January 1, 2014 (Vol. 34, No. 1)

Jeanene Swanson

From our January 1 issue: In a clinical trial, a CRO may provide a brief solo (a niche service) or the whole symphony (preclinical to post-approval services).

The drug development process is vast, involving a nearly symphonic coordination of many disparate players—trial sponsors, contract research organizations (CROs), and institutions such as academic medical centers and hospitals.

Each of these players adds a distinct part to an integrated whole.

Over the past two decades, sponsors within the pharmaceutical, biotechnology, and medical device industries have come to rely on CROs to perform the actual work of a clinical trial. A CRO can provide some or all of the following services: biopharmaceutical development, biologic assay development, commercialization, preclinical research, clinical research, clinical trials management, and pharmacovigilance.

Evaluating when and how to utilize a CRO means examining its capabilities—larger CROs tend to offer a comprehensive range of preclinical, clinical, and post-approval services, whereas small CROs tend to focus on specialty areas and niche offerings.

Large sponsors already have preferred vendor networks and optimized standards for evaluating, contracting, and managing CROs. Small sponsors often don’t have internal teams to support a CRO relationship, and some don’t even have a team to select the CRO or vendor, says Katie McCarthy, a principal consultant at Halloran Consulting Group.

McCarthy says that the three most important factors for a small sponsor in choosing a CRO are credibility, capability, and budget. Small sponsors should get to know the vendor and go through the formal selection process. “Meet the actual team that will be working on your program as part of the selection process,” she says. “Be honest about [your] needs—where the gaps are, how involved the board is, how frequently updates will be required.”

Whether to hire a big or small CRO is another question for small sponsors. When it comes to working with big CROs, “small sponsors are at a disadvantage,” contends McCarthy. “They don’t offer enough business to keep the bigger companies interested in them from a volume perspective.”

Small sponsors might consider the benefits of partnering with small CROs. “Small CROs can often be more flexible and understanding,” offers McCarthy, “and they often understand the ‘high touch’ needs of small sponsors.” Plus, prices can often be more reasonable.

Some of the drawbacks to using small CROs, McCarthy notes, are a lack of staffing resources, limited expertise, and older clinical trials management systems. “Larger CROs often have the expertise, systems, and infrastructure that smaller CROs may not, but it can be more difficult for a smaller sponsor to retain key resources for their programs.”

Building Relationships with CROs

When it comes to developing solid relationships with CROs, the biggest challenge is establishing trust, says Mack Rubley, Ph.D., director of business development for Boston Biomedical Associates. “[It] is not unlike a parent sending their child to school. The parents need help, but are concerned about who will be helping the child.”

Once trust is established, the largest concern is flow of information. “The most effective partnerships occur when information is shared in real time, and a CRO does not surprise the client,” Dr. Rubley advises.

“From our perspective, many of the challenges arise from miscommunication and/or management of expectations,” remarks Paula Brown Stafford, president of clinical development at Quintiles. According to Stafford, keeping lines of communication open, managing timelines, maintaining high-quality patient data, and establishing shared metrics are must-haves when establishing truly integrated sponsor-CRO relationships.

A prime initiative for Quintiles has been improving relations with investigator sites. “The research happens at the investigational site and anything that can be done to support site staff so that they can focus on the patients must be a priority,” she says. This includes taking the administrative burden off sites, including start-up activities and regulatory paperwork.

The biggest challenges to establishing integrated relationships, according to Dr. Rubley, are differences in business practices between partners, financial forecasting, and communication. Stafford adds that it’s important to have an understanding of the services that will be delivered as well as definite plans and clearly defined roles and responsibilities. “Some of the biggest challenges to effective integration are differing technologies and operating procedures,” she remarks. “These can be overcome, but it does require experience and coordination.”

After a sense of trust, the next largest concern about working with a contract research organization is flow of information, which must continually be shared between the CRO and the client company.

Coping with Consolidation

In the past several years, big pharma and biotech have not only seen a wave of consolidations, but internal research budgets have been shrinking among all drug development organizations, according to a recent report released by the Tufts Center for the Study of Drug Development. The report, which reflects the views of drug industry leaders, argues that many sponsors see the exploration of new paradigms as a way to deal with impending patent expirations and investor demands for faster development of new drugs.

There has also been consolidation among CROs in the past few years, says Peter Sullivan, vice president and principal with the Sullivan Group, which provides insurance and risk management services to the industry. “There has been a big movement in the CRO industry [whereby] larger companies have looked to increase their depth of professional services [by acquiring] other small companies who can fit the niche that they want to fill.”

Not only are larger companies buying smaller ones, but smaller ones are also scrambling to merge, according to Michael Martorelli, director of investment banking firm Fairmount Partners. “If you’re going to fight consolidation, you’re fighting a losing battle,” he says of the CRO industry.

In a recent report on the industry, Martorelli highlighted that in this “new era of strategic partnerships,” there are signs that many sponsors are consolidating the number of CROs they’re using. In fact, CenterWatch recently noted that 87% of the 30 largest drug companies have at least one multiservice agreement with a CRO, whereas in 2004, only 47% of those same companies did. Thus, says the report, “having the ability to provide a range of services across the pre-clinical, clinical and post-approval segments of outsourcing might become more of a competitive advantage than it’s been in the past.”

However, small and midsized CROs should stay focused on what they do best—offering a limited range of specialty services for specific therapeutic areas—instead of trying to partner with bigger companies. While large CROs will continue to consolidate to provide a greater breadth of services, sponsors might end up going with a small, niche company regardless. “Big pharma and med tech need to find the most economical way to get a trial done, and it may not be with the big guy, it may be with a smaller one who is more nimble,” Sullivan suggests.

Employing Crowdsourcing

Recently, a trend to make clinical trials more patient-centric has been emerging—using new technologies such as cloud computing and remote sensing devices to improve the way sponsors recruit patients, design trial protocols, and manage data.

Crowdsourcing is “enabling lay members of the public to engage in activities normally restricted to trained scientists,” says Paul Wicks, Ph.D., director of R&D at PatientsLikeMe, which works to raise awareness and improve patient matching in clinical trials.

“What we’re interested in is enabling patients to become not just subjects but active participants in trials,” Dr. Wicks explains. This involves creating tools that allow patients to give feedback to protocols—whether the types of data collected makes sense for someone living with the disease, or how convenient participating would be, for example. “If we can help trial designers quickly iterate on their protocol, we’ll maximize patient engagement and create a whole new type of dynamic clinical trial—the community trial,” Dr. Wicks asserts.

Transparency Life Sciences (TLS) is one drug company leading the charge. Its clinical trial protocol to assess lisinopril as an adjunctive therapy for multiple sclerosis, which was cleared by the FDA last December, was the first approved protocol developed with the aid of crowdsourcing. It is also among the first to make extensive use of telemonitoring and other remote patient data collection. TLS’s Protocol Builder™ tool can be used to obtain input from a patients, physicians, and researchers to help design clinical trials more efficiently and with more relevance to clinicians and patients’ needs.

“Crowdsourcing is part of our larger effort [as a drug development company] to completely change the way drugs are developed,” says Tomasz Sablinski, M.D., Ph.D., founder and CEO of TLS. It’s “giving patients a powerful voice” in the trial, Dr. Sablinski says, while it enhances openness and transparency, and digitizes the way trials are monitored. TLS has a number of new projects in the works, including the design of crowdsourced protocols for studies of pioglitazone in Parkinson’s disease and metformin in patients with recurrent prostate cancer.

While challenges remain for crowdsourcing, including low numbers of relevant patient participants and biased patient demographics, Dr. Wicks expects these tools to become must-have’s in the near future: “Today trial recruitment is increasingly done online, but is mainly limited to generating awareness. In the future, we expect more companies will use online, crowdsourced tools to design their trials and tap into the patient community.” Dr. Wicks predicts that more capable online platforms will soon be in wide use, with a growing trend to “communicate the summarized results of trials back to the patients who participated, and to others.”