How Technology Can Aid In The Relationship Between Society, Regulators, And The Life Sciences Industry

By Steve Heath and Tony Hewer

A range of reports over recent years, perhaps in particular those from PWC such as “Pharma 2020: The Vision — Which Path Will You Take,” have highlighted the increasing pressures on the global pharma industry. Reductions in regulatory approvals and new drug applications (NDAs) combined with the impact of patent expiry on key blockbuster molecules present severe commercial pressures.

Responses to these pressures have included megamergers, cost cutting/efficiency gains via outsourcing, partnering with biotechs, and internal organizational change to develop new discovery paradigms and structures. The impact can be severe in terms of job cuts or in development terms as seen, for example, in sanofi-aventis recently slashing 14 drugs in development, including four nearing their final stages.

The clinical development outcome of the drive to get more NDAs and 510Ks is likely to mean carrying out more clinical trials, potentially with more sites/patients in more geographies. This all must take place in a commercial environment that demands increased cost-efficiency gains or more developmental output for less cost and increased effectiveness. Thus, not just more output but more effective output is required.

Expectations Of The Pharma Industry And 'Regulators'
Leaving the commercial pressures on the pharma industry to the side, let us look at society’s perspective — acknowledging there is no single concept of “society.” The significant increase in the quality and duration of human life that have resulted from the advances the pharma industry has made in therapeutic development — not the least of which has been in oncology and cardiac treatment — has been taken for granted, somewhat. There is a constant increase in expectation that ailments of all kinds can be ameliorated or cured for a reasonable cost — be it via health services provided through governments or via medical insurance. Moreover, there are key expectations that therapies are safe because they have been fully and appropriately tested in animal models and human trials. At the same time, society largely does not understand the commercial risk involved and the developmental dollars required to bring new treatments through the process that it demands, via governmental agencies (i.e. via the regulatory agencies).

Increase in patient expectation drives enhanced regulatory pressure. In response, the pharma industry is trying to embrace ways of carrying out clinical research more efficiently, and enhancing the relationship with regulatory agencies is a key component of this — to the benefit of society and the industry alike.

A global regulatory framework, typically operated via state/national governmental agencies, each with its own degree of autonomy, enforcement power, and scope, is a unifying thread. However, the extent to which each society’s regulatory expectations will be met tends to be a function of where one lives in the world.

The diversity within this framework has persisted even with the emergence over the years of genuine internationally accepted guidelines, such as those of ICH (International Conference on Harmonization). For example, although China’s GCP (good clinical practice) standards are essentially the same as those in the ICH E6 guideline, there are some differences, such as:
l ICH E6 GCP calls for investigators to report only unexpected and serious adverse events to IRB (Institutional Review Board)/ECs (ethics committees), but the GCP standards in China state that “any serious events that occur during the trials shall be reported to the Ethics Committee.”

• Chinese GCP standard states that the investigator must sign the informed consent form, while the ICH E6 GCP states that the subject and “the person who conducted the informed consent discussion” should sign.
• China’s SFDA (State Food and Drug Administration) insists that the clinical institution sets up a dedicated administrative office with full-time staff to provide oversight on clinical trial activities and outcomes. The office has to ensure local laws and regulations are implemented and establish a quality assurance system for the clinical trials according to GCP.

PricewaterhouseCoopers has reported that, by 2020, pharmaceutical consumption in the E7 country group (Brazil, China, India, Indonesia, Mexico, Russia, and Turkey) could account for 1/5 of global pharmaceutical sales. That is, of course, dependent upon the willingness (and ability) of the industry to further tackle those markets. While regulations in these new markets are often extensive and robust, the need for effective monitoring and enforcement processes remains if the industry and society do not want to erect barriers to the markets’ development.

Technology Helping To Square The Circle
Drug discovery has benefited from the use of sophisticated, software-based tools with the ability to process and analyze data and information in order to enable high-value, key decisions to be made more quickly and with a far higher degree of quantification. In clinical development — traditionally the most expensive phase of getting a new therapeutic agent to market — effective use of appropriate technologies is helping square the circle of meeting society’s expectations of the industry as expressed via its vehicle of choice: the regulatory agencies. This, in turn, ought to enable organizations to develop and bring to market new drugs or devices more quickly and effectively than has been the case historically and thus assist in the alleviation of the commercial pressures outlined above.

New ways of conducting the larger numbers of geographically dispersed and potentially more complex trials that will be needed to drive new therapeutic agent development are being utilized by much of the pharma industry. Increasingly, electronic data capture (EDC) — particularly EDC that is user-friendly and easy to deploy and manage on a global basis — is seen as essential to ensure timely and effective data analysis and decision making. Depending on the definition of EDC, phases of trials measured, and source of data, 50% to 70% of new studies are now being started using some form of EDC technology. The benefits can accrue throughout the phases of a clinical study, starting in Phase I, with some CPUs (clinical pharmacology units) running the gamut from fully automated units for local data capture and global transmission to analysis units that could be on the other side of the world. At the other extreme, the use of EDC potentiates the ability to carry out megatrials that will point not just to better efficacy data, but can also lead to better safety profiling as well.

With efficiently deployed EDC/electronic clinical data management (eCDM) as the core technology set, the industry can benefit from a technology integration strategy that will allow for more efficient digital data flows, particularly if it is based on standards such as those developed by the CDISC (Clinical Data Interchange Standards Consortium) and HL7 (Health Level 7) organizations. Combine efficient use of clinical imaging and the integration of EDC to best-of-breed system technologies such as interactive voice response systems (IVRS), laboratory systems (LIMS/HIMS), electronic patient reported outcomes (ePRO), and safety reporting, and the pharma industry has the potential for far greater clinical research and development productivity throughput. Outputs should include submission-ready data sets and better insight into safety profiling.

These systems and upgraded processes also provide regulators with the opportunity to look more deeply into key data (e.g. safety data) as well as make data easier to review and access during the approval process. Regulatory agencies are, in effect, society’s “Agents of Trust,” and the industry should and generally does embrace ways to assist them in this task.

Society expects a combination of therapeutic potency and high levels of safety from the products emerging from clinical development, and the industry does not want any more VIOXX situations. Working collaboratively with the regulators, who are sometimes ahead of the industry in seeing the benefits technology can bring, can potentially lead toward:

• Faster trial setups
• Enhanced trial conduct and analysis
• Trials capable of being conducted easily in multiple geographies and in local languages
• More timely submissions with the potential for faster approval times
• More effective late phase studies that provide continuous patient monitoring, which will provide a more real-world model of safety

Through more effective utilization of information technology, the opportunity exists for the relationships among society, the life sciences industry, and regulatory agencies to be redefined. All parties can benefit from the greater designation of technology-related standards at the global level to achieve their goals of bringing safe, new products to market in an efficient and timely way.

About The Authors
Tony Hewer is senior director of quality assurance for EMEA at Medidata. He is responsible for refining and maintaining robust, up-to-date quality and regulatory standards for Medidata’s products and services and ensuring the organization achieves compliance with these standards.

Steve Heath is the head of EMEA operations at Medidata. He has wide familiarity with selling and implementing EDC (electronic data capture), CDM (clinical data management), and ePRO (electronic patient reported outcomes) systems as well as LIMS, clinical project management, safety, and adverse drug reaction reporting systems.