A Global Systems Approach To Clinical Research

By Fred Olds, contributing editor

“It would be an enormous benefit to pharma and humanity if we had a more efficient and systematic way to bring safe and effective drugs to market,” says Greg Koski Ph.D., M.D., CEO, president and cofounder of the Alliance for Clinical Research Excellence and Safety (ACRES). He asserts that the current approach has evolved into a multisiloed proprietary arrangement.

Everyone knows it’s an inefficient mess, and many believe it’s unsustainable.” He proposes a better approach — a system.

Koski and collaborators envision ACRES as the nexus of a global research system. They propose establishing a worldwide network of accredited clinical study sites and research professionals supported by a shared information technology platform. These would operate under common standards and use common procedures agreed to by international stakeholders in clinical research.

ACRES was conceived out of frustration with attempts to bring harmony to the current state of clinical research. There were, and are, many good organizations working to fix or improve specific areas of research, but, Koski says, “That’s like having a 1954 Chevy that you work on to improve. You can replace parts and repair all you want, but in the end you still have a 1954 Chevy.” What is needed, he says, is a revolution of thought and behavior. He says, “ACRES isn’t a piecemeal fix; it replaces the current inefficient processes with a true system. Think of it as ‘next generation.’”

He points to the International Air Transport Association (IATA) which led efforts in the development of universal standards for aviation. ACRES patterns itself on the success of the IATA. Like IATA, it is both a forum for the exchange and implementation of ideas as well as a vehicle for establishing standards. It is an alliance of stakeholders in clinical research including sponsors, investigators, vendors, and regulators. It was founded as a not-for-profit organization to remove any doubt about its motives, actions, and recommendations.

The Rationale of Quality, Time, and Money
The alliance is based on the concept that a universal system of standards, accreditation, and technology will reduce costs and speed time to market for therapeutics, while enhancing quality and safety. Koski contends the current processes are inefficient. “Of the $70 billion spent on clinical trials, about 30 percent is wasted,” he says, “That’s more than $20 billion left on the table.” For example, even with the best selection techniques, fewer than one-third of trial sites will enroll more than one or two patients, and 10 percent will enroll none at all. Costing $25,000 or more, development of a site can be a large investment with nominal returns.

Having established/accredited sites means improvements in quality, time, and money related to the trials. Koski estimates that access to high performing sites can shave two to three years off time to market. A comprehensive global database will speed screening for appropriate sites based on, for instance, desired patient populations or site capabilities. Access to existing equipped sites that are staffed by trained professionals will cut start-up time. The ACRES global technology network will provide real-time monitoring so potential issues can be identified and resolved early. Application preparation will be easier because data will have been collected in real time and in a uniform manner. Regulators relying on ACRES accreditation may find reviewing applications easier, because all sites used standard operating procedures.

Koski believes it is imperative to establish consistent global standards. “Seventy percent of clinical trials are now conducted in North America and Europe. In the next decade, that is predicted to change, as trials shift to China, India and other parts of the world,” he says. With conflicting regulations, standards, and local customs, there are difficulties in reconciling policies and procedures in one part of the world with those used in another.

Under the ACRES umbrella, sites will be interoperable; they will be using the same systems. That means communications and oversight of multicenter studies will be consistent, regardless of location. Researchers won’t have to deal with computer interface difficulties nor differences in procedures because of local variations in equipment or practices.

A Global Technology Network
Connectivity is at the core of the system. “Develop the system, and the system will drive standardization,” says Koski, “Standardization will improve efficiency, quality, and safety. If there is no system, then sponsors will have to adapt studies to each country.”

Systems engineers are creating a global technology network using off-the-shelf equipment. Doing so is economical and creates a network that is capable of aggregating, analyzing, and sharing information globally in real time. Koski says an authorized researcher or regulator anywhere in the world will be able to access the system to find the required information. “It’s much like our ability to find flight schedules on the other side of the globe because of IATA’s database,” he says.

Dynamic Accreditation and Excellence
“Industry has failed to recognize the value of promoting excellence at research sites,” says Koski. Accreditation will reward site excellence. Sponsors looking to place studies will be able to screen sites, looking for those that perform efficiently and quickly. Site operators wishing to draw studies to their centers will manage their operations to meet the standards of the highestperforming centers. “Not everyone wins. High quality wins — inefficient, poorquality sites will not be sustainable,” says Koski.

Sites will be accredited by agencies empowered by stakeholders in the ACRES system. Once approved, a site will continue to be accredited dynamically. Work at study locations will be captured in real time. Systems will continually monitor the environment, equipment, and media for review and analysis. Input by staff will provide current progress on research. All of this will give assurances to the sponsor, public, and regulators that research was conducted properly and allow accreditors to assess the work conducted by the research site. Koski asks, “Does it make sense to go eight years developing a new molecular entity only to have it fail to win approval due to an error in process?”

Site accreditation is one of the core initiatives ACRES is tackling. At present 120 international experts from all sectors of clinical research are engaged in ACRES’ initiatives, including development of procedures and standards for clinical trials. It is reviewing international regulations, science, and best practices to seek consensus on, and then establishment of standards for, adoption by ACRES. The first version of site accreditation standards should be available for testing by early 2015. Round one of actual accreditation should take place by the third quarter 2015.

Hurdles To Expanding Healthcare In The Third World
“A big challenge for healthcare is that the majority of people in the world don’t have access to medicine or medical care,” says Koski. Much of the research in the third world is “one-and-done.” It’s helicopter research. A company comes in and completes a trial then departs without leaving any lasting benefit to the country or its people.

ACRES established the Global Challenge initiative to develop world-class permanent clinical trial sites in the developing world. It believes a location staffed with medical and research professionals will not only draw research but also serve as a hub for medical services to the people of the country. The first accredited pilot project for the challenge is planned for Bangladesh.

Changing the world in a big way has big challenges. Funding is an immediate one. ACRES is embarking on a $50 million director’s campaign to build infrastructure and core systems components. These components are key to operations because they form the backbone of the global technology network.

"Of the $70 billion spent on clinical trials, about 30 percent is wasted." Greg Koski Ph.D., M.D., CEO , president and cofounder of ACRES

Once online, ACRES can be financially self sufficient in three and a half years. It has identified potential funding streams from site-related connection fees, user fees, and royalty streams. In time, there should be as many as 180,000 sites in the network. Revenues of about $250 from each of 65,000 of those sites would be sufficient to support the global system.

Inertia may be the greatest obstacle for ACRES. Changing the culture of secretive siloed research is not easy. Koski agrees it will be a challenge to convince sponsors to provide open, transparent data on their trials. Countries may resist adopting universal standards. Habits and suspicions are difficult to change. The fear of losing intellectual property or local customs is a difficult psychological and practical obstacle.

While accepting the challenges, he says there are currently 46 strategic allied organizations that believe in the value of ACRES and are actively involved in the effort. ACRES is relying on them as advocates. As major sponsors like Pfizer or AstraZeneca make clear they intend to use ACRES standards for their trials, countries interested in working with them will strive to raise their standards to attract the trials. If the allied companies do cut time to market and enjoy easier coordination of research, others will follow.

“It is safer to fly from an airport in one country to an airport in another country than it is to drive to your local airport,” says Koski, “That’s because of the system that IATA has helped build.” He believes ACRES can be the correlative agent to bring higher quality, efficiency, safety, and standards to clinical research.