A recently released report details the current status of the clinical trials market in Russia. According to the Russian CRO Synergy Research Group, the Federal Service on Surveillance in Healthcare and Social Development of the Russian Federation (alias RosZdravNadzor, RZN) approved 130 new clinical trials in Russia in first quarter 2008; that's four trials less than in the corresponding period last year. 

The report noted that the main contribution is still made by multinational, multicenter clinical trials. The share of foreign study sponsors in first quarter 2008 stood at 68% of the total number of clinical trials, and 88 new trials were initiated during this period. To read the report from Synergy Research Group, go to 

www.synrgpharm.com/images/SynRG_Orange_Paper_2008Q1_E.pdf

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A recently released report details the current status of the clinical trials market in Russia.

Update on Russia Trials

 (King of Prussia, PA) director of business development–early clinical research, received a promotion to vice president, business development–drug safety assessment (DSA), and will also have spots on the business development leadership team and the DSA management team. 

 (Westmont, IL) found a new senior director of clinical services, Eastern region: 

 as director of business development. Huston previously held the same position with 

 (Leicestershire, UK) Boston, MA, office as vice president, Bridgehead USA. Formerly, Garfield was director of global reimbursement, policy, and economic strategy at 

 (Dublin, Ireland) announced a number of additions to the company. Joining Icon Central Laboratories are 

 as manager of molecular diagnostics and associate director of cellular immunology, research and development, respectively. Additionally, the company's new additions to the pharmacokinetic, pharmacodynamic, modeling, and simulation services area are 

 senior director of pharmacokinetics, pharmacodynamics, modeling, and simulation; and 

 global vice president of pharmacokinetics, pharmacodynamics, modeling, and simulation. 

•  Having been senior vice president with 

 (Lancashire, UK) global client services division, the company promoted three of its employees. 

 will take on the role of global contracts manager, 

 assumes the title of senior project manager, and 

 (Raleigh, NC) Board of Directors and was also selected as the chairman of the INC Research Audit Committee. Furthermore, 

 will serve on INC's Board of Directors as well. 

 (Cleveland, OH) announced a few employment changes. 

 president and chief executive officer of 

 (Lake Bluff, IL), was elected the company's new chairman of the board; 

 assumes the role of interim president; and the position of chief operating office has been eliminated. 

 (Philadelphia, PA) new executive director and global head of medicinal management and safety. Prior to joining Premier Research Group, he established and managed a safety department at 

 (San Francisco, CA). Cheson is now a member of Synarc's Oncology Scientific Advisory Committee, and Juweid is the company's medical director, PET CT. The two men have previously worked together on a critically acclaimed 

 article on the role of PET in cancer treatments, and they also collaborated on a PET-related paper for 

 (Fort Lauderdale, FL). He previously worked as director of research and development informatics at 

 as the company's new president and chief executive officer. Gelenberg also serves as editor-in-chief of the 

Biological Therapies in Psychiatry Newsletter.

 assumes the newly created role of vice president, commercial operations, for 

 (Cincinnati, OH). She will be based out of Crowthorne, UK, at the company's European headquarters. 

 to head up various new divisions and will be responsible for global key account management, corporate marketing, project management, and supply chain management. 

 (Concord, OH) new director of bioanalytical services. 

 (Leicestershire, UK) served as a consultancy firm for 

 (Houston, TX), performing an independent due diligence study for the medical technology company.

 (Bedminster, NJ) created a partnership through Medidata's accredited ASPire to Win program, which allows CROs and other service providers to utilize the EDC solution Medidata Rave.

 (Charlestown, MA) inked an agreement that will allow Icon to offer PHT's LogPad, an electronic patient diary solution, and SitePad Tablet, a site-based data capture product, to its clients. PHT, in turn, will be able to benefit from Icon's Lifecycle Science group's experience with patient reported outcomes research, as well as Icon's Interactive Technologies ICOPhone, an electronic patient reported outcomes product that uses IVR and IWR technology.

 (Princeton, NJ), has formed a consortium with 

 (Quebec, Canada), under which Anapharm will provide Canadian and international companies with clinical development consulting, clinical trial, and laboratory services, and BCF will offer help in the areas of regulatory, quality, and clinical requirements.

 (Kearney, NE) will develop a comprehensive marketing campaign for 

 (Fort Lauderdale, FL) recently announced two new alliances. 

 (Duarte, CA), a National Cancer Institute designated cancer center, will be using OmniComm's EDC solution TrialMaster in their first trial using reusable electronic case report forms developed by OmniComm and City of Hope. Additionally, OmniComm signed a five-year, $8-$10 million agreement with an unnamed, major West Coast biotechnology company, which will use also make use of TrialMaster.

 (Glasgow, UK) will work together to develop their North American markets, and Pii will have access to Bio-Images' clinical and preclinical services.

 (Wayne, PA) chairman and chief executive officer, is a finalist in the 2008 American Business Awards category of Best Chairman.

 (Philadelphia, PA) TrialCheck, an online cancer trial navigation and patient matching service, Best in Show and Best Application for Enhancing Patient Access for Information.

 (Kearney, NE) won three gold and two silver Aster Awards for outstanding health care marketing and advertising.

 (Ontario, Canada) Company of the Year award went to 

 (Alberta, Canada) at the BIO International Convention in San Diego, CA, on June 17.

 (New York, NY) compact, mobile scanner xCAT earned the company a 2008 Medical Design Excellence Award.

 (Tustin, CA) announced the launch of Integrium Clinical Excellence, which, according to the company, is a metric and performance-driven process that enables the on-time and on-budget delivery of sponsor clinical trials.

For the first time, an inspection body for active pharmaceutical ingredients in the European Union—

y (Münster, Germany)—received type A accreditation, certifying that the company is independent, qualified, and competent as an auditor.

 (Boston, MA) released the 2008 edition of State of the Clinical Trials Industry, which boasts more than 600 charts and graphs of clinical trial-related data. Copies of the book run for $699 and can be purchased at https://

 (North Yorkshire, UK), a medical device contract research organization, has created a specialist resourcing division that will place clinical, data management, and regulatory staff so that they can successfully carry out clinical trials for medical devices.

 (North Billerica, MA) recently changed its name to 

 (Nottingham, UK) now offers a research hotel and science concierge service as part of what the company is calling the Biotel, which includes a lab that can be rented by firms or researchers by the day, as well as a nuclear magnetic resonance spectrometer.

The 48th Annual New Clinical Drug Evaluation Unity meeting, held May 27-30 in Phoenix, AZ, provided a venue for 

 (Basking Ridge, NJ) to present five posters dealing with topics ranging from cognition, schizophrenia, depression, and data quality.

 (Cambridge, UK) has received the new MHRA supplementary accreditation for UK Phase 1 units.

 (Hanover, MD), which provides staffing and recruiting services, purchased the scientific division of 

Industry news focusing on the people and organizations who work in the clinical trials profession.

Business and People Update July 2008

• In an attempt to stifle the spread of counterfeit drugs, 

 has called upon intelligence units to catch counterfeiters through means similar to drug trafficking methods. Medical Services Minister Peter Anyang Nyongo said in a statement that his department plans to work with the National Security and Intelligence Services to improve surveillance methods and reduce the number of counterfeit drugs in Kenya, which, according to the country's National Quality Control Laboratories and the Pharmacy Poisons Board, make up about 30% of all drugs circulated throughout Kenya. Similarly, 

 is also looking at pharmacies across the country in an effort to determine the prevalence of counterfeit malaria drugs. 

 amendment may allow pharmaceutical companies to produce lower-cost  generic antiretrovirals, malaria treatments, and other medicines for developing countries. 

 recently approved the first reading of the proposed amendment, which would facilitate the importation of cheaper, generic drugs to developing countries if they cannot manufacture the drugs themselves. Countries that have already approved the amendment are 

Australia, China, the European Union, Japan, South Korea,

 are working in conjunction with researchers at the 

University of KwaZulu-Natal (Durban, South Africa)

 to create a database that could help shorten the diagnostic times of drug-resistant tuberculosis to a mere 48 hours.

Industry news tidbits from around the world.

July Global News

When we last spoke with Peg Regan, president and CEO of PharmaPros, she was discussing the software as a service (SaaS) aspect of data integration within clinical trials. Specifically, the application of PharmaPros' Electronic Data Lifecycle Management (eDLM) approach—a methodology for managing data holistically across a study. 

 Peg Regan, president and CEO of PharmaPros, is redefining eDLM.			

PharmaPros has now taken the next step in addressing what it has termed eDLM by offering Dataflow Manager, launched last month. Dataflow Manager, in the product materials, is described as a comprehensive clinical data tracking and integration framework, with the core function of providing context-aware intelligence of electronic data related to a clinical trial, based on the defined study protocol. What it is in context is a decision support technology leveraging operational intelligence across various disparate source data systems used in conjunction with PharmaPros eDLM based services. 

The Dataflow Manager product, said Regan, is "offering all the knowledge of our company." 

With all that internal brain power captured and eDLM defined, Regan and the PharmaPros team are now left with establishing the education and vocabulary around eDLM. "Coming up with the right vocabulary around eDLM is challenging," said Regan. "This is a new concept, a level of data intelligence that hasn't been accessible before." 

The data intelligence that is currently being left to squander is a result of the data integration issues that Dataflow Manager addresses. Specifically, the increasing number of data sources incoming to the sponsor and how data is stored in vertical data warehouses or silos. Data sources include EDC, ePRO, IVRS, CTMS, and lab data—all from differing vendors, using different software and processes. 

"There is a need for the sponsor to stay on top of the trial and the data and to respond to issues proactively," explained Regan. "In a holistic manner, where are we in the trial?" Because of the proliferation of technologies, there is a lack of visibility into the overall progress of a trial. If the trial were viewed as a whole, there would be more value to all the constituents conducting the trial. The ability to view data holistically could positively impact many aspects of clinical trials, including adaptive trial design, milestones, and safety signaling throughout the trial. "However, it is nearly impossible to do that until all the data is put back together," said Regan, which is the current state of affairs. 

For William Tobin, president of Norwalk, CT-based International HealthCare (IHC), a full-service CRO with about half of its employees in data monitoring, using eDLM has changed the way they view and use data. Previously, the staff relied solely on its proprietary Excel-based system. In 2003, Tobin discussed with PharmaPros the ways they could use additional tools for data flow. The outcome was an eDLM solution that featured the continued use of the Excel proprietary system but with a more dynamic integrated database. 

"The big thing that we're using in our system is tracking our monitoring visits," said Tobin. "But we didn't have a data snapshot of how many subject visits we should have each visit. With Dataflow Manager, the monitors know more of what is expected from their site visits." Translated, it means instead of the client mandating a routine every eight week site visit, IHC can look to the Dataflow Manager to determine when the site will have collected most of the data and the most optimum time to visit the site. "It has reduced travel by at least 100 visits," related Tobin, and increased efficiency by 20% to 30%. 

Elizabeth LaFrance, project manager of clinical operations for Tempe, AZ-based biotech OrthoLogic Corp., told 

, "You can use Excel spreadsheets, but it won't give you the knowledge that you can get from this holistic view." Using an earlier version of Dataflow Manager in a rescue trial, LaFrance was able to track visits, CRF forms, and know what was expected and what was delivered from each site. 

"When we reach Phase II with our current drug, there will be samples, photos, IWRS, and information from multiple vendors that we will be able to pull in one place and manage proactively," said LaFrance. And, that is what Regan means when she says that the data holds the intelligence of the trial.

PharmaPros Takes Electronic Data Lifecycle Management to a New Level with Dataflow Manager.

Where's the Trial Data

Clinical research sites across the country continue to struggle with managing their economic reality. Recent data indicates that many hard working clinical research sites are not operating on a financial break-even basis.

  Losing money may be a significant reason why many health care institutions and principal investigators are terminating their clinical research programs. 

( Photography: Getty Images    Illustration: Paul A. Belci) 

Statistics show that for every two new physicians engaging in research practice this year, 1.5 will give it up within two years.

  According to the Tufts Center for the Study of Drug Development, the number of principal investigators conducting industry sponsored clinical studies in the United States has declined 11% since 2001. "By 2000, half of all principal investigators in the United States chose never to conduct another clinical trial—nearly double the turnover rate observed 10 years before."

Compounding these challenges is the continued 20-year transition of clinical research projects into private medical practices. Nearly two-thirds of all studies are placed in community-based, for profit investigative sites.

  Private practices are unable and unwilling to sustain nonessential endeavors that continue to lose money. To ensure the perpetuity of clinical research programs, there is a need for diligent financial monitoring and reporting. 

Table 1: These important measures do not help forecast future financial results. 

The topic of financial reporting for clinical research sites is large and overwhelming. Principal investigators and their research team members become involved in research for various reasons, including scientific interest, access to state-of-the-art therapies, and a passion for improving patient care. Few of these research professionals decided to pursue clinical research purely for financial gain. This situation has resulted in a message frequently heard from sites across the country concerning the need for an economic measure of their current financial success. 

Table 2: An example of a simple ASRI calculation. 

Many sophisticated research sites develop complex annual budgets; however, this one-time process does not measure the ongoing success (or failure) of the research site. Stated in a different manner, research sites need a Dow-Jones indicator that evaluates their real-time performance. This site-based research indicator needs to be accurate, intuitive, useful, and easy to calculate. The purpose of this article is to share a research indicator that sites can use throughout the year to answer the important question posed by principal investigators and executive managers nationwide: "How are we doing?" 

Let's consider the need for a real-time research performance indicator by reviewing the popular Dow Jones Index. The Dow Jones Index Average (DJIA) is one of the most widely followed financial indicators in the world. The DJIA appears in newspapers, throughout the day on TV, and in real-time on many financial and consumer Web sites. The DJIA represents a collection of 30 internationally recognized blue chip stocks. While there are many alternatives, the DJIA is still the index we instinctively check first to see how the market is doing.

  At any given point, there are approximately 10,000 stocks in the United States.

The quantitative value of this relatively limited index of 30 companies is debatable. However, the relevance of the DJIA to most consumers is the correlative value and learned associated meaning. There is a correlation between the DJIA and the value of most retirement stock holdings. In other words, when the Dow Jones is up, many 401(k) mutual funds are also up. When the Dow is down significantly, it is understood that the value of most retirement holdings has been reduced. Investors and consumers have learned the association between the DJIA and many financial investments. Clinical research sites need a similar performance metric that can be easily reviewed on a regular basis. 

Figure 1. With the use of ASRI, this research team has tracked their monthly enrollment goals and knows exactly how much more is needed to meet their annual financial goal of $540,000 by the end of the year. 

Clinical research sites need to make an important financial assessment and decision when reviewing new study opportunities and their respective budgets. The acceptance of a proposed trial budget represents a significant long-term investment decision. Comprehensive management of a clinical research program includes making the appropriate study selection decision; however, a site also needs to conduct consistent reviews of relevant ongoing performance measures. 

Many advanced clinical research managers construct and regularly publish performance reports, status reports or key indicator reports. These important analyses are designed to investigate and evaluate the work completed by the clinical research team. Unfortunately, most of the key indicators included in these reports have limited correlative value with the long-term financial performance of research sites. These backward-looking indicators reflect the work completed at the site; they do not accurately forecast the future financial success of the research program. Table 1 includes a review of many commonly reported clinical research site status indicators. 

Most commonly reported performance measures contain a review of historical work completed—many have no financial basis. These interesting and important data points are unable to assist the clinical research professional in forecasting the future financial results of their program. The limitations of these measures and the need for a more accurate metric have resulted in the development of a new performance indicator: the Andrew Snyder Research Index (ASRI). This research index is based on the latest management accounting and executive dashboard academic lessons.

  It is easily calculated and includes a blend of several commonly reported site performance measures. 

The ASRI is defined as the contractual value of subjects enrolled. The value can be computed over any period of time. Here is the formula: 

ASRI = Sum [Contractual Value Per Subject x Number of Subjects Enrolled]

ASRI builds upon the most commonly published status report metric (i.e., the number of subjects enrolled) to develop a financial forecast for your research program. It recognizes the successful enrollment of a subject as a future revenue stream. Regardless of the amount of work required or the length of subject participation, enrollment of a research subject represents the contractually and legally defined beginning of a future revenue opportunity. Upon enrollment, your research team will implement the clinical trial protocol with the subject. You will be financially compensated for this service according to the terms of the contract. The ASRI converts your success in enrolling subjects into a quantitative future revenue analysis. 

Analyzing the sum of all future revenue opportunities will provide your research team with a useful financial forecasting tool. The example displayed in Table 2 provides a simple review of the ASRI calculation. This example demonstrates a research team that is managing three enrolling clinical trials. The contractual per subject value of the studies ranges between $250 and $7500. This research team split their efforts between the three trials and successfully enrolled 27 subjects. 

The ASRI provides a considerable amount of information to interested coordinators, site managers, principal investigators, and executive management. It also can be an accurate indicator of future revenue performance. 

The ASRI normalizes many research data points into financial terms and provides a relevant assessment of revenue opportunity. It does not indicate precisely when the subject revenue will be recognized, but simply illustrates the relative value of all subjects enrolled. The ASRI is relatively accurate due to the inclusion of specific trial information and real-time enrollment values. It does not use rule-of-thumb study heuristics—the calculation relies upon your detailed study budget information and actual subject enrollment results. As a quick-and-easy financial forecasting tool, the ASRI provides a projection of research program revenue results. 

One of the primary benefits of the DJIA is the correlative value of the financial indicator: as the Dow goes up, many retirement holdings are likely increasing in value. The strength of the ASRI is the correlation between it and the fiscal year-end revenue results experienced by research programs. By definition, as the ASRI increases, the revenue stream (and year-end financial results) will also increase. The ASRI is not a substitute for a thorough budgeting process. Moreover, it is most valuable when used in conjunction with a detailed enrollment forecast. 

Here is an example of how it works. A research program's annual revenue goal may indicate that the research program must enroll subjects totaling $1.2 million in financial value while participating in a number of various trials. The ASRI would indicate that you must enroll $100,000 worth of subjects each month. If the ASRI result for one month is only $50,000, the site will immediately realize they are significantly behind schedule. The ASRI correlates very closely with the research programs ability to meet their financial goals. 

The ASRI correlates directly with revenue forecasts; however, it can also be compared to research program expenses. For many clinical research teams, fixed expenses may represent 80% to 90% of their total annual expenses. Expense categories such as salary support, rent, and overhead do not change with enrollment results. Research sponsors provide most of the study's medical, clinical, and administrative supplies. As such, the variable expenses typically represent a relatively small fraction of the research program's annual budget.

  Following this logic, the ASRI can provide the site manager with a quick and easy profitability indicator. 

Consider the following example. A research site forecasts $550,000 of annual fixed expenses for staffing, overhead, etc., and another $50,000 of variable expenses for hospital procedures for a total projected expense budget of $600,000. In this example, the site needs to enroll at a financial rate of $50,000 per month in order to break even. If the site only enrolls $25,000 worth of patients in a particular month, they will have to make up the difference in the following month in order to maintain pace with their expenses. 

For site managers, the most important characteristic of the ASRI analysis tool is its ability to intuitively convey a complex amount of information to a wide variety of interested stakeholders. The ASRI performance metric can provide principal investigators, executive management, and research team members with an assessment of their long-term performance. A monthly status report may contain many relevant metrics, but physician stakeholders appreciate the value of this Dow Jones-like research indicator and its statistical correlation with their research program's financial success. Additionally, this data point is reported by some of the more advanced clinical trial management systems; in this case, the ASRI is immediately available at anytime. 

Figure 1 provides an example of a research program with an annual budget of $540,000. This research team needs to enroll at a rate of $45,000 worth of patients per month in order to meet the financial goal. This example illustrates a fairly typical research team that has experienced several months of busy enrollment and a few months in which their enrollment efforts were less productive. In either case, this research team is tracking their success on a monthly basis against their stated goal ($45,000 of enrollment value per month). This evaluation process provides the research program with a tool to make strategic decisions based on quantitative performance data. As you can see, the research site needs to enroll at a higher rate in December to meet their financial goals. The site can monitor the trend of the research index and make operational changes throughout the year. If the research index is below budget, the site could shift staff between studies and pursue financially viable trials with a positive enrollment trend. 

The ASRI combines several types of information into one performance metric. This status measure normalizes data that might otherwise confuse the issue. It doesn't matter how long studies run, it doesn't matter how many subjects are enrolled in any particular study or even that a favored study closed early. Research sites recognize the reality that clinical research is a volume-based industry. To remain financially viable, sites need to consistently enroll patients over the long term. The ASRI is designed to measure this enrollment success and provide research centers with real-time information to make important staffing, study selection, and strategic decisions. 

The ASRI is a performance indicator designed to evaluate the long-term performance of clinical research team activities. It cannot be directly converted to revenue or cash budget forecasts. Remember the Dow Jones. You cannot link the DJIA performance directly to your financial worth. The DJIA is simply an indicator of the financial market's direction. 

The ASRI is an indicator of research program enrollment and revenue direction. It is a pure financial performance metric. This financial measure does not evaluate the work required to complete the enrollment and provide care for your research subjects. It also does not allow for subjects that withdraw or discontinue. Sites that participate in studies with high drop out rates need to adjust their ASRI goals accordingly. 

Clinical research sites continue to struggle with the financial pressures associated with managing clinical research protocols. Sophisticated clinical research sites are able to develop annual research budgets; however, there is a need for an easily calculated financial performance indicator that illustrates and forecasts the research site's economic performance. The ASRI is an accurate, correlative, and comparative status metric that combines financial information and enrollment results to provide intuitive information to research stakeholders. Consistent utilization of the ASRI will assist research teams in managing their strategic goals and answering the question: How are we doing? 

MBA, FACMPE, is a faculty member at Metropolitan State University and director of research finance at the St. Paul Heart Clinic, 225 N. Smith Avenue, Suite 500, St. Paul, MN 55102, email: 

1. A. Snyder, "Clinical Research; Value to the Medical Practice and Identification of Best Practices," American College of Medical Practice Executives—Medical Group Management Association, August 2004. 

2. W. Henderson, "Clinical Research in the Private Medical Practice," American College of Medical Practice Executives—Medical Group Management Association, September 2002. 

3. Tufts Center for the Study of Drug Development, "Number of Principal Investigators in the U.S. is Declining,"  

www.csdd.tufts.edu/newsevents/recentnews.asp?newsid=54

4. K. Getz, "Industry Trials Poised to Win Back Academia," 

www.djindexes.com/mdsidx/index.cfm?event=showAvgBenefits

6. J. Zweig, "How Many Stocks Should You Own?" CNN Money, 

www.money.cnn.com/2007/09/06/pf/zweig_september.moneymag/index.htm

7. R. Kaplan and N. Inamdar, "Applying the Balanced Scorecard in Healthcare Provider Organizations," 

Feature Article

Real-time financial performance indicator for clinical research sites that answers the question, how are we doing?

A Dow Jones for Sites

The EU Clinical Trials Directive has garnered much criticism since its implementation in 2004. Many clinical research professionals feel that the Directive—created to improve patient protection, harmonize European clinical trials, and boost the quality of research—has hindered progress instead of aiding it. 

 Sample page from the ICREL survey designed specifically for commercial sponsors who conduct trials in the EU. 

Thus, in an attempt to analyze the impact of the Directive, a consortium created by the European Forum for Good Clinical Practice (EFGCP) and comprised of the European Clinical Research Infrastructure Network (ECRIN), the European Organization for Research and Treatment of Cancer (EORTC), Ethics Committee of the Medical University of Vienna, and Hospital Clinic I de Barcelona, established the Impact on Clinical Research of European Legislation (ICREL), a one-year project stemming from DG Research's desire to acquire data on the effects of the Directive. 

On May 30, 2008, ICREL launched an online survey that allows stakeholders to share their experiences with the Directive. The data collected through the survey will provide a basis for objective analysis of the Directive's consequences in all aspects of clinical research and will allow for the ICREL project members to identify areas for improvement. 

"ICREL is not only supposed to give data but also examples of best practices," said Ingrid Klingmann, ICREL project coordinator and EFGCP member, to 

. "By participating with their information, stakeholders have a unique chance to demonstrate the problematic areas to the European Commission and have a means to encourage change in direction of their interests." 

There are four variations of the survey—formulated by groups called Work Packages, which organized the project—based on stakeholder category (commercial sponsor, noncommercial sponsor, ethics committee, competent authority) as the Directive's impact varies among different stakeholders. 

"We were very clear from the beginning that all stakeholders in the clinical research process needed to be included," explained Klingmann. "The only group we have not involved with a dedicated questionnaire are patient organizations. But their issues are included in the Work Package Ethics committees and are dealt with in nonstructured surveys and interviews." 

The Work Packages ensured that each survey was tailor made to deal with distinct topics the various stakeholders encounter while working within the Directive's framework. The stakeholders can use the questionnaires to weigh in on the difficulties such topics have caused for them and propose ways in which they can be changed for the better. 

"ICREL is not intending to improve anything but to give objective information," Klingmann clarified. "With the selection of the stakeholders and acceptance of the project plan by the European Commission when they awarded the project to our consortium, there is an implication that these areas are open for discussion on the need for change." 

For the project to have any real effect, however, ICREL needs as much input as possible. Aside from spreading the word through mailings to the consortium members' databases, giving interviews, and displaying their material at industry events, they have been publicizing the surveys by asking organizations to link to it from their Web sites and send out mailings. The survey will be accessible through July 20, and the results will be compiled and used in conjunction with earlier surveys, existing databases, and information from publications that also examined the effect of the Directive. The findings will be discussed at a conference in Brussels, Belgium, on December 2, 2008. 

ICREL encourages anyone affected by the Directive to complete the survey. To do so, please visit 

Online survey allows clinical research professionals to share their experiences with the European Clinical Trials Directive.

ICREL Assesses EU Trials Directive

Subject recruitment continues to be an integral part of the drug approval process and is the number one cause of trial delays. The total cost per subject for a Phase III study exceeds $26,000, according to Cutting Edge Information. These experts say the average cost to reach and recruit subjects for a research study is approximately $7600 per subject. In the subject recruitment category alone, pharmaceutical and biotechnology companies have allowed an 86% failure rate—a rate that would not be tolerated in any other industry.

Pharmaceutical and biotechnology executives rank subject recruitment as the most costly and time consuming aspect of clinical trials, yet many companies fail to take proactive steps to develop a strategic plan and specific budget for subject enrollment before the start of a research study. A few key components directly affect the enrollment rate: the protocol criteria, the research sites, and recruitment planning. The industry must do a better job of identifying enrollment obstacles and use strategic tactics and budgets in the initial planning process to assist in recruitment efforts and control costs. 

Planning and budgeting before the study starts is much easier and less expensive than going back after the study is behind schedule. In a rescue situation, media costs are at a premium, with little or no time for planning and negotiation of rates. Top dollar must be paid. In addition, trial sponsors continue to pay associated internal and external study costs, including investigator fees, CRO fees, and internal personnel salaries. 

In most cases, without a proactive plan, dollars have already been wasted on advertising and materials that did not work at the site level. Sponsors often allocate a lump sump dollar amount per site to be spent on media advertising and materials. This is not the most cost-effective use of recruitment budgets. 

Media costs vary widely by market. For example, a newspaper ad in Dallas, TX, sells for $2500. The same ad costs $800 in Louisville, KY. A planned media campaign with the right tactics to reach the target audience is imperative. 

Creative development of branded, cohesive study materials that motivate patients to respond is also key to successful subject recruitment. Consistent materials increase brand awareness and recall among potential subjects. The combination of these marketing efforts and site databases will help enroll the study on time. 

Of course, advertising creative development and media buying are not the study site's specialty. The site staff's time is best utilized when devoted to screening and enrolling subjects and managing the clinical study. 

Millions of dollars per day are lost due to delays in the drug development process. The industry is under tremendous pressure to streamline costs.  Studies show that pharmaceutical companies that successfully reduce the drug development cycle time use proactive strategies that include subject recruitment programs. 

Proper planning that includes careful analysis of the protocol, target audience, and market research will result in a recruitment strategy and budget that can be established up front to help manage costs and enroll the study on time. 

Clinical trial sponsors will pay for subject recruitment. The question is simply: How much and when?  

 is vice president of operations at Praxis

A Closing Thought

The impact of proactive subject recruitment planning.

Remembering Recruitment

Cordium Links, a provider of centralized cardiac safety monitoring, announced that it has established a joint venture with a Chinese organization to deliver core lab services to drug development companies performing cardiac safety evaluation as part of clinical research in China. The joint venture is called Lawke Links. It aims to bring a full range of ECG core lab services, including project management, site support, and centralized ECG data analysis to China. Lawke Links will provide FDA- and ICH-compliant cardiac safety analysis to biopharm companies conducting Phase I–IV multinational trials. 

Lawke Links will donate 9% of the value of work performed on all of its contracts through June 2009 to support the reconstruction and humanitarian efforts associated with the recent earthquake that devastated the country. 

In addition to ECG core lab services, Lawke Links has established an exclusive relationship with Peking Union Lawke Biomedical Development Limited (PUL) to provide central lab services. Jian Ho, MD, PhD, chief executive officer and medical director at PUL, will initially head up project management and site support for Lawke Links in China. "It's an honor to bring the resources of one of the leading core labs in the world to China," said Dr. Ho in a press release. "We will be the first and only lab that provides a full range of core lab and central lab services to the growing Chinese market." 

China represents one of the world's fastest growing markets for clinical trials.  According to the Tufts Center for Drug Development, the market for clinical trials in China has grown 43% in the past three years. 

Lawke Links will offer all the advanced services that Cordium Links provides its U.S. customers, including 12-lead digital ECG, Holter monitoring, centralized data management, and QT/QTc analysis and reporting. As an "in country" core lab, Lawke Links hopes to eliminate the difficulty sponsors currently face in sending equipment and locating expertise for trials conducted in China. According to Cordium Links, ECG core labs that currently support trials in China typically send equipment and technical expertise, which adds time and expense. In addition, sponsors often must pay for the use of equipment shipped to China until it is returned.

Lawke Links, Cordium Links new joint venture with a Chinese organization, will bring a full range of ECG core lab services to China.

Joint Lab Venture Targets China

Project Phidisa is a clinical research project focused on the management and treatment of HIV infection in the uniformed members of the South African National Defence Force (SANDF) and their dependents. This is a joint research collaboration between the SANDF, the United States Department of Defense, the United States Department of Health and Human Services, the National Institutes of Health, and the National Institute of Allergy and Infectious Diseases. The project currently encompasses an epidemiology study for HIV positive or negative individuals and a treatment protocol for individuals infected with AIDS. 

 (Photography: Getty Images    Illustration: Paul A. Belci) 

In accordance with the Guidelines for Good Practice in the Conduct of Clinical Trials in Human Participants in South Africa,

  clinical research monitors are appointed by the trial sponsor to perform quality assurance activities related to the conduct of the trial. As such, any noncompliance with the protocol, standard operating procedures (SOPs) or applicable regulations should be communicated to the study team and remedied immediately. The sponsor is obligated to terminate the participation of an investigator and/or site if persistent noncompliance is noted. 

To evaluate site compliance, a matrix of performance measures (benchmarks) was established for Project Phidisa in July 2005. These benchmarks are a tool for members of the Phidisa Project to prioritize and review the outcomes of the current compliance assessments and to evaluate any interventions that were implemented to decrease noncompliance. Evaluating clinical site performance based on the benchmark tool has had many benefits, though limitations of the tool have also been realized. 

Table 1. Parameters are measured against a target standard. 

Benchmarking has become a popular mechanism in the business community to increase performance by evaluating internal practices and measuring them against standards set as performance metrics. Business executives have realized the benefits of a metrics-based approach to evaluate the performance of operations in order to maximize productivity. Performance metrics provide a numerical standard against which critical values can be compared. Over the past several years, this tool has been adopted by the clinical research industry with the goal of maximizing site performance. 

Although only a few articles have been published on this topic, much of the literature that exists focuses on laboratory selection,

  site selection, and site maintenance. Several clinical research organizations (CROs) have used this tool to allocate site payments, as they are determined by evaluation of performance metrics. 

One research study outlined the use of benchmarking clinical trials in Central and Eastern Europe.

  This research evaluated site benchmarking analyses as related to speed (number of days to obtain review approvals to the first subject visit), quantity (number of subjects a site can enroll), and quality (number of queries per case report form [CRF]). The study concluded that benchmarking provided an effective tool for improving data quality, reducing time to market, and realizing a decline in development costs. 

The Phidisa Project is a government-sponsored trial that does not seek to market a particular drug. The primary aims of benchmarking in this setting are to improve data quality and increase subject safety. The benchmarking strategy in this project is designed to establish site goals, identify areas for improvement, highlight achievements, and utilize information to drive process enhancements.  

In accordance with Phidisa protocols and regulatory requirements, Phidisa active sites are monitored at regular intervals. During routine monitoring visits, recorded data is reviewed and validated, processes implemented at sites are assessed, and protocol compliance and adherence to regulatory requirements are evaluated. Findings are documented in a monitoring report and submitted to the sponsor through the regulatory department. 

Monitoring findings, which could potentially impact the conduct of the study and outcomes, were noted during the first two years of the Phidisa Project. These findings related to:  

Clinic processes and administrative issues: management of patient files and source documents

Study conduct: eligibility assessment, informed consent, and reporting of reportable events

Subject management: management and follow-up of underlying conditions, co-infections, and psychosocial support

Subject follow-up: management of missed follow-up visits

Staff issues: sufficient resource and distribution of workload.

Monitoring reports were detailed but lacked a quantitative assessment of site performance. In addition, as the study progressed and sites were added, quantitative assessments were needed to ensure that key protocol activities were being performed according to comparable standards across all sites. Therefore, based on monitoring findings, regulatory requirements, and GCP fundamentals, the benchmark assessment tool was developed. It consists of 12 parameters that can be evaluated and reported quantitatively, and each parameter is measured against a target standard as shown in Table 1. 

Benchmark assessments are completed during each monitoring visit, tabulated, reported to the clinical site team during the exit meeting, and commented on in the final monitoring visit report. Benchmarks are assessed as follows:  

. The number of new informed consent forms (ICFs) completed correctly (according to protocol, Phidisa SOPs, and GCP requirements) is compared to the total number of new ICFs obtained since the last monitoring visit.

. The number of protocol violations properly reported by the site is compared to those found while reviewing the CRFs and source data during the monitoring visit.

. The number of properly reported adverse events (AEs) and serious adverse events (SAEs)  compared to those found while reviewing the CRFs and source data during the monitoring visit.

. The number of properly reported study endpoints (reported on the same CRF page) compared to those found while reviewing the CRFs and source data during the monitoring visit.

. The number of CRFs received by data management (DM) as compared to the number of CRFs expected (according to visit schedules). This is determined by DM.

. Pharmacy drug accountability records are compared to actual drug counts for 23 antiretrovirals dispensed to participants. Details of discrepancies are given to pharmacy staff and clarifications taken into consideration before the benchmark is finalized.

Action on critical alert laboratory findings

How one research project in South Africa developed its own benchmark assessment tool to gauge performance and compliance across sites.

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