Relationships between drug sponsors and investigative sites have become more effective during the past two years, according to a new CenterWatch survey, as the initiatives top sponsors have implemented in recent years to address site burdens—such as increased protocol complexity and insufficient study support—are beginning to have a positive impact.
Significantly, the 2015 CenterWatch Global Investigative Site Survey marks one of the few times in almost two decades that the industry has seen such strong improvement in sponsors narrowing the performance gaps across the attributes sites rated as most important in defining an effective relationship.
Top ranked companies were divided into two categories this year based on their total 2013 revenue from drug sales. The five highest-ranking large companies—with revenue greater than $11 billion—were Novo Nordisk, Takeda, GlaxoSmithKline, AstraZeneca and Janssen. The five small companies with the highest ratings—with revenue less than $11 billion—were Servier, Celgene, Biogen Idec, Otsuka and Forest Laboratories, which was acquired by Actavis last year.
Overall, the average sponsor received a combined excellent/good rating of 82%, a 2.5% increase from 2013.
Interestingly, the industry-wide movement toward patient-centered clinical re-search has forced sponsors to take a hard look at the quality of their relationships with sites; awareness has grown about the fact that patient experience in a clinical trial will not improve if sponsors neglect their relationships with sites. The survey results and interviews with senior executives suggest sponsors want to work more closely with sites and are focused on improving clinical trial practices for both sites and patients.
“The patient is at the center of what we do at Takeda, and we place great emphasis on understanding patient needs,” said Linda Atkinson, vice president of clinical operations at Takeda Pharmaceuticals International. “During development, our greatest connection to our patients is through our investigative sites, so it is important that we continue to work closely with our sites so we design and execute clinical programs with the patient at the center.”
The survey also suggested areas for improvement. Specifically, sponsors could improve their relationships with sites by providing protocols that require fewer amendments, supporting initiatives to help sites build stronger relationships with study volunteers and being more flexible in modifying protocols and budgets.
The 2015 CenterWatch Global Investigative Site Survey, conducted online from October 2014 through early January 2015, asked principal investigators, sub-investigators and study coordinators to rate the sponsors they worked with during the past two years on 38 project attributes. In addition, sites provided feedback on the importance of these attributes when conducting clinical trials.
Clinical research professionals representing 1,900 global sites completed the survey, with more than 75% of respondents from North America and Europe. A total of 24 sponsors with sufficient sample sizes were included in the analysis.
Sponsor rankings were based on a combination of two measures: an overall relationship quality rating based on the percentage of “excellent” scores from sites, and the frequency with which companies placed among the top-three rated sponsors across 38 relationship attributes measured.
For the first time in this biannual survey, sponsor rankings were split according to the size of revenue from drug sales because, as popularity and response to the survey has grown, the number of sponsors with sufficient sample size also has grown, which has allowed CenterWatch to provide a more granular analysis of performance.
Since it launched in 1997, the CenterWatch survey has become an important tool with which sponsors evaluate the quality of their relationships with sites and identify systems or processes for improvement. Novo Nordisk, for example, improved its data query practices using specific feedback from sites after the 2013 CenterWatch survey found its ratings in that area had slipped from 2011.
Gaps narrow in top attributes
Gaps narrowed between the importance of relationship attributes and the ability of sponsors to deliver them in each of the top nine areas sites rated as “very important” to their success. The most notable improvements were for specific project attributes that previous CenterWatch surveys identified as most critically in need of change: knowledgeable and well-trained monitors, for which the gap dropped from 26% in 2013 to 18% in 2015; organized and prepared study support, which fell from 22% to 16% between the two surveys; and easily accessible staff to resolve problems, which decreased from 17% to 11%.
Gaps also narrowed in another area sites rated as highly important: protocol/study design and planning. Increasingly complex and demanding protocols create additional work for site staff and complicate patient enrollment efforts. Yet the
importance-to-excellence gap between 2013 and 2015 narrowed from 19% to 15% for the average sponsor in providing good overall protocol design, and from 17% to 14% for having protocols aligned with clinical practice realities.
Importantly, while the ability to remain among the top-ranking sponsors from one survey to the next historically has been elusive, the 2015 survey found greater consistency in the companies ranked among the highest performing sponsors. Takeda and Novo Nordisk also were rated in the top five in the 2013 survey. Furthermore, Novo Nordisk was the top-ranked company in the 2011 survey. Boehringer Ingelheim and Biogen Idec, top performers in the 2013 survey, also were rated highly in 2015. AstraZeneca and Amgen, top performers in 2011, also received high ratings for direct working relationship quality in 2015.
These findings suggest top ranking sponsors are getting better at creating continuity in their R&D practices and, as the importance-to-excellence gaps narrow, initiatives they have implemented in recent years are beginning to positively affect the quality of their site relationships.
Boehringer Ingelheim, which was among the first sponsors to form internal protocol review processes, ranked among the top three companies in both 2013 and 2015 for having protocols in which scientific rationale is aligned with clinical practice realities. Its review processes, which began five years ago, typically include asking investigators, monitors, data managers and other experts for feedback about protocol feasibility, including whether inclusion/exclusion criteria makes sense. In addition, a Protocol Challenge Committee (PCC) evaluates protocols six to eight months before study initiation and requires justification for the number of procedures required, how often they are performed and the effort required for sites to administer them.
The PCC process, which has helped reduce study complexity and streamline protocols, combined with improvements in the company’s protocol feasibility process and better oversight of recruitment activities, have allowed sites to more quickly recruit patients. During the past five years, Boehringer Ingelheim has increased its on-time recruiting from 30% to 55% of its trials.
“Gathering operational input from physicians who will be recruiting patients at a time when this information can help change protocols for the better makes sense,” said Mark Hopley, M.D., head of central clinical operations, and clinical operations for Europe, at Boehringer Ingelheim, who helped establish the PCC. “Sites have seen their feedback change and improve protocols. This responsiveness by Boehringer Ingelheim is noted and appreciated.”
Takeda ranked among the top three sponsors in both 2015 and 2013 for having knowledgeable, well-trained monitors, which is the one project attribute investigators consistently have ranked as the most critical relationship success factor. Investigators want to work with monitors who know the protocol, understand how sites work and can help solve problems. Even when monitors are hired and managed by CROs, sites believe sponsors are responsible for setting training and professional standards for all CRAs working on their studies.
While Takeda has two strategic partnerships with CROs that manage its monitors, as the sponsor it provides ongoing monitoring oversight to ensure quality and performance expectations. Takeda also makes sure it attends internal CRO training sessions for support and direct interactions with its monitors.
Partnering with only two CROs has enabled Takeda’s CRO team members to work on Takeda studies for many years, which brings consistency to its overall study delivery. In addition, Takeda connects with its CRO partners early in the study design process, and key CRO team members contribute to design and planning discussions; this gives the CRO background behind scientific and operational decisions, enabling them to provide monitoring staff the context behind decisions and better understanding of unique challenges of specific Takeda protocols.
“We recognize and appreciate the hard work of our monitors, and this helps them to feel valued members of our team, which we believe helps in retaining quality monitors,” said Atkinson.
Takeda also showed consistently strong performance, ranking among the top three sponsors in both 2015 and 2013, for another critical area in which the importance-to-excellence gap has narrowed: Having staff easily accessible for escalation of issues and providing timely resolution. If a monitor employed by a CRO can’t resolve a problem, or doesn’t know where to turn for an answer, sites report difficulties and delays in getting the issue resolved.
“We work to reduce the burden on our sites and look for opportunities where we can maximize support,” said Atkinson. “Our sites and CRO partners are provided with clear escalation pathways to ensure we can resolve issues expeditiously. Communication is key, and we leverage many different tools including web portals and other technology solutions. We continuously are working with our CRO partners to assess innovative technologies that will reduce the burden for site staff. For example, we often take advantage of technology supporting virtual meetings to provide training to sites without travel burden.”
Higher excellent ratings
Average sponsor performance in the 2015 survey generally improved or stayed the same, compared to 2013, on the 38 individual project attributes measured. The average excellent rating across all attributes increased from 44% in 2013 to 47% in 2015.
Work style issues were among the top areas of improvement, particularly empowering staff to make level-appropriate decisions, for which excellent ratings increased 6%, and having a supportive culture and creating a collaborative team environment, two attributes that both saw excellent ratings increase 4%.
Biogen Idec, which had the highest percentage of excellent ratings from sites for giving staff power to make level-appropriate decisions (60%), has changed its outsourcing model to empower staff in its affiliates to deal directly with sites in their individual countries. Biogen Idec, which outsources 100% of its studies to CROs, early last year moved from a transactional model that worked with about five providers to a sole partnership with Quintiles, which allowed it to better align goals, roles and responsibilities throughout the partnership and specifically throughout global clinical operations.
“It’s still early days. But what it attempts to do is give people space to work and clear roles and responsibilities,” said Murray Abramson, vice president of global clinical operations at Biogen Idec. “People will respond because you have put high-quality individuals in meaningful positions and you allow them to act effectively within a partnership. In building these bridges with our sole partner, it really allows them to have the autonomy they need to make decisions and the support that they need. We are trying to build the relationship with our CRO and truly treat each other as co-workers.”
Biogen Idec also received the highest percentage of excellent ratings (59%) for creating a collaborative work environment, which Abramson said is an important part of his company’s culture. Two other sponsors—Celgene and Novo Nordisk—received the same score for this attribute.
“We are here to support the patient. I know it sounds very trite. Everybody says that. But when the rubber hits the road, when issues have to be decided upon, the patient is always number one for us,” said Abramson. “I’m speaking not only as a company, but also global clinical operations. For us, it’s not collaborating for the mere sake of collaborating. It’s collaborating because we see the bigger picture—whether it be Alzheimer’s disease, multiple sclerosis or hemophilia,” Abramson said. “The team is totally dedicated. There is tremendous power in all of our employees and in unleashing them and aligning them on what is really important.”
Excellent ratings also increased in the study monitoring support category, in which a larger percentage of sites in 2015 gave sponsors high marks for providing ongoing help in running the study (53%) and low monitor turnover (43%).
Novo Nordisk, which has maintained strong overall performance across the past three CenterWatch site surveys, ranked among the top three companies this year for ongoing help in running the study (61%), low monitor turnover (54%), offering organized and prepared study support (65%), being responsive to inquiries (60%) and having easily accessible staff (63%). Kate Owen, vice president of clinical trial management at Novo Nordisk, credits a sourcing model, which relies almost entirely on in-house Contract Research Associates (CRAs), along with long-established practices that routinely ask sites for feedback about ways to improve, as key to the company’s consistently strong and effective site relationships.
“Continuity goes to two things: Listening to what your sites need of you, as a sponsor, and being able to do that more effectively through your own staff,” said Owen.
While the majority of sponsors outsource clinical trial monitoring to CROs, at Novo Nordisk 80% of U.S. sites and 100% of ex-U.S. sites are supported by in-house CRAs. Insource staff, who are put through Novo Nordisk’s entire training program and held to company expectations, are employed in areas where the workload doesn’t justify a full-time employee. Each site is assigned a field CRA for monitoring visits and a specific in-house CRA who is available any time to address protocol questions and other needs.
“Sites want greater touch points with the sponsor,” said Owen. “It’s great having investigator meetings and protocol development meetings with sites and asking for their feedback. But having somebody they know and have a professional relationship with—and the ability to pick up the phone at any time and always get that person—is incredibly important. Time and time again, our sites tell us they feel more in touch and more appreciated and valued because they talk to employees of Novo Nordisk. And that isn’t what most pharmaceutical companies are doing.”
The turnover rate for Novo Nordisk monitors in the U.S. was 5% last year and the average CRA’s tenure spans 15 years, unusual for a job with high burnout rates across the industry. About five years ago, in response to requests from CRAs for a better quality of life and less travel, the company moved to a regionalized monitoring model, in which monitors must live with 50 miles of the patient hub. The policy gives monitors a better work-life balance and, from a business perspective, results in more monitoring days a month and lower travel costs. Importantly, it also means sites get the consistency of the same monitor for all study visits.
“What it really brings is such a high intensity and capability to support your sites,” said Owen.
In the 2015 survey, sponsors also improved their performance in financial attributes. While sites typically give this category the lowest ratings, excellent ratings for fair overall grant payments improved by 7% and realistic grant payment schedules increased 6% since 2013. And while only 41% of sites gave sponsors an excellent rating for promptness in grant payments, performance on this attribute improved 5% from 2013.
Yet, sponsors being willing to modify protocols or budgets received an excellent rating from only 38% of sites. Sites also gave low marks for providing protocols that require minimum amendments (37%).
While the average sponsor has improved efforts to help sites build stronger relationships with study volunteers, the attribute remains one of the lowest rated in the survey (41%). However, the survey did show a 6% improvement from 2013, as well as a 3% improvement in providing assistance with patient recruitment efforts. Both are important areas for successful patient-centered research.
“We recognize that to be successful in the future we will need to increase the involvement of patients in the clinical development process and be more patient-centric in our approach during the development of the protocol, as well as during and after the clinical trial,” said Ann Van Dessel, head of global clinical operations at Janssen Research & Development.
The higher excellent marks across the board reflect the fact many sponsors are spending more time and resources on new initiatives and processes that can streamline clinical trials, making it easier for sites to conduct successful studies and strengthening relationships with both sites and patients.
“We recognize the invaluable benefits that sites bring to this partnership, not just access to the patients we enroll in our trials but expertise that makes our protocols better,” said Barbara Grassi, head of global in-country clinical operations at Glaxo-SmithKline. “Sites are front and center in the clinical development process.”
Takeda and Novo Nordisk are among sponsors that hold routine feedback sessions with its sites to identify challenges and look for opportunities to provide further site support. Takeda also works closely with high-recruiting, high-quality sites and connects them with sites having recruitment challenges to enable sharing of best practices. GlaxoSmithKline creates partnerships with its investigators and draws on site staff expertise when developing protocols.
“More and more we recognize the value of getting the practical view of investigators earlier in the process of developing protocols. The investigators and coordinators can validate our thinking about entry criteria and feasibility, which are critical factors to the successful conduct of a study,” said Elyse Seltzer, M.D., vice president of global clinical sciences and operations at GlaxoSmithKline.
Biogen Idec formed a customer excellence organization to help set strategic goals, ensure teams listen to site and patient experience and incorporate those perspectives into the way they design a study or program. It recently began a thorough inventory of all global clinical operations activities to understand what touches sites and how sites view those activities. The company also has begun an initiative to consider how its partnership with Quintiles adversely or positively affects sites.
“Both within our organizational structure and also in our discussions of projects, we are always looking to understand how it affects the sites, how it affects the subject/patient. We are always looking to improve,” said Abramson. “There are a lot of opportunities to optimize the relationship and we use the resources we have at Biogen within developmental sciences and within global medicine to do just that.”
Small or large, performance similar
The 2015 survey, which for the first time differentiated sponsors based on their level of revenue from drug sales, found no significant difference in the percentage of excellent ratings as a function of company size. While smaller sponsors commonly are thought to be more intimate and give sites more attention, the average rating for large and mid-sized sponsors was 48%, compared to 46% for small sponsors.
Novo Nordisk’s Owen said sites often have more contact with smaller sponsors and that contact is at more senior levels of the organization because of less bureaucracy. But, she said, a large pharmaceutical company could offer stability and more robustly defined processes.
“The sites want to be able to move forward in a consistent pattern, a consistent way of working because it makes their lives easier. And that is what big pharma brings,” she said. “Novo Nordisk has really tried to have big pharma policies and procedures that enable consistency and standardization, but we very much need to be an organization that understands and is in contact with our key stakeholder, which is all levels of site staff.”
Areas for improvement
While sponsors have closed the importance-to-excellence gaps in the short term, the average sponsor has not been able to reach the performance levels they achieved four years ago. The percentage of excellent scores in each of the top nine attributes rated ‘very important’ fell between 2011 and 2015 and are more in line with results from the 2009 U.S. sponsor-site survey.
Factors that could explain this decline include the increased level of outsourcing to CROs, which results in less direct contact between sponsors and sites. Only half of the sites surveyed gave sponsors high marks for working effectively with CROs, and investigators expressed frustration with not having enough access to sponsor staff when issues escalate and must be resolved. Recent research also shows protocols have become increasingly complex, creating further demands on site staff and making it more difficult to enroll patients into clinical trials.
In addition, sites feel the burden of maintaining quality but don’t always feel the challenges are fully understood by either the sponsor or CRO. The lower scores could reflect the fact investigators have become more vocal about wanting more input into how trials can be run more efficiently and how to improve operational issues, from patient recruitment strategies to the use of technology at the site level.
The 2015 survey suggests, in particular, that sponsors may need to find new ways to reach out to their more experienced investigators who have witnessed changes in the clinical trials landscape. Investigators with more than 10 years of experience gave sponsors a lower overall excellent/good rating (81%) than did those with five to 10 years’ experience (83%).
While the gaps have narrowed in areas important for site success, the survey suggests investigators want sponsors to continue improvement efforts. The widest performance gaps between importance and excellence remained in areas best met by staff on the front lines—well-trained, knowledgeable CRAs, organized and prepared study support and easily accessible staff—along with having good protocol design aligned with clinical practice realities.
And two new survey attributes received some of the lowest ratings from sites, although they were not rated among the top 10 in terms of importance: Actively soliciting feedback on protocol design (39%) and reviewing a clear plan for handling monitor turnover (41%).
Survey results suggest the initiatives sponsors have undertaken in recent years are beginning to pay off, yet they still must stay focused on strengthening their relationships with sites and look for opportunities to address site concerns. Top ranked sponsors already have shown that looking for ways to decrease study burden and protocol complexity can help build stronger sponsor-site relationships, which can lead to more predictable, higher-quality site performance.
“We plan to continue to engage early with our sites and ensure ongoing dialogue with them, as appropriate,” said Takeda’s Atkinson. “We want to continue building upon the foundation and find ways to ease the ever-increasing complexity of clinical trial burden for our sites.”
Karyn Korieth has been covering the clinical trials industry for CenterWatch since 2003. Her 30-year journalism career includes work in local news, the healtcare industry and national magazines. Karyn holds a Master’s of Science degree from the Columbia University Graduate School of Journalism. Email email@example.com.
Annick Anderson has been conducting market research since 1998 in both the health care and consumer packaged goods industries. Annick holds a Master’s of Business Administration from the Boston University Graduate School of Management. Email firstname.lastname@example.org.
Sponsors interested in purchasing comprehensive reports on their individual results of the 2015 CenterWatch Global Site Survey can contact Joan Chambers at (617) 948-5110 or email@example.com. Custom reports provide company-specific results compared with benchmarks and with past company-specific findings.
This article was reprinted from Volume 22, Issue 03, of The CenterWatch Monthly, an industry leading publication providing hard-hitting, authoritative business and financial coverage of the clinical research space. Subscribe >>