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Apart from training and certifying individual EC members, the Dutch Central Committee on Research involving Human Subjects (CCMO) recently added training of investigators to its repertoire.  

On December 3, 2012, at the Academic Medical Center Amsterdam, Prof. dr. Marcel Levi opened the eLearning website Onderzoekswijs.nl. "Clinical Research in our country is still standing strong, as compared to other EU countries. The number of trials taking place in the Netherlands this year is even a bit higher as compared to last year," Levi said. Of all trials performed in the Netherlands, more than 40% are categorized as "investigator-initiated," a number which has remained quite stable over the last few years. 

The free-to-use modules, that were designed on the basis of frequently asked questions from the field, offer no examination. However, after the instructions, a user may test his/her knowledge gained by answering a few questions, with direct feedback. Currently six themes are covered:  					

Four of the six start off with a video fragment. More modules may be added. In principle, the eLearning is intended for those interested/involved in investigator-initiated trials. However, any investigator may benefit from its contents. 

CCMO anticipates the eLearning modules will soon be used in the compulsory training by all eight Dutch University Medical Centers.  

The website's slogan is "Test and Increase Your Knowledge" with the language used in the eLearning modules being Dutch. Further information can be obtained from 

News

Apart from training and certifying individual EC members, the Dutch Central Committee on Research involving Human Subjects (CCMO) recently added training of investigators to its repertoire.

Free-to-Use eLearning Modules

Clinical development programs in the biopharmaceutical industry have become increasingly complex and continue to do so. In view of strong competition for productive sites; cost and time constraints; challenging internal and external environments; and large multinational stakeholder teams, the skill set of a clinical project leader is nowadays a key success factor. Executive clinical project leaders are involved in development programs encompassing a range of highly complex clinical trials. The key operational challenge of these programs are Phase III clinical trials involving hundreds of investigational sites and thousands of patients across different regions, cultures, healthcare systems, and regulatory environments. How can it be ensured that all contributors to the clinical trial production chain work properly on time, within expected scope, and on budget? One of the major obstacles still appears to be missing effective leadership at the project level.

What are the three most important interpersonal characteristics (soft skills) of a successful/ideal project leader? The authors addressed this question to the clinical research professionals attending the regional chapter meetings, organized by the German Society of Pharmaceutical Medicine (DGPharMed) in Mannheim, Hamburg, and Berlin between February and September 2011. The survey results are presented and discussed in this article.

	The survey was conducted among the clinical research professionals who attended the regional DGPharMed workshops entitled Project Management in Clinical Research held in Germany in 2011. The attendees heard about the principles of project management as applied to the conduct of clinical trials. The vast majority of participants then took part in the survey and selected the three most important characteristics of a successful/ideal project leader and rated these characteristics as most, second, and third most important. The meaning of the term project leader was explained to the respondents as a clinical project manager, study manager, or similarly named function with the responsibility to manage and primarily lead the clinical trial, project, or program depending on the size of the organization and the applicable settings. A skill set differentiation between clinical project leadership and clinical project management was not conveyed.

	The multiple-choice questionnaire offered the following pre-defined characteristics without further definition of terms: long-term experience in clinical research, risk awareness, medical expertise, knowledge of drug development, innovative, confidence-building, dependability, effective communication, clear goals, and proactive working style. The authors pre-selected these characteristics based on results of a Drug Information Association (DIA) tutorial attended by Schenk-prior to the DIA Conference entitled The Future of Pharmaceutical Project Management, Weston, Florida, November 13-14, 2007-where the participants (N=15) identified the three most important personal characteristics of an ideal project leader without any pre-defined answers.

	In the 2011 survey, a free text option allowed for the addition of further characteristics. To rule out any influence by the order of pre-defined answers, the last workshop (23% of participants) utilized the questionnaires with a changed sequence of the characteristics displayed in the questionnaire forms. The order of options on that finally used form was selected on a random basis.

	A total of 226 out of 235 clinical research professionals attending the workshops participated in this survey. Fifty-nine (26%) respondents represented pharmaceutical companies (mid-size to global pharma), 124 (55%) were from CROs, and 43 respondents (19%) worked in other organizations including biotech and medical institutions, or were freelance professionals.

	As illustrated in Figure 1 the majority of participants worked in project or study management (122; 54%), followed by trial monitoring (28; 12%). Clinical research and development functions (both non-medical and medical) were underrepresented in this survey (5% and 7% respectively). Twelve percent of respondents worked in trial monitoring or trial assistance functions. Only 2% of all participants had a data management role. Forty-four (20%) participants worked in other functions not listed above including freelance professionals, investigational sites, or SMO personnel and other functions. The distribution of participants by function and organizational affiliation was similar across all three regional workshops.

	The majority of project and study managers worked in CROs (20% and 13% of all respondents, respectively). Pharmaceutical companies were represented mostly by the study management functions (10% of all participants).

	The overall results of the survey are displayed in Figure 2. They demonstrate that 44% of participants rated effective communication as the most important characteristic of a successful/ideal project leader and 38% rated it second most important, followed by having "clear goals" (34% rated as most important). A proactive working style arrived on rank 3 (rated by 23% as third most important). Thus, 82% of participants identified effective communication as either the most or second most important factor. Overall, besides effective communication, clear goals and a proactive working style were the most frequently selected categories.

	The subgroup analyses by organization (Figures 3 and 4) and function did not reveal obvious differences in the results. Effective communication was the key characteristic rated by all analyzed subgroups as either the most or second most important characteristic.

	Representatives of pharmaceutical companies consistently rated effective communication (rated by 42% as most important, and by 36% as second most important), clear goals (rated by 31% as most important and by 29% as second) and proactive working style (rated by 32% as third most important) as the most important characteristics. Additionally, they rated dependability (rated by 12% as third most important) and long-term experience in clinical research (rated by 10% as third most important) of considerable importance (Figure 3).

	Contrary to pharmaceutical companies, CROs (Figure 4) valued risk awareness (rated by 16% as third most important) and dependability (rated by 15% as third) as one of the most important characteristics in addition to effective communication (rated by 48% as most important and by 38% as second), clear goals (rated by 34% as most important and by 23% as second) and proactive working style (rated by 22% as third most important). The value of a proactive working style was slightly lower rated by representatives of CROs as compared to pharmaceutical companies (22% versus 32% rated as third most important by CROs versus pharmaceutical companies).

	Fifty-three percent (i.e., 8 of 15) of representatives of the research and development medical functions from both CROs and pharmaceutical companies rated clear goals as the most important characteristic. Of notice is that the majority of respondents in this group selected effective communication as second most important characteristic only (rated by 20% as most important and 53% rated as second). This group valued the knowledge of drug development (20% rated third) and proactivity (20% rated third) that appeared to be higher as compared to other function subgroups.

	The overall results of the research and development function subgroup (both medical and non-medical functions) showed similar results defining clear goals (rated by 48% as most important) and effective communication (rated by 52% as second) to be at the top. A proactive working style (rated by 33% as third) and knowledge of drug development (rated by 19% as third) were on rank 3 and 4 of this subgroup.

	For the project and study management functions, effective communication was either the most or second most important characteristic (rated by 49% as most important, and by 36% as second), followed by clear goals (34% rated as most important and 27% as second). Risk awareness and dependability as the third most important characteristic were rated in 16% of cases reflecting the focus on risk management and trust in this subgroup of functions.

	As shown by different subgroup analyses, effective communication, clear goals, and proactive working style were considered to be the most important characteristics of a successful project leader. Knowledge of drug development, risk awareness, and reliability were rated as second most important by some of the subgroups in addition to communication, clear goals, and proactive working style. None of the subgroups and a very limited number of all respondents assigned a high value to long-term experience in clinical research, confidence-building personal skills, innovative behavior, as well as medical expertise.

	A number of educational textbooks on project management describe effective leadership as an essential prerequisite for project success. These textbooks provide comprehensive lists of project leader skills and competencies. While many sources provide representative data on technical skills, only limited data is available to characterize and evaluate the importance and role of personal/soft skills of successful project leaders. Most often this data is based on opinions of a limited number of project leaders and not based on large empirical research and representative surveys.

	Overall, only few investigations have been conducted to date to characterize the most important soft skills of successful project leaders, and a limited number of basic research studies has been performed so far, particularly in the pharmaceutical development sector.

	Aitken and Crawford16 evaluated the core set of behaviors of superior project managers (n=41). The essential behavioral competencies included delivering results and meeting customer expectations, planning and organizing, deciding and initiating action, leading and supervising, as well as persuading and influencing. Personality characteristics were consistent in rating as compared to behavioral competencies and included conscientious, vigorous, controlling, socially confident, evaluative, and persuasive. Of notice is that none of those characteristics specifically identified highly-developed communication skills as such as an essential competency.

	Skulmoski and Hartman described different competencies across all phases of the project based on 33 qualitative interviews conducted with 22 information systems project managers in Calgary, Canada. Communication competencies were identified as most critical during initiation, planning and closeout phases of a project.

	According to different sources communication or part of the skills related to communication are described as important or highly important. Thus, one of the critical skills that typically differentiates a project leader from a technologist is the ability to communicate well, both orally and in writing.

	The US DIA tutorial that induced the European survey presented in this article identified a proactive working style (47%, n=7), clear goals (33%, n=5) and effective communication (33%, n=5) as the personal characteristics of a successful project leader across the 15 respondents representing primarily the pharmaceutical industry

 who each was entitled to a maximum of three responses.

	In this survey, a large European panel (n=226) with experience in or exposure to project leadership in clinical trials confirmed the results obtained in the small US sample with effective communication assuming rank 1 ahead of clear goals and a proactive working style.

	The authors acknowledge the survey limitations due to restriction to soft skills of a project leader. Hard skills including education and expertise in the specific therapeutic area of project leaders have intentionally been disregarded. However, these types of skills are by all means considered to be a prerequisite and a minimum requirement for any project leader.

	It might also be argued that there was limited personal project management experience of a considerable proportion of survey participants. However, it should be noted that in view of their job functions all respondents must have been exposed to the performance of more or less successful project leaders. The results of this survey thus represent an external opinion of stakeholders of clinical development projects as well as own experience of executive project leaders.

	A next logical step would be to investigate how frequently current clinical project leaders are being rated as successful/ideal along the characteristics that came out as being of highest importance for project success, including their ability of handling different types of communication.

	Effective communication appears to be the key soft skill of a successful/ideal project leader far ahead of clear goals and a proactive working style. This conclusion mirrors the personal perception of 226 clinical research professionals representing predominantly CRO and pharmaceutical companies who work as project managers/clinical trial managers or are interested in this role. Long-term experience in clinical research and overall knowledge of drug development appear, however, to be less important for a project leader as compared to other knowledge, behavior, and skills. This outcome is in line with the rather scarce literature on the soft skill set of successful clinical project leaders. Required technical skills that are prerequisites for this job function were not subject to this survey.

	It appears to be mandatory that training programs offered to clinical project leaders attach high value to excelling in soft skills with a focus on effective communication and appropriate working style. The obvious aim would be to strengthen clinical development teams and boost the effectiveness of clinical development programs.

* MD, PMP, has worked at PPH plus as Project Leader. He is currently Clinical Research Physician at Boehringer Ingelheim, Biberach an der Riss, Germany, e-mail: 

 MD, FFPM, is Managing Director & COO at PPH plus, Frankfurt am Main, Germany, e-mail: 

	*To whom all correspondence should be addressed.

	J. Koedam and J. Schenk, "Project Leadership: Getting It Right," 

	C. Burgess, "The Changing Role of Project Managers," 

	M. Moyer and M. Dunphy, "Management vs. Leadership – How to Strike the Perfect Balance," 

A Guide to the Project Management Body Of Knowledge (PMBOK® Guide)

-Fourth Edition (PMI, Newtown Square, PA, 2008).

	G. J. Skulmoski and F. Hartman, "Information Systems Project Manager Soft Competencies: A Project-Phase Investigation," 

	PM Tutorial. "Project Management 101: The Project Manager-Administrative Skills," 

, Project Management Institute (PMI) (1994).

	PM Tutorial. "Project Management 101: The Project Manager-Technical Skills," 

	J. Kelso, "No Matter Your Title, Effective Communication is Vital," 

, Project Management Institute (PMI) (1997).

Four New Skills for the Human Side of Project Management

, Proceedings of PMI Global Congress 2003-North America.

Evaluating Communication Effectiveness in a Project Environment

, Proceedings of PMI Global Congress 2003-Europe.

Project Communication: Effective Writing Styles and Cross-Cultural Considerations

Proceedings of PMI Global Congress 2004-North America.

Effective Project Leadership: A Combination of Project Manager Skills and Competencies in Context,

 Proceedings of PMI Research Conference 2006.

	E. Muzio et al., "Soft Skills Quantification (SSQ) for Project Manager Competencies," 

Intercultural Communication in Global Business,

 Proceedings of PMI Global Congress 2008-Asia Pacific.

Senior Management Perceptions of Effective Project Manager Behavior: An Exploration of a Core Set of Behaviors for Superior Project Managers

, Proceedings of PMI Research Conference 2008.

 Proceedings of PMI Research Conference 2000, Paris, France.

	DIA Conference "The Future of Pharmaceutical Project Management," Tutorial on "Leadership: How We Do It and How We Can Do It BETTER" at Weston, Florida (2007).

Feature Article

A survey of clinical research professionals asked: What makes you a successful project leader?

Leading Clinical Projects

There are a number of common adages that float around the clinical trial industry, which are usually based in some form of truth: 

Access to patients is the number one problem in clinical research.

Eighty percent of patients come from 20% of sites, but sponsors keep going back to 100% of sites.

Monitoring hours are one of the highest costs in a clinical trial. 

 Laurie Jassenoff, Vice President, Palm Beach Research Center  

These phrases, while sounding cliché, do highlight some of the most frequent and cost-heavy challenges in clinical research and relate in one way or another to effective clinical trial management. But the questions remain: How do organizations proactively manage the many different moving pieces and parts of a trial? How can sponsors and CROs alike harvest and institutionalize information on how to run trials effectively? How can operational managers see useful information across dozens of trials to keep programs on track and identify potential problems before they happen?  

These are the types of problems a clinical trial management system (CTMS) can address. However, it is not always a smooth and seamless process.  

When web-based EDC and automated randomization systems emerged over a dozen years ago it seemed that some of these new systems might eliminate the need for standalone CTMSs. That has not proven to be the case. The need for CTMS is still important for sponsors, CROs, and sites.  

Many technology systems are touted to include "business intelligence" or digital dashboards and compatibility with other systems. It's also become common to include compatibility and integration with other data management systems as a core capability of eClinical systems, but it's more difficult to implement in ways that are meaningful and beneficial to end users.  

This was the case with Palm Beach Research Center, an investigation site that conducts Phase I-IV clinical programs. Laurie Jassenoff, MBA, Vice President of Palm Beach explains, "Today, to get any kind of information on a clinical research program we have to query a particular database. If we want to look at studies, that's one database. If we want to look at studies with patients, that's a different database. It takes a lot of extra time and effort. When I log into my bank account I can view all my accounts at once. It would be great if as a researcher I could sign on to one integrated database with the same kind of front page to access all the information I need." 

And while many systems can integrate with other systems, providing compliance and industry standards capabilities, there are cost and time considerations to integration that must be accounted for. Because integration can be difficult, many organizations can end up using different data sources during trial conduct and go through the process of merging data at the end. Janssenoff says, "for example, it would be a huge time saver if we can enter our source data and it merges with the eCRF." 

Palm Beach Research Center is rolling out a CTMS in 2013. "Our goal is for the CTMS to become a huge patient database that will be able to show cross references of studies and patients, and patients in studies, in addition to having budget information integrated to show what we are invoicing and what is outstanding." Jassenoff said, "Ideally I'd like to be able to review this integrated data on my iPad anywhere, any time."  

CTMS integrations make a great deal of business sense. The combined data streams provide real-time trial information that may come from ePRO, IVRS, and EDC systems that roll directly into CTMSs and roll up into a real time view of a trial.  

How will CTMS look 10 years from now? That's what vendors and organizations alike are contemplating.  

The likelihood seems strong that cloud-based computing will make it easier to provide meaningful dashboards from data across trials. The resulting information should flow more easily across systems into data warehouses and reporting servers that provide that actionable knowledge to a variety of stakeholders about the way trials are run.  

—Sheila Rocchio, Vice President of PHT Corporation

There are a number of common adages that float around the clinical trial industry, which are usually based in some form of truth.

Clinical Trial Management Systems: Here to Stay?

, (London, UK and Wilmington, NC) a global CRO, announced that 

have been promoted, coinciding with the appointment of 

, PhD, as CEO. Smink, previously Senior Executive VP, Global Clinical Development, has been named Chief Operating Officer. Christmas, formerly Senior Executive VP, Global Resourcing Solutions, has been named Chief Resourcing Officer. Chiltern also announced that 

 have joined the company, bringing experience in clinical research to strengthen the global clinical development services.  

(Malvern, PA) has appointed a new Chief Technology Officer to continue development of the company's technology innovations. 

 will be responsible for managing large-scale technology and service transformation engagements as well as delivering strategic consulting and ongoing technology service delivery to customers.  

• The Patient-Centered Outcomes Research Institute (PCORI)

, MBA, MIM, as Director of Patient Engagement. Sheridan, who served as PCORI's Deputy Director of Patient Engagement since February, will be responsible for the development and execution of PCORI's patient engagement strategy to bring the voices of patients, caregivers, and patient advocates to PCORI's research agenda. 

• CTI Clinical Trial and Consulting Services 

, PhD, RN, has joined as Director, Regulatory and Scientific Affairs, and 

, BS, PA, has joined as Assistant Director, Medical and Scientific Affairs. 

 to its senior staff as Director of Quality Assurance. Most recently the Associate Director of Clinical Quality Assurance for South San Francisco's Janssen Alzheimer Immunotherapy Research & Development, Wong joins ProTrials with more than 15 years of industry experience in quality and regulatory compliance. 

, MBA, CIP, as its Northeast Corporate Business Development Representative, based in Cambridge, MA.  Scott has worked for Quorum Review for seven years, most recently as an Institution Specialist. She brings customer service and clinical research experience to serve Quorum's clients in Northeast region. 

 to the company's Client Services Department. Panzer and Court will contribute their knowledge and experience in managing day-to-day client team activities. 

 (Raleigh, NC) announced the appointment of 

, PhD, as Vice President, Regulatory Strategy, Consulting and Submissions. Ryan aims to provide global leadership to position INC Strategic Advisory Services as a market leader in regulatory consulting and submissions offerings. 

 (Burlington, MA) announced organizational changes within its clinical group. 

 is joining the company as Executive Vice President of Clinical, and will be responsible for leading the company's clinical business segment, which includes early stage, Phase II-IV, and strategic resourcing. 

, (Plymouth Meeting, PA) the developer of the TrialMax Suite of electronic Clinical Outcome Assessment Solutions (eCOA) for the life sciences industry, was named to the 2012 edition of the Deloitte's Technology Fast 500 for its proprietary intellectual technology. The TrialMax Suite of eCOA solutions enables the collection, management, and near real-time visibility of clinical research data reported directly from patients, clinical observers, and investigators. 

 (Princeton, NJ) announced the CEO Roundtable on Cancer accredited the company with the CEO Cancer Gold Standard, recognizing the organization's commitment to the health of its employees and their families. The CEO Cancer Gold Standard is a series of cancer-related recommendations developed by the CEO Roundtable on Cancer, a non-profit organization of cancer-fighting CEOs whose mission is to make continual progress toward the elimination of cancer as a personal disease and public health problem. 

 (Fort Lauderdale, FL) announced it ranked 286th on Deloitte's Technology Fast 500, a ranking of the 500 fastest growing technology, media, telecommunications, life sciences, and clean technology companies in North America. OmniComm grew 265% during this period. 

 (Tempe, AZ) received top honors in this year's Best in Biz Awards, the only independent business awards program judged by members of the press and industry analysts. CRA received the Gold Award for Business Development Department of the Year. 

, Vice President of Business Development, and 

, Director of Business Development, were recognized for their achievements in helping the company grow. 

• Clinical Research Management, Inc. (ClinicalRM) 

(Hinckley, OH) announced it was awarded a US Army Medical Materiel Development Activity (USAMMDA) contract. With this contract, ClinicalRM will provide regulatory support personnel and may also provide equipment, supplies, facilities, transportations, tools, and materials necessary to support USAMMDA's mission. 

(Boston, MA) Board of Governors has adopted 47 revised methodology standards to guide the conduct of patient-centered outcomes research as recommended by PCORI's Methodology Committee. A full narrative report, providing context for the standards, will be revised and published next spring. 

• The Clinical Data Interchange Standards Consortium (CDISC)

 (Austin, TX) used the CDISC International Interchange to formally launch the Coalition for Accelerating Standards and Therapies (CFAST). It also marked the 10th anniversary of these CDISC Interchanges. 

, (Boston, MA) a CRO focused on maximizing the precision and accuracy of independent assessments in clinical trials, has in collaboration with Sheela Agarwal, Massachusetts General Hospital, Division of Abdominal and Interventional Radiology, to publish a review article entitled "US FDA Draft Guidance Standard for Clinical Trial Imaging Endpoints: More Than Just Imaging?" in the December Issue of 

 (Austin, TX) announced the launch of the inaugural CDISC Asia-Pacific Interchange to be held February 18-22, 2013, in Singapore. Singapore was chosen for its central location in this region, the epicenter of some of the most booming economies in the world. The core message of the CDISC 2013 Asia-Pacific Interchange is "Streamlining Global Research through Standards," and representatives from local Asia-Pacific ministries of health, pharmaceutical companies, clinical research organizations, technology service firms, and non-governmental organizations will be in attendance. 

(Rochester, NY) announced that it has relocated its laboratory facilities in York, England. The move to a larger facility is in response to growing client demand for ACM Global's clinical trials testing services throughout Europe, including Western and Eastern Europe, as well as South Africa and the Middle East.  

 (Durham, NC) has introduced a new study simulation and forecasting service that will enable clinical trial sites to better plan and control supplies for their patients. When integrated with Cenduit's interactive response technology (IRT) services, the new service aims to give sponsors confidence in their clinical supply chain. 

(Westborough, MA) announced the release of I-Accountability, a drug accountability system that aims to efficiently track and control drug inventory and randomization. 

Business News

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

Business and News Update January 2013

As site costs continue to increase in the more traditional areas for clinical research, a growing number of CRO's and sponsors are using sites in areas such as Latin America, Asia, and Eastern Europe according to GrantPlan. The demand for less expensive markets have increased as sponsors and CRO's reach toward less expensive regions in which to conduct clinical trials. Lower costs will never be the decisive consideration in selecting a site, however, substantial cost differences are becoming more important in the decision making process. 

TTC, now a part of IMS, continues to provide annual current global data on the relative costs of clinical grants around the world using the GrantPlan database. The aggregate GrantPlan subscribers conduct nearly 80% of all commercial clinical trials around the world, with each sponsor company and CRO contributing the current costs of each clinical trial.  

 Mean cost per visit in Phase II-III clinical trials.

This year, the data shows the United States and the United Kingdom continues to be the most expensive countries for clinical grants. With low single digit growth in the established geographies, grant costs seem to have stabilized. Despite the increased demand, the newer geographies have experienced a slight decrease in the costs per visit of approximately 6% in Asia and a minimal increase in Latin America.  

—TTC (for more information, please contact 

Revisiting Clinical Grant Expenditures

Intense pressure to streamline the drug development process by making clinical research more efficient is prompting a wave of joint initiatives among pharmaceutical companies, government agencies, and academic medical centers. Sponsors are identifying precompetitive areas that can benefit from combining data and resources, while the Food and Drug Administration is encouraging public-private partnerships to develop data standards, biomarkers, and eSubmissison methods.  

Support comes from the National Institutes of Health's National Center for Applied Translational Sciences (NCATS), which is collaborating with eight pharma companies on drug repurposing programs and building teams to tackle a range of projects involving rare and neglected diseases. At a November Brookings Institution conference on "New Policy Directions for Biomedical Innovation," NCATS Director Christopher Austin also cited efforts to establish interoperable databases, common IRBs, and specialized research centers to support a shift away from the vertically integrated research model, which "does not work anymore." A squeeze on resources at federal agencies and industry, moreover, is prompting patient and disease groups to play a larger role in funding collaborative research efforts, while healthcare systems are looking to utilize extensive patient data banks to support research that will improve patient care.  

In September, 10 big pharma companies unveiled the TransCelerate BioPharma collaboration to speed up new drug R&D by seeking standardization in data collection, study site qualification and monitoring, investigator training, and procurement of marketed drugs for use in comparative trials (see ACT "View From Washington," November 2012). TransCelerate recognizes it will benefit from collaborative efforts already underway by the Clinical Data Interchange Standards Consortium (CDISC); the Critical Path Institute (C-Path); the Clinical Trials Transformation Initiative, headed by Duke University and FDA; the Innovative Medicines Initiative (IMI) in the European Union; and others.  

One recent offshoot is the global Investigator Databank, designed to provide information on the training, skills, and experience of investigators and clinical sites so every sponsor doesn't have to start from scratch in forming study networks for new trials. Janssen R&D clinical trial innovation head Andreas Koester announced in November that Merck and Eli Lilly were joining this effort to reduce redundant site assessments and repeat investigator training in good clinical practices. Other biopharma companies and contract research organizations may join the project with an eye to lowering the administrative burden on investigators sufficiently to expand the pool of trained clinical researchers in the United States and overseas. 

Separately, several leading pharma companies agreed in October to share clinical trial data from cancer studies in a new database dubbed Project Data Sphere. Launched by the CEO Roundtable on Cancer Life Sciences Consortium headed by Sanofi CEO Chris Viehbacher, participants will provide historic study data to facilitate comparisons of different treatment regimens. 

The Cancer Roundtable and other research streamlining initiatives stand to benefit from data standards for collecting and transmitting study data. To this end, CDISC, C-Path, and FDA officially announced the Coalition for Accelerating Standards and Therapies (CFAST) at the October CDISC International Exchange meeting. Added support comes from IMI, Japan's Translational Research Informatics Institute, the Bill and Melinda Gates Foundation and, other research and disease groups.  

CFAST's stated goal is to map standards for 57 therapeutic categories in five years. That ambitious schedule will be hard to meet, as debate continues over data transport standards for submitting files to FDA, audit trails, data integration, and the need to reduce data file size, among other issues. In the past 10 years, CDISC has developed and posted only three therapeutic area (TA) data standards, for Alzheimer's disease, pain, and tuberculosis. Additional standards are under review for cardiovascular disease, Parkinson's, polycystic kidney disease, and virology; diabetes and asthma top the CFAST priority list.  

Yet, the FDA Safety and Innovation Act (FDASIA) provides a strong impetus for moving forward. The legislation calls for the development of standardized clinical data terminology through an open process, and for FDA to publish guidance to implement these standards. In addition to accelerating clinical research, TA standards will help FDA provide more consistent reviews, more quantitative approaches to benefit-risk assessment, and more timely post-market safety analysis. At the CDISC exchange meeting, Janet Woodcock, Director of the Center for Drug Evaluation and Research, noted that FDA receives nearly 1,300 datasets a week and needs standards to accomplish a much-needed shift to eSubmissions by 2017 to meet the FDASIA goal.  

Intense pressure to streamline the drug development process by making clinical research more efficient is prompting a wave of joint initiatives among pharmaceutical companies, government agencies, and academic medical centers.

Collaboration Key to Modernizing Clinical Trials

The European Medicines Agency is at battle stations as the new year unfolds—and don't be surprised if you get a slightly grumpy response from them. It said at the end of 2012 that it expected about 100 applications for human medicines during 2013, including more than 50 applications for new medicines. This does not include designated orphan medicines, of which it is expecting about 20 new applications. Alongside, some 20 generic applications are expected. The figures are broadly similar to 2012, and the agency's predictions are in some respects a measure of optimism against a rather somber background. 

At the most local level, the agency itself is strapped for cash and resources, while its responsibilities are increasing. It foresees "a difficult economic environment." It will be operating on a budget of €231.6 million ($307 million), slightly up from 2012, assuming fee revenue from services provided to companies reaches the planned level of €179.8 million ($238 million). At the same time, as a faithful servant of the European Union, it will have to put new legislation into effect.  

The EU pharmacovigilance rules in force since mid-2012 are the most evident example. In 2013 the agency has to collect key information on medicines; prepare guidance for patient reporting; ensure better analysis and understanding of data and information; take regulatory action, particularly coordination of pharmacovigilance inspections; and widen its communications. But, as the agency points out, the fees that companies will have to pay for pharmacovigilance services are not expected before 2015. And on top of the pharmacovigilance rules, new EU legislation to prevent falsified medicines getting into the legal supply chain also comes into force in 2013. This will require the agency to become involved in developing an EU database of certificates of good manufacturing practice and good distribution practice from the 27 member states. 

The strains are compounded by the obligation to conduct a constantly growing range of activities which generate no fee revenue (such as greater support to the scientific committees, monitoring conflicts of interests more sharply, or early-stage consultation and advice to applicants), and which have to be funded through cross-subsidisation from fee-generating activities. An internal program aimed at increasing efficiency of operations will continue, including bringing in a new information and communication technology strategy. 

And above all, the agency is still going to be under close scrutiny from the European Parliament on many of the issues that plagued it in the preceding two years—not just the high-profile issues of avoiding conflicts of interest, but also financial and human resources management, and transparency. Guido Rasi, the Executive Director, has made big changes since he took over, but he now has to make a success of one of his flagship exercises in transparency—widening access to clinical trial data. Following a workshop on the subject in late 2012, the plan is to start a consultation process at the beginning of 2013, with a view to publishing a policy in early 2014 on the release of data from clinical trials. 

There are other clouds on the agency's horizon. Not only the European Parliament has been examining the agency's operations. The Court of Auditors—the European Union's main watchdog—released a critical report on the agency's management practices in October 2012. The criticism was partly out of date because the report itself was nearly a year old when it was published, but the auditors are not going to let the agency out of their sights now that they have entered the fray.  

Even more significantly, the European Commission has committed itself to a root-and-branch review of all its specialized agencies—there are more than 30 of them, dealing with subjects as diverse as trademarks and occupational health and safety, but the medicines agency is one of the most prominent. There is a growing feeling within the commission that these agencies are getting out of control—and control is one of the commission's principal roles within the European Union. So nothing can be excluded as the commission tries to bring new coherence to a plethora of these subsidiary operations set up more or less at random over the last 20 years: the result could be changes in their constitution, their mission, their scope of operations, their funding, or their supervision. The only thing it is almost certainly not going to result in is greater autonomy and independence.  

So treat the agency gently if you want it to treat you gently over the coming months. 

One subject that the agency's 2013 planning does not make any specific mention of is the ongoing attempt to update the EU's rules on clinical trials. In fact mild disappointment has on occasions been perceptible within the agency at the limited degree of engagement that it has been offered by the European Commission in this exercise: it was not formally consulted by the commission during the preparation of the draft regulation that appeared in July.  

The discussion of this proposal is going ahead at several levels in Europe as 2012 ends and 2013 begins—and is being described by people close to it as "a very lively and hard debate." This column has already reported on some of the difficulties identified by ethics committees in the commission's proposal. Recent discussions have not eased their concerns, and many of them remain without any idea as to how they could handle the requirements, especially the tight new timelines envisioned, and the links that will have to be built by each member state between ethics committee assessment and regulatory review so as to obtain a single national decision.  

The feeling is growing that a mention of "ethics committee" will have to be reinstated somewhere in the legal text (the term does not appear even once in the current draft of the regulation), both to match state-of-the-art regulation of clinical research, and also to provide reassurance that ethics committees will have a mandate to negotiate with their national health authorities about their role. For the timelines, on which ethics committee members are particularly concerned because they fear that tighter deadlines could jeopardize the quality of the existing review mechanisms, some leading European figures, such as Ingrid Klingmann of EFGCP, believe that compromise is possible, and some ways can be found to achieve shorter timelines without reducing the quality of reviews. She believes it will be necessary to give a lot of support to ethics committees in some countries, and that greater precision is needed in subjects like informed consent in vulnerable populations, definitions of concepts such as "low-intervention-trial," and arrangements for safety reporting or indemnity. 

But many supporters of improved regulation—and there are many of them across Europe—are dismayed at what looks like almost total inaction by national authorities in trying to find ways of rising to the challenge posed by the draft regulation of developing a reliable and effective system for evaluating clinical trial authorization applications. Some observers put the member states' inactivity down to pique—because many suggestions from the national authorities in Europe were largely ignored by the commission as the draft was finalized. So far there is little evidence of national authorities coming together in any sort of formal (or even informal) task force to look at how they could fill in the blanks that the commission proposal leaves open for them. 

Within the European Parliament, the discussion is still in a preparatory stage. The member who has chief responsibility for guiding the debates through the tortuous legislative procedure is a British socialist, Glenis Wilmot, who is leader of the European Parliamentary Labor Party and spokesperson for UK socialist MEPs on health. "I'm delighted to be steering this crucial piece of legislation through the European Parliament, and to be negotiating the final text with EU governments," she said in a statement when she was appointed to the task.  

"There couldn't be a better time to be changing these rules. If we get them right they could create many skilled jobs in the United Kingdom and Europe, as well as leading to new life-saving treatments and drugs." She said she was aware that Europe's traditional dominance in medical research was at stake, and that the decline in clinical trials in the European Union in the last few years is "partly due to failures in the existing rules" as well as to competition from emerging markets.  

"Simplifying the rules will encourage more European trials, not just by pharmaceutical companies but also by medical research charities and academic institutions," she said. Wilmott says the core issue for her will be trying to cut the administrative burden of carrying out a trial in several countries—"one of the most pressing problems with the current rules," she said. However, as this edition of 

 went to press in late December, she had still not produced a draft report on the proposal, and formal discussions will therefore not start until January. 

 is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium. 

View from Brussels

The EMA's predictions are a measure of optimism against a rather somber background.

New Year Challenges and Promises in Europe

Human nature being what it is, in any environment there is always the possibility that someone has done something wrong. In the context of clinical research such wrongdoing might be some aspect of research misconduct such as fabrication of data, falsification of results, plagiarism, or piracy. If the misconduct is carried out with the intent to deceive, that's fraud. 

I've been fraud-busting for over two decades now, and although the most obvious cases have almost disappeared, research fraud still exists. Breaches of good clinical practice occur all the time, but so long as they are not intentional, only sloppy, they will most likely be picked up by the vigilant monitor or the astute auditor. Unfortunately, where the deception really is intentional, the fraudster will go out of his way (in my experience always "his" not "her") to cover his tracks—we do not know what we do not know. So although I'm confident that research fraud is not rife, it still exists and those of us with the interests of research integrity at heart must do all we can to minimize it and not become complacent. 

People often accuse me of using platitudes, but I stick to my firm conviction that "once a fraudster, always a fraudster," because time and again I come across multiple instances of fraud committed by the same person. So it makes sense never, ever, to use again as a researcher anyone who has demonstrated any degree of research misconduct. However, sponsors sometimes wish for research to be led by a known specialist in that particular field, and the temptation to acquiesce to such a wish if the potential investigator is known to have committed research misconduct must be resisted. 

Everyone who is involved in clinical research should have a set of standard operating procedures in place for the handling of suspected research misconduct. Furthermore, they should be familiar with how such a procedure operates and should ensure that it remains up-to-date. Because such misconduct is not rife, the need to use this procedure may not often arise, but when it does, it should be used without delay. In my extensive experience, academic departments and universities are singularly ill-prepared or are unwilling to invoke the procedure they have in place and are much more likely to sweep any irregularity under the carpet. But it is incredibly irresponsible and potentially dangerous to do that, as the rogue investigator who fabricates or fantasizes will be liable to go on repeating his misdemeanours if he is not stopped. Furthermore, whistle-blowers who have identified where research is being corrupted are, even now, more likely to be told to shut up than to be commended for exposing the shortcomings of the suspect investigator. 

Integrity must therefore be maintained at all costs. However, I'm well aware that honesty in the conduct of research can be difficult to maintain, especially when time is running out, some of the figures are missing, the analysis proves nothing at all, and there is no more money for the project. But reporting that the outcome of the research is inconclusive or that the results are negative is important in itself as well as being honest. Such information can well save time and money if it is reported that certain processes don't work, so that that particular dead-end can be avoided in the future. 

I hope the readers will agree with me that the utmost vigour is needed to apply a policy that minimizes the incidence of research misconduct; because it is in the ultimate interest of all involved, and especially patients, that this is done and that the integrity of future research can be safeguarded. 

 Retired Pharmaceutical Physician  Lead Advisor on Integrity Fraud  and Misconduct to the Health Research Authority  E-mail: 

A Closing Thought

Standard operating procedures need to be in place for the handling of suspected research misconduct.

Research Integrity

The European Medicines Agency has announced progress with its plans to increase access to clinical trial data and transparency, and is making this topic an urgent priority during 2013. 

During a special workshop held in London on November 22, 2012, the EMA identified five key areas of concern: protecting patient confidentiality, clinical trial data formats, rules of engagement, good analysis practice, and legal aspects. It is forming advisory groups that will start work on these topics in early 2013. 

Nominations for membership of these groups were due to close on December 21, 2012. On December 18, an EMA spokeswoman told 

 she was not able to confirm the exact number of applications, but she noted that there were over 60 responses in the first two days. "We are very pleased with the outcome and the deadline will not be extended," she added. 

The agency has promised to inform interested parties about the final membership of the groups in early January 2013. The agency will only accept one member from the same organization in each advisory group. 

Both Executive Director, Guido Rasi, PhD, and Senior Medical Officer, Hans-Georg Eichler, MD, have taken a personal interest and been closely involved in the process. They support the concept of proactively publishing clinical trial data and enabling access to full datasets by interested parties. 

According to an EMA statement, "Each group will meet one to three times between January and April 2013, with meetings taking place both face-to-face and via teleconference. Participants will also need to provide input via e-mail during the drafting of documents. The policy on proactive publication of clinical trial data is expected to come into force on January 1, 2014." 

The groups will address the following questions over the coming weeks: 			

How can EMA ensure that patients cannot be retroactively identified when clinical trial data are released, and that applicable legislation, standards, and rules regarding personal data protection will be respected? 

How can EMA ensure through its policy that clinical trial data can be shared, in the interests of public health, in a clear and understandable format that enables appropriate analyses and a swift implementation without undue burden to stakeholders? 

 Are there rules or conditions that should be in place before an external stakeholder can download clinical trial data (e.g., formal acceptance of the need to respect personal data rules, uploading of analysis plans. etc.)? 

Are there good analysis practice guidelines that the EMA could ask external requestors of data to consider or be aware of, and that the agency can apply when confronted with additional analyses from external parties? 

Are there exceptional circumstances under which data can be claimed to be commercially confidential? 

A number of practical and policy issues need to be addressed before complex datasets can be made available, according to EMA. The main goal of the London workshop was to elicit the views, interests, and concerns from a broad range of institutions, groups, and individuals to help the agency define the modalities of proactive access to clinical trial data. 

"We must ensure that all information from all trials, past and present, are available to all doctors, patients, and academics. This is the only way to make informed decisions," said Ben Goldacre, MD, a UK-based commentator and author who covers clinical research.  

Another workshop participant, journal editor Virginia Barbour, said that any move toward better transparency must be a global initiative. She admitted there are many practical issues to sort out, but they are not insurmountable if everybody works together.  

"The days of secrecy must end," Peter Gøtzsche, a Danish medical researcher who is Director of the Nordic Cochrane Center at Rigshospitalet in Copenhagen, told attendees at the meeting.  

The European Federation of Pharmaceutical Industries and Associations (EFPIA) is committed to working with EMA and other stakeholders to develop an approach to foster transparency that is appropriate and balanced, according to Susan Forda, PhD, Chair of EFPIA's Scientific, Technical, Regulatory Policy Committee. 

According to François Houÿez, representative of EURORDIS (Rare Diseases Europe, a non-governmental patient-driven alliance of rare disease patient organizations), gaining access to clinical trial data would benefit many people. "It would be useful to those people looking for new products in different indications, especially if we had access to the data for products that did not make it to market," he told delegates at the London meeting. 

The European Medicines Agency has announced progress with its plans to increase access to clinical trial data and transparency.

EMA Forges Ahead with Data Access Initiative

Outsourcing has played an important role in drug development for more than 30 years. But arguably, that role has been largely reactive to sponsor needs and direction. New outsourcing relationships are a potential game-changer: leading CROs are now positioned to play an unprecedented new role in proactively and aggressively transforming clinical research. 

Here's how: strategic and integrated partnerships are facilitating the rapid transfer of operating and resource risk from pharmaceutical companies to CROs. To successfully manage these highly valued relationships, leading contract service providers are taking on substantially more fixed costs, assuming more autonomy and accountability, and investing in the adoption of innovative practices and solutions at levels that far surpass those typically made by their counterpart, risk-averse sponsor companies.  

Nearly all large sponsor companies—major and many mid-sized pharmaceutical and biotechnology companies—have actively embraced the use of integrated relationships where entire functions or portions of a portfolio are managed more autonomously by select preferred providers under long-term alliance arrangements. Sponsors hope to not only access dedicated global capacity, talent, and experience more efficiently, but also to secure cost savings through reduced start-up and guaranteed portfolio activity.  

The largest CROs are uniquely positioned to provide the breadth and depth of capacity that sponsor portfolios require. These CROs have been the primary beneficiaries of integrated and strategic partnerships. A recent study conducted by CenterWatch found that for leading CRO companies, the majority of their revenue comes from strategic, integrated relationships. Among the top 10 largest CROs, 71% of their reported revenue comes from functional service and integrated alliances, and 29% from transactional relationships. In contrast, the majority (60%) of revenue for niche and mid-size CROs comes from transactional service relationships. Smaller pharmaceutical and biotechnology companies continue to primarily use transactional relationship outsourcing —often under preferred arrangements—to augment capacity for a specific project-related task. 

Greater autonomy in managing large and highly valued integrated partnerships is but one aspect of operating and resource risk transferred to CROs. Customization is also driving up risk since no two partnerships are identical. One sponsor's integrated alliance is not the same as another. Every sponsor wants to establish relationships that uniquely suit their culture, operating style, strategy, systems, practices, and management models. Each and every sponsor wants to match its internal teams with the best team that the contract service partner can offer. Customization cannot be scaled. It demands greater CRO infrastructure and management, erodes the CRO's ability to operate efficiently, and squeezes CRO company profitability. 

An overwhelming majority of CRO professionals (80%) expect sponsor-use of integrated alliances to continue to significantly increase during the next three-to-five years according to that same CenterWatch study noted earlier. The capital markets affirm this optimism. GBI Research, for example, forecasts a 12% to 15% annual growth rate in the contract clinical services market through 2020.  

Market leading CROs covet their integrated, strategic relationships. These relationships have high revenue potential and offer continuity and access to the largest and most active pharmaceutical and biotechnology companies. Next-tier CROs have also looked to get in on the game by scaling capacity and capabilities through mergers and acquisitions.  

As integrated alliances assume more risk, novel strategies and practice must follow.

Applied Clinical Trials-01-01-2013