Managing Clinical Trials in Emerging Markets
In emerging markets, by contrast, there are few standard processes for regulatory activities. Companies have attempted a variety of approaches to expand and integrate regulatory activities with global clinical trials. Large biopharma companies typically establish local infrastructure in a given market through organic growth or acquisition. Smaller companies typically secure local regulatory and safety support as part of a "full-service" model through a CRO.
The "full service" outsourcing model that Amgen traditionally employed generally entails contracting the CRO to complete the full clinical trial and provide the final results. This includes regulatory filings, patient recruitment, site management, safety reporting, and data management—an end-to-end package. Over the years, each of these functions has become more specialized and sophisticated. Contrary to conventional wisdom, full-service CROs have not developed the capability or capacity to provide true full service and often do not have integrated global coverage. Instead there has been a rise of CROs with country or regional expertise or even with a focus on a particular therapeutic area. As a way to compensate for this lack of full global reach, companies rely on a network of regional or disease-specializing CROs, especially in emerging markets. It is not uncommon that these subcontractors further outsource to others, thus introducing variability in the quality of services. This can lead to a substantial risk to the sponsoring companies, as the sponsors become further removed from the actual execution of clinical trials and coordination with the local health authorities in the emerging markets.
All services in a full-service outsourcing model are bundled, so the model also diminishes a company's flexibility to adjust a particular service that is not working well (for example, late approvals of applications, poor relationships with regulatory agencies, inefficient capturing of adverse events information, etc.). This liability is particularly pronounced when executing a low volume of trials. In reality, there are compelling reasons to use the same provider for as many functions as possible, but the option to choose different providers gives a company more control. Ideally, a company that desires to maintain as much control as possible when conducting clinical trials in emerging markets needs the flexibility to choose an array of providers with functional expertise, regional capabilities, therapeutic expertise, regulatory know-how, and local-agency connections.
Evolution of the New Model
Like other drugmakers, Amgen is seeking new markets by clinical and commercial expansion into countries where it currently has no presence. Accordingly, Amgen is using a combination of virtual operating models and strategic partnerships to launch products without increasing its bricks-and-mortar infrastructure. The main driver is not costs (although cost savings are realized) but control of operations, good governance, and patient safety. Because this is a regulated industry, what occurs in clinical trials overseas can have an impact on regulatory filings in the US and in other parts of the world. Poor data quality impacts overall results, thus delaying product approval and access of medicine to patients in need.
Implementing a global functional outsourcing model presented the company with unique challenges. In addition, Amgen's particular model had to be installed in three months to support a wave of major Phase III studies starting up across Latin America, Southeast Asia, and Central Europe, as Amgen was seeking to increase access to patients worldwide who would benefit from its novel therapies.
Amgen put this model into practice without overwhelming investment in human capital. A new role—Regulatory/Safety Liaison—was created at each hub, but most other positions were filled by existing staff, with expanded job descriptions. Amgen hired several new staff members, but this incremental cost was relatively minimal and quickly offset by the advantages of the new hub-and-spoke model.
The primary responsibility of the Regulatory/Safety Liaison is to manage the FSP staff and act as the conduit to relevant functions at Amgen. Leading a virtual team requires a combination of skills—strong technical grounding, effective project management, and clear communication. The manager is accountable for all regulatory/safety activities through FSPs in spoke countries, including ensuring the timeliness and quality of regulatory and safety deliverables in accordance with Standard Operating Procedures (SOPs), Good Clinical Practice (GCP)/International Conference on Harmonization (ICH) guidelines, and local regulations.
After selecting the best partner for each function in each region, Amgen established service agreements to fully document the working relationship and agree on performance metrics regarding safety reporting compliance, clinical trial agreement (CTA) submission and approval cycle time, and passing local validation. The agreements also included parameters for effective communication, escalation, risk management, and budget controls.
Early Results and Lessons Learned
This FSP model provides Amgen with greater control and flexibility than is generally available using traditional CRO outsourcing. More importantly, the hub-and-spoke approach ensures efficient and timely regulatory approval of the clinical trial application for global trials in emerging markets, while ensuring patient safety and compliance. The model has only been deployed since late 2008, yet Amgen is already realizing clear and positive results:
» Seamless support of large and small global clinical trials in new countries;
» Average time savings of approximately two months in CTA submission and approval;
» Close to 100 percent reliability of on-time adverse event submission and periodic report compliance; and
» Improved capacity to bring on, manage, and roll off the highly skilled resources required to support clinical studies
Yet the functional hub-and-spoke model is not without risks and challenges. For example, this model should not be deployed in regions where a company has local infrastructure because doing so creates inefficiencies and overlapping responsibilities.
Accurately forecasting the level of work is another challenge. With the functional service model, budgeting and associated planning must be done using an activity metric (for example, the number of CTAs completed or interactions with health authorities) rather than the aggregate patient number used in the full-service model. An additional difficulty with a hub-and-spoke system is aligning regional clinical and commercial staff. Despite initial attempts at complete alignment, a region-by-region analysis revealed that some regions were better served by a staffing model where clinical and commercial staff were not co-located. The FSP model has been designed primarily to support Amgen's clinical trials. As Amgen is expanding its commercial and clinical footprint in emerging markets, hubs have been created in support of the clinical activities, which do not necessarily represent commercial hubs for Amgen.
The full-service model remains an option, but the functional-service model is maturing and can be beneficial for companies seeking to expand globally with minimal infrastructure investment. The new model offers more operational control and flexibility, is scalable to changing business needs, and allows for brand building in new markets. Critically, implementation has been achieved primarily by redefining job descriptions for existing managers, and the overall setup costs have been quickly amortized through cost savings and effective trials.
Romi Singh is Executive Director, Global Regulatory Affairs & Safety at Amgen. He can be reached at email@example.com
Vitaly Glozman is Director in PRTM's global healthcare practice. He can be reached at firstname.lastname@example.org
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