Featured Viewpoint: eCROs
eCROs: Delivering the next generation of technology and services for the biopharmaceutical industry
||Mark A. Goldberg, M.D.
Chief Operating Officer
The global biopharmaceutical industry faces a daunting array of challenges: intense competitive pressure to bring innovative compounds to market more quickly; rapidly rising development costs; a high rate of failure for pivotal clinical trials; and the exponential growth of study-related data to meet expanding regulatory requirements. In this difficult environment, biopharmaceutical companies must continue to find new ways to improve the efficiency of every part of the drug development process, including regulatory strategy, investigator selection, trial site initiation, patient recruitment, trial monitoring, clinical and drug supply logistics, data collection, data analysis, and the submission of regulatory documentation. Most important, sponsors need to make earlier – and more informed – decisions about their development portfolio in order to improve the success rate of products reaching later-stage trials.
Although eClinical technologies such as Electronic Data Collection (EDC), Clinical Trial Management Systems (CTMS), and Integrated Voice/Web Response Systems (IVRS) have delivered dramatic improvements in trial productivity and data accuracy in recent years, the biopharmaceutical industry must move beyond the gains provided by these individual systems if they are to achieve the cost and time savings that are essential for their future success. The next level of clinical technology requires widespread use of integrated technology throughout the clinical enterprise – combined with innovative clinical services – to create a new operating model that increases efficiency across the development spectrum. This combination of advanced technology and expert services is essential to support the key trends that will characterize clinical development over the next five to ten years, such as:
- Increasing emphasis on early-phase testing to better predict product safety and efficacy – also known as the “Learn and Confirm” model of drug development
- Larger, and more complex, multinational Phase III trials that require global technology and resources
- More expansive Phase IV trials to accommodate growing regulatory requirements for data on long-term product safety, comparative effectiveness research and reimbursement strategies.
Because this next stage of operational improvement requires not only advanced technology but also clinical expertise and global resources, some in the industry have begun using the term “eCRO” to distinguish the capabilities a service provider must have to meet the needs of the biopharmaceutical industry under this new operating model. Although the term may be a bit vague, the concept is clear: eCROs have the resources to provide a broad range of clinical development services that are fully enabled by technology. By leveraging the best available technologies and combining them with clinical experience and a global infrastructure, eCROs would be able to marshal all the necessary resources to help a biopharmaceutical company reduce the time and cost of clinical development at every stage of the product lifecycle.
Supporting early-phase studies –There is an increasing emphasis on Proof of Concept (POC) studies and other early-phase research designed to find signals of a product’s efficacy against a targeted indication as soon as possible in the development process. This new drug development paradigm, often called the “Learn and Confirm” model, relies on sophisticated early-phase testing to provide predictive data that helps sponsors more quickly and accurately select drug candidates with the greatest chances for success in later-stage trials.
Advanced eClinical technologies are essential to the success of the “Learn and Confirm” testing model. For example, adaptive trial designs – supported by real-time data gathering using EDC, ePRO, or IVR/IWR systems – are being used in early-phase studies to change treatment allocation ratios or drop certain treatment arms based on current patients' responses. This approach provides a better chance of identifying the optimal dose during early-phase testing by facilitating the investigation of more doses without substantially increasing sample size. It also helps accelerate drug development by opening the possibilities of seamless transition from Phase II dose-finding into Phase III trials.
Positron-emission tomography (PET) scanning is another important technology supporting the “Learn and Confirm” approach in early-phase trials. In a recent test of a novel treatment for solid tumors, for example, the ability of PET scans to pinpoint tumor shrinkage enabled the sponsor to more quickly confirm proof of concept – supporting a decision to immediately advance the drug into Phase II trials. The technology saved time and money for the sponsor, and accelerated the development of a potentially life-saving therapy.
A well-qualified eCRO must have expertise across the full range of these tools to support this new approach to drug development, as well as experience using these technologies in early-stage trials. The eCRO also must be able to combine the technology with therapeutic area knowledge to select and apply the right technologies for the targeted indication and patient population. The proper application of “Learn and Confirm” in the early stages of drug development could dramatically reduce the cost of drug development by significantly improving the success rate of products in Phase III trials.
Leveraging technology and expertise for global Phase II/III trials – As clinical trials continue to grow in complexity and global scope, the challenges of conducting and managing the numerous sites, organizations, and data systems involved in these larger trials are increasing dramatically. Multinational Phase III trials require both global clinical resources and robust technology to recruit patients efficiently, initiate sites quickly, collect and clean data, and provide cost-effective study management. As a result, a capable eCRO must have a broad array of specialized knowledge and infrastructure, such as in-depth therapeutic-area expertise, clinical trial experience, global patient and investigator resources, and regulatory knowledge. In addition, the eCRO should be able to provide a full range of eClinical technologies – not only the basic eClinical systems such as EDC, CTMS, and IVRS, but also predictive patient recruitment modeling systems, adaptive trial technology, medical imaging, and global collaboration tools.
Cost reductions can be achieved by allowing some clinical functions to be performed in lower-cost regions of the world. These technologies also support “follow the sun” efficiencies – allowing the eCRO to maintain a flexible global workforce that can perform clinical functions, data analysis, and other time-sensitive development tasks 24 hours a day to maximize efficiency and accelerate trial schedules.
Meeting the needs of expanded peri- and post-approval trials – Peri- and post-approval studies (Phases IIIb and IV) constitute another rapidly expanding segment of clinical research. Regulatory agencies around the world are requiring additional data about the long-term safety and side effects of new products when they are used by larger numbers of patients in real-world settings. Healthcare providers – and those who pay for healthcare – are demanding clinical evidence that new therapies provide better outcomes or greater value than existing standards of care. To meet those growing data requirements, biopharmaceutical companies need a wider range of product and safety information that is not available from most Phase III trials. A typical Phase IIIb/IV study presents challenges beyond those experienced by researchers conducting earlier-stage trials – the most significant being the need to enroll substantially larger numbers of patients. A Phase IV safety or marketing study may involve thousands of patients at many hundreds of sites. Given the size and scope of most late-phase studies, greater efficiency in logistics, recruitment, site operations, and information processing is absolutely essential to control costs and handle the huge volume of data. An experienced eCRO will have the global resources and technologies to manage these large trials efficiently and cost-effectively.
Another Phase IV challenge for eCROs is the fact these studies usually include a larger and more diverse range of physicians, including practicing physicians who may have little or no prior experience with clinical trial protocols or technologies. An eCRO must be able to supply technology that is flexible enough to handle multiple languages, simple enough to accommodate people with a wide range of technological expertise, and compatible with the normal processes at the study sites. At the same time, the systems must be sophisticated enough to provide timely, accurate information and support robust security.
Clients are becoming more focused on receiving a comprehensive solution, and less prescriptive regarding the technologies that are used to deliver that solution. Biopharmaceutical companies will increasingly rely on their strategic eCRO partners for complete solutions that combine the right technologies, services, and expertise to deliver the required result. This paradigm shift will also allow biopharmaceutical companies to concentrate their time and resources on core competencies and key tasks like research, product acquisition, and market expansion.
Whether you call them eCROs, biopharmaceutical service providers, or strategic development partners, the companies with the right combination of technology, clinical resources, and development expertise will be delivering development solutions that help biopharmaceutical companies around the world reach their goals in the global marketplace in the years ahead.