American Pharmaceutical Review, April 2016

Over the last few years, the complexity, size, length and globalization of clinical trials have continued to grow — in parallel with soaring trial costs. We know that the estimated average cost of bringing a drug to market in the U.S. is about $2.6 billion,1 and the largest portion of drug development cost is for human clinical trials; particularly for Phase III trials, the most crucial and time-consuming phase.

As drug development costs and complexity spiral, sponsors continue to face mounting pressures from regulatory agencies, the medical community, insurers and the public to reduce these costs while improving development time, expanding pipelines, improving drug quality and safety, and meeting more stringent regulatory expectations. As part of the solution, they are increasingly relying on contract research organizations (CROs). Can outsourcing clinical trials to CROs lower the costs of drug development and bringing new medicines to market more quickly? Absolutely. What methods and innovations are CROs adopting to improve trial cost and time efficiencies?

Outsourcing Clinical Trials: A Growing Trend for Cost-Saving

According to the 2016 Nice Insight Contract Research - Preclinical and Clinical Survey,2 there was a big jump in expenditure for outsourcing services this year, maintaining the continuously escalating spend over the last five years. The majority of companies (38%) now spend $51 million to $100 million for outsourcing, and another 18% spend more than $100 million. That is a big increase from the previous year’s Nice Insight survey, where the vast majority (64%) spent $10 million to $50 million on outsourcing and only 23% spent more than $50 million.

Rising costs and falling productivity, among other trends, are driving industry companies to outsource an increasing range of functions to CROs to achieve cost savings. In addition to providing substantial global capacity to drug developers, CROs have become a critical contributor to clinical trial programs. According to a recent report by ResearchandMarkets, clinical trials conducted by CROs are completed up to 30% more quickly than those conducted in-house by pharma companies.3 That, of course, translates into a considerable cost savings and likely a faster market launch.

Pharmaceutical and biotechnology company service needs have shifted, with changes in disease focus, pipelines, technologies and industry requirements1. Typically, CROs stay ahead of the game, fortifying their scientific, technical and regulatory expertise to meet these new industry needs and favorably compete. These changes, for example, call for a deep understanding of growing areas such as biologics and specialized medicine, advanced technologies and knowledge of the latest global regulations. Since it is faster and more economical to outsource these needs to high quality CROs, rather than build the infrastructure and expertise in-house, industry companies are relying more heavily than ever on contract services.

What Clinical Trial Services Are in Greatest Demand?

The level of CRO engagement at every clinical phase has increased, although pharmaceutical and biotechnology companies are relying more heavily on outsourcing for the early phases of clinical research, from drug discovery through Phases I and II. Now nearly two thirds (63%) of companies engage contract development and manufacturing organizations (CDMOs) and CROs for Phase II studies, a big jump from last year, when only 42% of companies engaged outsourcing partners for this phase. Emerging companies outsource 55% of services during Phase I, and 69% of midsize pharma and biotech companies outsource during Phase II.2

Until this year, the services outsourced the most were preclinical, which rose to 60% last year and now dropped to 51%. However, emerging pharma and biotech companies outsource approximately half of their preclinical services, particularly clinical trial design and trial recruiting services.

The Nice Insight survey also indicates that all types of companies acquire or plan to acquire 80% of preclinical trial services and 76% of clinical trial services from CROs for research and development. For preclinical services, most companies outsource or plan to acquire bioanalytical testing (53%), analytical testing (49%), and chemistry and stability testing (48%). The majority of emerging companies (63%) outsource or plan to acquire chemistry and stability testing.

Optimized Site Selection and Recruitment

Industry companies rely heavily on CROs that are knowledgeable about selecting the best global sites with the specific requirements of their clinical trials. Typically, they choose CROs with extensive global clinical trial experience and expertise in their therapeutic area. With an escalating number of clinical trials today driving fierce competition to secure trial sites, more-experienced service providers have worked with more sites and know their capabilities and investigators. CROs also face strong competition for patients in certain therapeutic areas, and must have the expertise to manage increasingly complex trial protocols and increased regulatory requirements.

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CROs that have many years of experience in conducting trials at many global sites are best able to efficiently compete for the optimal trial sites and recruit investigators they worked with previously. The best CROs have relationships with the top physicians in a therapeutic area. These physicians are experienced in running clinical trials and have patients interested in participating.

The cost and time to secure well-qualified sites and enroll patients has soared. Research from the Tufts Center for the Study of Drug Development indicates that it takes eight months, on average, to move from pre-visit through site initiation.4 The basic requirements for making site selection and recruitment more efficient are a combination of selecting high-quality, high-performing sites on a global landscape; using the latest technologies, such as cloud-based solutions; and identifying efficiencies.

Other benefits of outsourcing trials are that CROs can provide expertise in the specific targeted therapeutic area, knowledge of countryspecific regulations, and easier access to patient populations outside the U.S. CROs with regional offices in countries that have a trial’s specified patient populations can provide access to cultural expertise, local regulatory knowledge, and easier access to subjects in that country.5

Effective Big Data Management

Most drug development companies seek data management services through all phases of clinical development. With more sources than ever before contributing to the clinical trial data and costs - more research sites, labs, subjects, procedures, etc., the efficient management of massive amounts of trial data is more critical than ever.

More than half of companies that outsource to CROs expect they will achieve reductions in project lengths and costs by using CROs that employ cloud-based systems, according to Nice Insight’s 2015 pharmaceutical and biotechnology outsourcing survey.6 One way cloud platforms save costs is through centralized biological sample and medical imaging management.

Many high quality CROs utilize e-clinical technologies that provide integration of data from many sources, real-time easy access to data, as well as Web-based tools and social media. Sponsors are increasingly partnering with CROs that have strong digital capabilities to help them quickly elicit key information from mass data that will enable them to make informed, data-driven decisions while reducing trial costs and time.

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New-generation technologies such as cloud-based, fully integrated clinical trial management systems enable greater collaboration and compliance as well as more cost-effective, rapid data delivery, driving time- and cost-savings by reducing the complexities of managing trial data. Sponsors seeking a CRO should look for one with an optimal technology solution, such as a single, easy-to-use data source.

Leveraging Innovation

Partnering with a CRO that ranks high in productivity and innovation can add value and reduce costs in the early stages of development, as well as help improve preclinical throughput. An estimated 10 percent improvement in predicting failure before initiating clinical trials could save upwards of $100 million in costs associated with drug development.7

By strategically partnering with CROs, sponsors benefit from learningcurve efficiencies, economies of scale, and newer methods of rapidly reaching a proof concept - all of which can save costs. Concepts such as risk-based monitoring (RBM) and adaptive clinical trials, as well as newer methods such as computer simulation have emerged over the past decade as more efficient, cost-saving ways to improve clinical trials and process trial data. The advantages of RBM and adaptive trials are reducing the risks in later-stage development, particularly Phase III failures, which are very costly, and making “go/no go” decisions earlier.

Risk-Based Monitoring

Monitoring is typically the most costly aspect of clinical trials, with on-site monitoring comprising 25 to 30 percent of the overall cost of clinical trials. RBM, which has been encouraged by regulatory authorities, has emerged over the last decade as a way to reduce the monitoring expense. Proponents of RBM project that the investment will return a reduction in this expense of 15 to 20 percent.8

A CRO that specializes in RBM can help identify and define study risks and be able to implement an appropriate risk-management strategy that achieves greater efficiencies over traditional monitoring and can save significant costs. These outsourcing companies leverage technology with remote data capture and clinical trial monitoring systems that help monitor specific sets of data for source-document verification (SDV). They also utilize RBM for targeted monitoring to reduce the amount of SDV, based on risk assessment. In addition, through electronic data collection, the systems reduce errors and expedite results. Nice Insight research has shown CROs that offer data management services score above the benchmark for regulatory compliance and productivity.

Adaptive Trials

Adaptive trials use accumulating data to decide how to modify aspects of the study – such as dosage, subject population and sample size – or statistical procedures as a trial progresses, making it more flexible. These trial designs can lead to launching trials with fewer patients, and allow sites to participate in trial design, adapting to their patient population and areas of expertise. The purpose of an adaptive trial design is to objectively use study data to make valid scientific changes to allow a shorter time and less costly path to achieve the study objective, as well as to make the trial more flexible and efficient without undermining its validity and integrity.

Outsourcing to full service CROs with advanced technology can reduce operational costs through global coverage, local support, and innovative software tools to accelerate workflows. Regional CROs help ensure rapid start-up and close monitoring at lower expense.

References

  1. Tufts Center for the Study of Drug Development, 2014. Accessible at: http://csdd.tufts.edu/news/complete_story/pr_tufts_csdd_2014_cost_study
  2. Nice Insight 2016 Contract Research - Preclinical and Clinical Survey
  3. “The CRO Market Outlook: Emerging Markets, Leading Players and Future Trends.” Research and Markets. Accessible at:http://www.researchandmarkets.com/reports/541346/the_cro_market_outlook_emerging_markets_leading.pdf
  4. Getz, K.A., “Uncovering the drivers of R&D costs. 2015 presentation citing data from the Tufts Center for the Study of Drug Development. Accessible at: http://www.clinicalleader. com/doc/the-need-for-speed-in-study-startup-0001
  5. Kasper P., “Meeting the Challenges in Outsourcing Clinical Research to Contract Research Organizations. Monitor, June 2012. Accessible at: http://www.pkasperassociates.com/ pdfs/Final-Monitor-Article-June-2012_12882-12_Kasper.pdf
  6. Nice Insight 2015 Pharmaceutical and Biotechnology Outsourcing Survey, January 2015.
  7. Allen J., et al, “Drugs of the Future,” 2010(7): 67-75. Accessible at: https://www.smr.org.uk/ smr/Archive/PastMeetings/Downloads/SMR_Sept_09_Report.pdf
  8. Ray S., “Clinical Teams Should Re-Think Risk-Based Monitoring Costs to Improve Their Bottom Line. Cutting Edge Information, 2013. Accessible at: http://www.cuttingedgeinfo.com/2013/risk-based-monitoring-costs/