingly important role in helping to support more efficient drug development. According to Dr. Cutler, “The larger CROs have been at the forefront of this innovation, developing technology solutions that support better trial design (e.g. adaptive trial software) and better integration of trial data from multiple systems. Finding the right mix of in-house capabilities and technology vendor partnerships to help them derive the best insights from clinical trial data is important. CROs will also need to be experienced in designing and interpreting the data from outcomes studies as sponsors are under increasing pressure to demonstrate the economic value of their drugs.”

Meanwhile, CROs are taking on new technology endeavors to keep up with fast changing IT pathways. Mr. Lewis of ACRO said, “We are seeing partnerships emerge between CROs and entities like IBM Watson, Google, Apple, Patients Like Me, 23andMe and other disrupters and technology providers. But as we know, as in other industries, technology by itself cannot solve problems without context and expertise. No one has more expertise in running clinical trials than our members.”

With that said, CROs will also need provide dedicated personnel for services beyond that of the traditional clinical role. “Ultimately the quality of the data incorporated into the marketing application is what is of utmost importance to clients, so the CROs who understand what it takes to submit a quality marketing application will have an advantage in all phases of development, said Mr. Shoemaker at Rho. “CROs will take a longer term view of their relationships with pharma/biopharma companies and provide team members for the life of the development program, not simply a single clinical trial. Consequently, CROs will have to employ individuals who span the entire disciplines of specialties needed for product development including reimbursement and marketing, as some companies will inevitably need different services.”

Finally, beyond meeting current R&D challenges, CROs must position themselves to anticipate sponsor needs and then deliver results. According to Dr. Goldberg of PAREXEL, “The role of the biopharmaceutical services company to innovate and find more efficient ways to bring products to market is going to be absolutely critical. The industry will likely find itself under continued cost pressure; therefore, biopharmaceutical services organizations will be increasingly challenged with helping clients to get products to market as quickly and cost-effectively as possible. Biopharmaceutical services companies must provide strategic leadership for both achieving regulatory approval and market access; this is a challenge we are excited to take on.”

The changing pharma/biopharma R&D landscape has created a lot of opportunity for CROs to provide a multitude of services, not just conducting clinical trials. There is greater interest and need for consulting services and data-driven technologies to accommodate current regulatory and payer demands, as well as dedicated personnel throughout the drug development continuum to help Sponsors bring their products to market.