april 2015 a special centerwatch feature article reprint ... · the ability to resolve problems...

The CenterWatch Monthly (ISSN 1556-3367). Volume 22, Issue 04. © 2015 CenterWatch centerwatch.com

Strategic outsourcing prioritizing, improving site relationshipsBy Karyn Korieth and Annick Anderson

Contract research organizations (CROs) have become more effective in managing working relationships with investigative

sites during the past two years, according to a new CenterWatch survey, yet the average CRO continues to fall below performance ex-pectations in many of the areas investigators consider most critical for study success.

In the 2015 CenterWatch Global Investi-gative Site Survey, CROs overall received a combined excellent/good rating of 80%, a 2% increase from 2013, and the average CRO im-proved its performance in several key areas, including working effectively with sponsors and conducting clear study initiation visits and training.

Yet more than half of sites surveyed gave CROs low marks for ensuring study monitors are well-trained and understand the protocol, the ability to resolve problems quickly, ade-quate patient recruitment support and timely grant payments, all areas that CROs increas-ingly are managing for sponsors.

Five CROs came out on top: PSI CRO, INC Research, Chiltern, PPD and Covance. INC Research, PPD and Covance also ranked among the top five CROs in the 2013 survey; PSI and Chiltern were not included in the

rankings two years ago due to insufficient sample sizes. Quintiles, a strong performer in the 2013 survey, also was highly rated in 2015 for the quality of its site relationships, plac-ing sixth on the list. Filling out the list from numbers seven to 11 were Medpace, Icon, PRA Health Sciences, Parexel and inVentiv.

Importantly, CenterWatch analysis suggests as sponsors increasingly adopt integrated and strategic outsourcing partnerships that give CROs greater responsibility for selecting and managing sites, the average CRO has made great strides in improving its working relation-ships with sites. In fact, the proportion of sites giving the average CRO an excellent rating has nearly doubled in the past decade, increasing

from about 25% in 2003 to 45% this year.“We want to understand a site’s needs and

help them be successful,” said INC Research CEO Jamie Macdonald. “The CROs have real-ized that it’s about more than just coming on site, assessing the protocol and going through the mechanics. It’s really about understanding the sites’ needs, the challenges they face and being an advisor and provider of solutions. And I think sponsors are empowering CROs to take the additional time needed to support the site and not just do the mechanical side of clinical trial monitoring. Managing site rela-tionships does take time and effort.”

CROs increasingly recognize that build-ing strong relationships with experienced,

PSI, INC Research, Chiltern best with sitesApril 2015 A Special CenterWatch Feature Article Reprint Volume 22, Issue 04

Top performing CROs 2015 Average investigative site rating of CRO ability to deliver on a given attribute

CRO Sample size ‘Excellent’ ‘Fair’/’Poor’PSI 75 54.9% 5.3%

INC Research 259 49.3% 4.9%

Chiltern 87 48.6% 4.0%PPD 729 47.4% 5.8%

Covance 614 45.5% 4.3%

Quintiles 1,006 45.1% 5.5%

Medpace 75 42.8% 3.3%

Icon 532 41.7% 5.7%

PRA Health Sciences/RPS 182 41.7% 5.5%

Parexel 537 41.2% 7.3%

inVentiv 86 34.2% 10.0%

Source: CenterWatch 2015; N= 1, 900 investigative sites rating CROs on 37 relationship attributes

“A close site relationship built around trust, transparency and quality performance can go great lengths to eliminating the friction areas that have existed historically.”—Susan Romberg, vice president of global clinical development at Chiltern

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high-performing sites is not just critical to the success of the clinical development pro-cesses they manage for sponsors, particularly as studies become more complex and include more procedures. Relationships also have be-come an important competitive advantage as investigator turnover rates continue to rise.

“We know for a fact that site performance is a function of the relationship that we build or don’t build with a site. The clinical trial land-scape has become very competitive, and in the future our ability to establish solid, trusting relationships with sites will separate successful CROs from the rest of the crowd,” said Olga Alfonsova, global head of business develop-ment at PSI.

Survey methodology

CenterWatch’s 2015 Global Investigative Site Survey, conducted online from Octo-ber 2014 through early January 2015, asked Principal Investigators, Sub-Investigators and Study Coordinators to rate the CROs with which they worked during the past two years on 37 project attributes. In addition, sites provided feedback on the importance of these attributes in conducting successful clinical trials.

More than 72% of the 1,900 clinical research professionals who completed the survey were from North America and Europe. A total of 11 CROs with sufficient sample size were evalu-ated in the 2015 survey, compared to eight CROs in the 2013 survey.

CRO rankings were based on a combina-tion of two measures: an overall relationship quality rating based on the percentage of ex-cellent scores from sites, and the frequency with which companies placed among the top-three rated sponsors across the 37 attributes measured.

The CenterWatch survey not only high-lights the importance of sites to the clinical development process, but the investigator sat-isfaction ratings also are vital to CROs, since their success in managing a clinical study depends on the quality of their relationships

with sites. Many companies use this biannual survey as a road map for evaluating the effec-tiveness of their site relationships and identi-fying systems or processes for improvement.

Overall excellent ratings increase

CRO performance in this year’s survey generally improved or stayed the same, com-pared to 2013, on each of the 37 individual attributes measured. The average excellent rating across all attributes increased three percentage points during the past two years, which is statistically significant. CROs nar-rowed performance gaps five to eight percent-age points across the five attributes sites rated as most important to study conduct success: knowledgeable and well-trained monitors, organized and prepared study support, timely drug availability, easily accessible staff for is-sue resolution and professional medical staff.

The results underscore how CROs, under mounting pressure to achieve higher levels of performance and efficiency, have focused ef-forts in recent years on developing more effec-tive relationships with sites to improve clinical trial operations.

“For us, it’s about developing what we call ‘blue ribbon’ partnerships. It’s about under-standing at a fundamental level what each partner needs to bring about that relation-ship,” said Jill Johnston, vice president of global site activation, informatics & optimiza-tion at Covance. “We need sites that provide high-quality data, patients who are going to be eligible for the study and migrate into the study in a short amount of time for us to reach our goals. But on the flip side, we also have to be really good partners for sites to make sure they understand that we also are in it for them. We need to make sure we are contributing the right amount of information and making it easy for them to do the studies.”

Leading CROs have begun new programs and initiatives in recent years to improve communication with investigators, address site needs and better leverage site relation-ships. These CROs have developed preferred

2 The CenterWatch Monthly | April 2015 centerwatch.com

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partnership programs, invested time and re-sources into training programs, given inves-tigators insight into industry pipelines so they are ready for upcoming studies, offered great-er support for patient recruitment efforts and asked sites for feedback on how to improve the quality of their relationships.

“An effective relationship is built on com-munication; specifically, two-way commu-nication. When they contact us, they expect a reply. When we contact them, we expect a reply. With both phone calls and e-mails, nearly every CRO has become effective at communication and that does help make for a good relationship,” said David Scott, president and CEO at Palm Beach Research, a Florida-based dedicated research center.

CROs also have participated in initiatives sponsored by TransCelerate BioPharma, which aims to streamline processes and re-duce redundancies for sites, as well as projects begun by the Society for Clinical Research Sites (SCRS) to advance the role of sites in clinical research.

“We have offered sponsorship and scholar-ships to the SCRS program to allow sites access to the SCRS offerings, which include work on training best practices, advocacy for the role of sites globally, communication and a network through which sites can share ideas, thoughts, concerns and needs. We then internally take that feedback and use it to drive initiatives that are targeted at either our training, com-munication, grant payments or whatever

processes help sites be more successful,” said INC’s Macdonald.

Leading CROs also have adopted technol-ogy platforms that helped improve commu-nication with sites and identify potential data problems earlier, which could help reduce the amount of time site staff spend on re-work.

“Pharma companies are counting on CROs to leverage advanced technology and innova-tion to ease the burden on sites and to stream-line processes, in addition to being the face of their company to those sites,” said Paul Colvin, executive vice president, global clinical devel-opment, PPD. “As the environment continues to move toward more complexity and larger trials, and as sites get busier and busier, it is going to be very important that we leverage our technology to make it easier for patients and sites to participate in trials. By using data analytics to identify issues sooner and proac-

tively implementing corrective measures, we can streamline the process, reduce effort both for sites and for patients and reduce costs in the process.”

Susan Romberg, vice president of global clinical development at Chiltern, said ben-efits of strong CRO-site relationships include faster site startup through agreed standards for ethics and contract approvals, clear and efficient monitoring strategies, dedicated li-aisons or project managers that incorporate well-defined communication and escalation pathways, and agreeable and achievable per-formance metrics.

“A close site relationship built around trust, transparency and quality performance can go great lengths to eliminating the friction areas that have existed historically,” said Romberg. “CROs need to become more adept at iden-tifying, supporting and rewarding the top-performing sites. We need to engage in dialog with them on what they need to be successful and look for ways to support that.”

The fact three of the top five CROs—INC Research, PPD and Covance—also were among the top five CROs in the 2013 survey suggests CROs are getting better at creat-ing continuity in management practices and strategies adopted in recent years to improve site relationships are beginning to pay off.

“We figured out quite a while back the importance of site relationships,” said INC Research’s Macdonald. “At the end of the day,

IndustryNews


Attributes for which CROs receive the highest average ratings

Percentage of sites rating ‘excellent’

in 2015


in 2013Ensures timely drug availability 52% 49%

Effectively uses communication technologies (e.g., web portals, IVRS)

51% 48%

Understands local regulatory/ethics issues 50% 47%Has professional medical staff in clinical operations

49% 46%

Maintains open communication 49% 47% Source: CenterWatch; N= 1, 900 sites in 2015; N=2,032 sites in 2013

Highest performing CROs 2015 CROs that received the highest average ‘excellent’ ratings

Attribute rated the most importantHas professional, knowledgeable and well-trained monitors/CRAs

PSI, PPD, INC Research

Is organized and prepared PSI, Medpace, PPD

Ensures timely drug availability PSI, Chiltern, INC ResearchHas easily accessible staff for escalation of issues and provides timely and appropriate resolution

PSI, Chiltern, PPD, INC Research

Has professional medical staff in clinical operations

INC Research, Chiltern, PSI, Medpace, PPD, Quintiles

Source: CenterWatch 2015; N= 1, 900 investigative sites rating CROs on 37 relationship attributes

there are three main pillars of a successful clinical study: a scientifically valid and opera-tionally feasible protocol; motivated investiga-tors who are qualified and appropriate for a particular study; and investigators that have eligible, informed and consented patients to participate in the study.”

As in previous surveys, however, sponsors continue to receive generally higher excel-lent ratings than CROs for site relationship quality. CROs scored two to four percentage points lower than sponsors in each of the six project categories measured. The widest variability between CROs and sponsors was for having professional medical staff in clini-cal operations: 56% of site professionals gave sponsors an excellent rating, compared to only 49% for CROs. Sponsors also received higher ratings for having efficient admin-istrative teams and easily accessible staff. Another notable gap was for providing on-going help in running a study, an individual attribute within the study monitoring sup-port category, for which the positive rating for sponsors was six percentage points higher than that given to CROs.

“It is understandable there is a perception that, as a service provider, a CRO is not as invested or engaged as a sponsor in the out-come of a given trial, but that just isn’t true. Our people are invested, passionate and take great pride and emotion in the outcome of

their work,” said Chiltern’s Romberg. “In fact, referrals from research sites are one of our top sources of new clients.”

Yet Jennifer Selk, co-owner of Florida-based Suncoast Clinical Research, said many sites prefer to work with sponsors directly because, in her experience, they are more knowledgeable about the proto-col, have better defined processes and are more willing to partner with sites in terms of maintaining an open dialogue and com-pensating sites fairly.

“Sites now are more distanced from the sponsors. The CROs often misinterpret the protocol and are unwilling or untimely in escalating questions and concerns to the sponsor,” said Selk. “CROs have to adjust to differing sponsor expectations, so it leads to confusion and things having to be re-done or being done differently from study to study.

There is less confusion and fewer logistical is-sues when dealing directly with the sponsor.”

As the CRO role has changed, however, and sponsors have rapidly transferred site man-agement responsibilities to their CRO part-ners, the overall performance gap between sponsors and CROs has narrowed. The gap between top ratings received by sponsors and CROs has narrowed from 11 percentage points in 2001 to two percentage points this year. CROs and sponsors today operate at near parity in site management, an area that will continue to grow in importance as the in-dustry moves toward risk-based monitoring models that require fewer study monitor visits to sites. The average CRO has made notable improvements in conducting clear study ini-tiation visits and training, for which excellent ratings increased four percentage points dur-ing the past two years, and in using technolo-gy to make processes more efficient, in which excellent ratings increased five percentage points.

“It’s only natural to see that gap narrow because of the increasing reliance on CROs and sites’ deepening relationships with CROs,” said PPD’s Colvin. “From a historic perspective, CROs have come a long way in the past decade. As the industry has ma-tured and focused on how to drive produc-tivity and cost reduction, our sponsors have built much more strategic relationships with CROs. This has led to a much more in-tegrated model, increasing the importance of improved relationships with the clinical sites.”

IndustryNews


Attributes for which CROs receive the lowest average ratings


in 2015


in 2013Provides protocols that require minimal amendments

38% 35%

Is flexible: willing to modify protocols/budgets

39% 34%

Provides prompt payment of grants 39% 36%

Offers realistic grant payment schedules 39% 36%

Has low monitor turnover 40% 34%

Provides adequate funding for patient recruitment

40% 38%

Provides fair overall grant payment amounts 40% 36% Source: CenterWatch; N= 1, 900 sites in 2015; N=2,032 sites in 2013

Average CRO rating across attributes

Source: CenterWatch; N= 1, 900 sites in 2015; N=2,032 sites in 2013

2%2013 2015

4%17%

35%

42%

PoorFair NeutralGoodExcellent

4%13%

36%

45%

2%

IndustryNews

Wide gaps remain in most important areas

Despite improvements, the widest perfor-mance gaps—ranging from 14 to 23 percentage points—remain in critical areas previous Cen-terWatch surveys have identified as the biggest challenges to the quality of CRO-site relation-ships. These areas include providing knowl-edgeable, well-trained monitors; organized and prepared study support; staff easily accessible to solve problems; fair grant payment amounts and prompt payment schedules.

In the widest gap, 71% of sites believe pro-fessional, knowledgeable CRAs are critical to study success, but only 48% of sites gave the average CRO an excellent rating for this at-tribute; this area also had the widest perfor-mance gap in the 2013 survey.

Investigators report CRAs don’t always un-derstand the protocol or lack proper training and create problems for sites when they can’t answer questions or give advice based on incor-rect interpretation of study requirements. Mon-itor turnover also remains a significant problem with only 40% of sites giving the average CRO an excellent mark for this attribute, which was among the lowest ratings in the survey.

“Sadly, we can count on one hand how

many CRAs understood the protocol they were ‘training’ our staff on at the site initiation visit over the last year or 60-plus protocols, which is rather embarrassing and quite a slap in the face when compared to what we are told to do and have training for,” said Jon Ward, CEO of Utah-based Aspen Clinical Research. “Yet the double standard continues.”

Covance’s Johnston believes this area re-mains an industry-wide problem as the mar-ket remains highly competitive for CRAs,

which results in high turnover. The dynam-ics of how clinical trial work is outsourced or where trials are being run at any point in time also leads CRAs to move from one company to another. In addition, cost pressures squeeze the time that some companies are able to spend on individual CRA training.

“It also depends on location and timing. We find in certain locations of a country or region and at specific times it becomes ultra-competitive in that market,” said Johnston. “When there is high demand the supply is low, and when the supply is low it becomes ultra competitive. People at the CRA level are look-ing to expand their careers, their financial gain and their professional development. So they have a tendency to shift from one com-pany to another. But we really see it as a timing issue and it’s generally influenced by location.”

In addition, INC Research’s Macdonald said much of the CRO industry remains func-tionally aligned and allocates CRAs based on availability and, in some instances, proximity to sites rather than therapeutic expertise.

“Our highest criteria in INC is to find CRAs that have the experience and passion to moni-tor in a particular indication. Therefore, when they are on site, they are capable of doing not just the traditional CRA auditing and monitor-ing and source document verification work, but


Attribute category performance

Source: CenterWatch 2015; N= 1, 900 investigative site

Average site rating of CRO ability to provide attributes in the category as 'excellent'Average site rating of sponsor ability to provide attributes in the category as 'excellent'Average site rating of attributes in the category as 'very important'

57%52%

48%55%

54%45%

42%48%

47%45%

53%50%

46%52%

42%40%

49%46%

Contracts and budgets

Work style

Site management

Protocol/Study design and planning

Study monitoring support

Overall project support

Largest CRO performance gaps 2015

Source: CenterWatch 2015; N= 1, 900 investigative sites

Percent of sites rating attribute 'very important'Percent of sites rating CRO ability ‘excellent’

39%52%

40%

42%55%

44%57%

39%53%

40%54%

47%

53%

Sta� is easily accessible

Fair overall grant payment amounts

Prompt grant payments

Realistic project timelines

Uncomplicated CRF design

Adequate funding of patient recruitment

O�ers realistic grant payment schedules

62%48%

68%48%

71%Knowledgeable/well-trained CRAs

Is organized and prepared

IndustryNews

are much more able to collaborate on the issues sites see,” said Macdonald. “You have got to have an expert on site, not a generalist.”

In another area, CROs could improve their relationships with sites, accord-ing to survey results, by having staff eas-ily accessible to answer questions quickly and accurately. CRAs traditionally have been the primary contact for sites, yet the growth of outsourcing has led to a greater number of people involved in a study and investigators often don’t know whom to call with ques-tions. Investigators report having one point of contact assigned to manage the relationship and answer questions about protocol require-ments or payment issues—a practice many leading CROs now employ—can help ensure problems are addressed in a timely manner and build trust.

“The problem lies in the fact that CROs are the ‘middleman’ between the sponsor and the site/Principal Investigator. Many times, days, weeks or sometimes months go by and an out-standing issue, question, concern or clarifica-tion goes unanswered,” said Aspen’s Ward. “We want CROs to be respectful, courteous and timely in their communications.”

As in previous years, budget negotiation and the grant payment process, another respon-sibility many sponsors have handed over to CROs, received some of the lowest scores in the survey. In results and interviews, investigators expressed frustration that negotiation process-es often are slower when a CRO is involved and that their needs often are not communicated to the sponsor. Investigators report a lack of trans-parency in how budgets are determined and payment delays; according to SCRS, in 2014 about 65% of clinical research sites had less than three months of operating cash, an increase from 57% in 2012. More than half of sites rated this category as “very important,” but only 40% of sites gave CROs an excellent rating for per-formance in the contract and budget category.

“My pet peeve is that payments are de-layed,” said Larry Seidman, D.O., president

of Clinical Research of Philadelphia. “When they tell you they will pay you every three months, it’s often every four months. We re-ally have to negotiate to get paid monthly. We have to pay our employees every other week. We need to pay our vendors and are never late. But we can’t afford to carry a big pharmaceuti-cal company or CRO.”

Johnston said delays in grant payments continue to be an industry-wide problem be-cause the data needed to make payments—which include financial, operational and milestone information—often come from disparate systems or processes that must be aggregated manually.

“The systems and the back offices that sup-port grants are not always up with the times. However, many niche grant payment providers have popped up in the last couple of years and they are highlighting a pain point for the indus-try. It continues to be a time for the industry to focus on this and ensure that sites stay whole,” said Johnston. “The investigative sites are go-ing to need to have more timely payments on a more frequent basis. The smaller sites simply can’t absorb the fluctuation in when grants are paid. They are expecting to receive them in a timely manner to pay off their bills. That is still a space where we have opportunity to make significant improvements.”

Looking ahead

Developing strong working relationships with sites will become increasingly impor-tant for CROs moving forward as the indus-try moves toward personalized medicine, for which patient populations will become more scarce and competition for experienced, top-performing investigators will increase. Some investigators and site networks already have begun limiting the number of CROs they work with to only those who will enter a stra-tegic or preferred relationship or those that are easy to work with.

“There is a lot of competition right now for

good sites and that is continuing to increase,” said Covance’s Johnston. “While sites are con-sidered a supplier of a service to us, we believe they need to be treated like a customer, more like an account or an asset rather than just a transaction for the individual study.”

Survey results show top-rated CROs have become better at managing their working relationships with sites during the past two years. Yet, the results also suggest several opportunities for improvement. For CROs to build stronger relationship with sites, they must ensure CRAs are properly trained and understand the protocol; communicate in a respectful, timely manner; offer ad-equate funding for patient recruitment; offer organized study support and improve grant negotiation and payment processes.

“When we have a problem, we want the CRO to go to bat for us with the sponsor, try to help us and have some allegiance to us, just like they do to the sponsor,” said Seidman. “It’s important to keep the Principal Investigator happy. When someone is supporting you, you go the extra mile. When we sign on to a study, we pledge that we are going to work tirelessly to make it successful. And we just want to feel appreciated, and we want to get the backing from the CRO and the sponsor.”

Karyn Korieth has been covering the clinical trials industry for CenterWatch since 2003. Her 30-year journalism career includes work in local news, the healthcare industry and national magazines. Karyn holds a Master’s of Science degree from the Columbia University Graduate School of Journalism. Email [email protected].

Annick Anderson has been conduct-ing 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 [email protected].


april 2015 a special centerwatch feature article reprint ... · the ability to resolve problems...

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