The complexity of a protocol is the measure of effort required to conduct the study and is a key component for its success from a scientific, execution, and financial planning perspective. Complexity of study protocols is primarily determined by the number/frequency and/or complexity of unique individual procedures required in the study. A more complex protocol requires bigger budgets to support the protocol procedures from a regulatory, scientific, and operational standpoint. It may also warrant a more specific and stringent selection of patients in the study and consequently impact patient recruitment—subject screening and enrollment at sites, besides increasing the associated site burden.  

This month's Insights graph provides a comparative evaluation of protocol complexity against the ratio of enrolled to screened patients. This data is derived from studies in the Medidata Insights metrics warehouse between 2007 and 2011. As is evident from the graph—and was reported previously in our blog in August—the complexity of protocols has increased steadily in the past five years. Interestingly, this increase in protocol complexity is accompanied by a downward trend in the ratio of enrolled-to-screened patients. While it is important to understand that these two data trends are coming from two distinct components of the metrics warehouse, where there is not a one-to-one direct relationship or correlation between protocol complexity in a study and enrollment rates in that same study, at a macro level, this analysis highlights that increasing complexity of protocols correlates with either higher patient screening or lower patient enrollment, or both. In other words, when viewed at an aggregate level across the industry, increasing protocol complexity negatively impacts patient recruitment.  

As we've discussed before, it is fair to assume that increased protocol complexity drives an increase in eCRF complexity and design timelines, monitoring costs and burden on both sites and patients—overall increasing the costs and timelines associated with clinical trials. Given that 15% to 30% of data collected in a clinical trial is never used in a new drug application, it is a bigger concern if the added complexity without corresponding increases in value, is negatively impacting patient recruitment. And of course, since patient recruitment continues to be a major concern for the industry, any factor that impacts it negatively should be carefully analyzed. Additionally, recent research from Tufts CSDD shows that up to a quarter of clinical procedures as defined in a protocol may be unnecessary, further driving up complexity and costs. It is therefore important that high quality protocols be designed with careful consideration to complexity, ensuring well-defined screening criteria optimizing subject enrollment and ultimately, patient safety. 

What is your view on the relationship between protocol complexity and patient recruitment? As always, Medidata is interested to hear your take on this result. Please stay tuned as the company delves further into Insights metrics like these in 2013. 

Articles

Data Anlaysis

Protocol Complexity Versus Patient Enrollment

Issue PDF

SURVEY : Salary and Career Development Survey   Also in this issue : EU Employment, Business and People Update, Investigator Training

Applied Clinical Trials Digital Edition - December 2012

ICH GCP, the backbone of clinical research in the ICH regions has been in place for more than 15 years. Repeated training on this standard has been conducted as we have no other way of recognizing whether the investigators who work on our studies are suitably qualified. Despite all this training the same findings keep occurring. The pharma industry needs to re-think its approach as our previous efforts have clearly not been effective. 

Development of investigator training on aspects of GCP by an independent body that regulates the courses and provides tangible evidence of achievement as defined by the accrediting body is the way forward. We need to ensure that investigator attendance is not just passive, and that learning outcomes are clearly defined and are fit for purpose. Investigator training should not be a "one-off" session at the start of clinical trial, but a continual assessment with repeated re-certification at clearly defined time points. 

When we think about the requirements of the "independent body" it is important that they have a suitable infrastructure with trainers who have the knowledge and expertise to deliver education. The GCP course should cover the required elements as "bite-sized learning" or a modular approach, so topics can be studied at convenient times. The nuances of GCP using real-life experience along with conducting testing at the beginning and at the end of each module will make this more applicable to investigators in their daily activities and will help to focus the investigator on the training being delivered.  

Training will need to fulfill set requirements and be recognized by the pharma industry. Undoubtedly this is a cultural shift in the way the industry currently works, but there are several companies that are now starting to work together in this direction. 

If this type of training is established we must ensure that this is not just to benefit the pharma industry. Training such as this will have mutual benefits to the investigator and their site staff and also increase public confidence in the way clinical research is conducted. When clinical research professionals attend training that provides them with a recognized accreditation this will also support the development of their career. Accreditations will need to be recognized by their employers and be transferable.  

The pharma industry has been reticent about sharing best practices in the past and has been reluctant to work together on such projects. The involvement of "independent bodies" acting as an intermediary could be the way forward, the issue may be the fact that there are several of these organizations currently starting to be involved in this process which could be counterproductive. It may take a government or national body or a more global "independent" organization to finally make this work. 

The spirit of harmonization has never been greater, so now is the time to work together to standardize investigator GCP training and establish mutually recognized certified courses that can deliver effective understanding of the requirements, enhancing the quality of data and patient safety. Industry support is vital in helping define and establish such training. It is to our advantage that we support this initiative as this has significant time and cost implications—the previous way we have worked has not been successful. Now is the time for change and we are the ones that can make it happen. 

Vice President, Global Quality Assurance, Premier Research Group E-mail: 

A Closing Thought

Investigator training should not be a "one-off" session at the start of clinical trial.

Oh No Not Again...

Awell documented 2008 study titled "Sensible Approaches for Reducing Clinical Trial Costs," 

http://ctj.sagepub.com/content/5/1/75.abstract

 found that investigator payments account for a staggering 48% of total trial costs. So it goes without saying that sponsors and CROs can't afford to get the investigator payment level wrong. For sponsors and CROs, not paying market-rate investigator fees impacts both the financial health of the organization and the ability to recruit high-performing and experienced sites. Pay too much and your R&D budget evaporates. Pay too little and it will be difficult to recruit experienced sites. 

But planners need to know when to offer more and when to offer less. Industry Standard Research has recently published a study that identifies the factors that drive investigator fees higher and lower and benchmarked these fees across 11 therapy areas.  

Intuitively it makes sense that study length and complexity would both influence investigator fees. ISR's study quantified just how much. Investigators indicated that both study length and complexity have a dramatic impact on the amount of the investigator fees. For long and/or complex studies, investigator fees can run 50% to 60% higher than for more standard studies. 

Knowing what levers push and pull investigator fees—and by how much—will help optimize the use of budgets industry wide and maybe even improve recruitment rates along the way. 

Optimizing Investigator Fees

Act cover

Albert Einstein College of Medicine, Clinical Research Training Program

American College of Clinical Pharmacology

Association of Clinical Research Professionals (ACRP)

Sponsor/CRO

Organizations offering courses and classes designed to broaden your clinical trials knowledge base.

Training and Education

, PhD, will transition from her role as President to that of Patient Recruitment Consultant to the company she founded 20 years ago.  

,(St. Louis, MO) a global provider of digital medical imaging technologies and centralized diagnostic services, has named 

, MD, its chief medical officer for Biomedical's North American operations.  In his role, Pierro and his team will advise clients on their clinical trial protocols, supporting studies conducted in the fields of cardiology, oncology, imaging, and pulmonology. 

, (London, UK) a global contract research organization, announced that 

, (Research Triangle Park, NC) an independent institutional review board, announced the promotion of 

 to Vice President, Quality Management. In addition to her promotion, Higgins has been appointed as CGIRB's Institutional Official. 

, (Dublin, Ireland) a global provider of outsourced development services to pharmaceutical, biotechnology, and medical device industries, announced leadership appointments to its Asia Pacific and Latin American teams. 

 has been appointed Vice President, Asia Pacific, and 

, PhD, has been appointed Vice President, Latin America. 

, (Houston, TX) certification and accreditation agency for imaging quality, announced two new additions. 

, MD, has joined the team as Chief Quality Officer. Siegel will help oversee and promote the integrity of all quality-based programs and research initiatives for RadSite. 

, MD, a board certified radiologist, has also joined the team as Director of Accreditation. Reiner will help ensure RadSite's quality-benchmarking program conforms to current best practice standards. 

, (London, UK) announced a succession of Chief Executive Officer, with 

, (Princeton, NJ) inVentiv Health's clinical segment, announced that 

, MSc, MBA, has joined the company as the Director of Immunochemistry Operations at the Princeton bioanalytical laboratory. 

, PhD, has partnered with the company as a Senior Research Advisor bringing with him a background in biotherapeutic drug research in both traditional pharmaceutical and the CRO industries. 

, (Deerfield, IL) provider of clinical research solutions, announced additions to its leadership team: 

, RN, has been hired as Executive Vice President, Strategic Resourcing; and 

, PhD, has been hired as Executive Director, Clinical Pharmacology and Nonclinical Development. 

, (Spring House, PA) a clinical research organization, brought 

, RpH, onboard as Senior Director, Safety Services. 

 as Vice President of Quality Assurance to support the development of pioneering cloud-based analytics tools. 

• CTI Clinical Trial and Consulting Services 

(Cincinnati, OH) announced the following new hires: 

, MD, has joined CTI Latin America as Manager, Business Development; 

has joined as Clinical Project Manager Europe in Belgium; 

 has joined as Clinical Trial Assistant in Germany; 

 has joined Clinical Research Associate in Germany; 

, PhD, has joined as Clinical Project Manager Europe in France; 

 has joined Clinical Project Manager in United Kingdom. CTI also promoted 

 (Boston, MA and Geneva, Switzerland) announced 

, PhD, has joined as Senior Scientific Advisor in PHT Consulting Services. 

, Director of Data Management, has been named to the Board of Trustees for the Society for Clinical Data Management. 

, human resources and business administration executive, has been named Executive Vice President of Human Resources. 

, (Tempe, AZ) announced that it has acquired Radiant Research, Inc. CRA Holdings also owns Clinical Research Advantage (CRA), another major player in the SMO market. By combining these two entities under the same investment portfolio, the organizations collectively have 57 sites with more than 550 research professionals and a plan for growth. 

, (Austin, TX) announced the addition of ReproSource Fertility Diagnostics of Boston to its network of affiliate laboratories, which provides specialized testing services to clinical trial sponsors and clinical research organizations.  

• Clinical Research Management (ClinicalRM)

, (Hinckley, OH) a full-service CRO providing services for basic and applied research, clinical trials, and regulatory support, announced it will support prime Ke`aki Technologies, LLC with its award of CIO-SP3 contacts for both Small Business and Small Disadvantaged Business categories.  

, (Newton, PA) a global provider of clinical trial management solutions, today announced that TauRx Therapeutics has signed agreements with BioClinica to use Trident IWR/IVR and Imaging Core Lab (ICL) solutions to support its upcoming Phase III clinical trials. 

 RN, BSN, CCRC, has been named as a finalist in the Female Executives of the Year category in the 9th annual Stevie Awards for Women in Business. The awards honor women executives, entrepreneurs, and the companies they run­—worldwide. 

rdale, FL) announced that its TrialMaster Study Data Tabulation Model Export Utility won the Bronze medal at the 2012 Society for Clinical Data Management's 2012 Data Driven Innovation Award Ceremony.  

(Philadelphia, PA) announced it has been named the Life Sciences Company of the Year by the Pittsburgh Technology Council's Tech 50 Awards Program. ERT received the award based on the successes and innovations demonstrated by invivodata, Inc., which was acquired by ERT in July 2012. 

, (Cambridgeshire, UK) provider of early stage and specialist drug development services, has been presented with three awards at the East Cambridgeshire Business Awards. Quotient won awards in both categories they were finalists for; 

 PhD, Associate Director of Business Development won Business Person of the Year, and the company won Employer of the Year. The Awards also saw Quotient receive the Business of the Year award for the second consecutive year. 

 (Chicago, IL) has been recognized by the 

 as one of the Top Workplaces to work in the Chicago metropolitan area for the third consecutive year. Advanced is the only staffing organization to make the Top Workplaces list. 

 (Research Triangle Park, NC) has been recognized as one of the World's Best Multinational Workplaces by the Great Place to Work Institute, finishing 23rd on the list. The ranking is the world's largest annual study of workplace excellence and identifies the top-25 best multinationals in terms of workplace culture. This is Quintiles' second appearance on the list. 

, (Rochester, NY) has expanded its clinical trials services with the introduction of Drug-Induced Organ Toxicity (DIOT) Monitoring. The DIOT Monitoring program provides trending reports for any conventional biomarkers tested, which is tailored to client requirements. 

, (Fort Lauderdale, FL) announced its inclusion in Software Magazine's "Software 500" ranking of the world's largest software companies in 2012. The annual "Software 500" is a revenue-based ranking of the world's largest software and services suppliers and includes revenue from software licenses, maintenance and support, training, and software-related services and consulting.  

, (Seattle, WA) launched its new service, Scientific Operations Support (SciOps), to offer functional outsourcing services to the pharmaceutical research industry. 

, (Stamford, CT) a provider of software solutions to the life science industry, announced the availability of Total Clinical 3.0, offering additional enhancements to its integrated eClinical platform. 

, (Boston, MA) an imaging CRO focused on maximizing the precision and accuracy of independent assessments in clinical trials, announced new locations in Brazil, Dubai, Poland, Spain, and Singapore. 

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

Business and News Update December 2012

Many industries have training standards such as the automotive sector, the renewable energy industry, and specialist areas such as forklift truck driving. In the field of clinical research, guidelines and regulations such as the ICH Harmonized Tripartite Guideline—Guideline for Good Clinical Practice E6(R1) make very general references to training. "Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s)" (ICH GCP principle 2.8). However there is currently no set of standards for how individuals acquire the ability to perform satisfactorily and demonstrate the required levels of competence.  

 The guidelines were designed to share best training practices for anyone involved in the training and development of clinical research professionals. (Source: Getty Images)			

In response, the International Academy of Clinical Research (IAoCR) set up a taskforce to produce GXP training guidelines. The aim of these guidelines is to share best training practices for anyone involved in the training and development of clinical research professionals. The guidelines are designed for use in any organization no matter what size, both in the non-commercial and commercial sectors.  

The guidelines cover the key steps in developing competent individuals, starting with creating a competency framework, through to the assessment of learning and its documentation. The overriding theme of the guidelines is how to use various learning interventions to achieve learner competence. Having competent individuals is vital in clinical research for protecting the rights and well-being of patients and securing verifiable and accurate data. A further benefit is that new treatments for patients can be developed without unnecessary delays or costs due to errors and rework because of incompetence. 

By using the guidelines, organizations can demonstrate a real investment in their people, which leads to other advantages such as increased staff retention and a sound basis for promotions and succession planning. 

The taskforce that created the guidelines was made up of five clinical research professionals from various backgrounds and organizations, and represented Europe, the Americas, and the Indian sub-continent. After some additional input from the IAoCR, the first draft of the guidelines was circulated for consultation to approximately 40 organizations worldwide involved in clinical research and included universities and not-for-profit professional bodies. Following refinement from this initial consultation, a second round of opinion was sought from over 200 individuals working in all sectors of the international clinical research community. The guidelines were finalized and released in mid-November. 

The content of the guidelines covers how to: 					

Design and deliver learning interventions

Assess the effectiveness of the interventions

In addition, there is a set of appendices containing examples, templates, and a reading list for those who want a more in-depth coverage of any of the topics. 

Initial reaction has been very positive. The hope is to see universal take-up of the guidelines in developing competent individuals for the benefit of clinical research worldwide. 

Martin Robinson, PhD, Principal Director, International Academy of Clinical Research Ltd

News

There is currently no set of standards for how individuals acquire the ability to perform satisfactorily and demonstrate the required levels of competence.

The GXP Training Guidelines: Raising Standards Through Competence-Based Training

As commonly defined, Good Clinical Practice (GCP) is an international ethical and scientific quality standard for the design and conduct of clinical trials involving humans. The primary objectives of GCP are to protect the safety, rights, and welfare of subjects, and to ensure the credibility of trial data and resulting reports. The need for ethical standards in clinical practice came about in response to instances of data fraud and other scientific misconduct, and as a result of numerous examples of violations of human rights in research such as those committed in the Tuskegee syphilis study where subjects were never told they had syphilis and were never treated for it.  

The Food and Drug Administration has had GCP regulations in place since the 1970s and these were expanded in 1997 with the addition of E6 GCP to the Federal Register. E6 GCP states that individuals performing clinical research must be qualified by training and experience (21 CFR 312.53: Selecting Investigators and Monitors; ICH E6 5.18.2: Monitoring; ICH E6 5.5.1: Trial Management Data Handling, Record Keeping), although specific standards of GCP training are not referenced. 

Pharmaceutical companies initially responded to E6 GCP by placing more emphasis on implementing GCP training for investigator sites. Basic training was (and is) offered at investigator meetings, but it often includes nothing more than a high-level overview and, because it is often time constrained, it may not include all of the critical elements. There is typically no knowledge check or completion documentation at the end of these sessions, so it may not qualify as GCP certification.  

As the need for improved GCP training was recognized, many pharmaceutical companies developed intensive, instructor-led, in-house courses for their clinical operations staff. Although many of these courses included practical application exercises, there was often no knowledge check, so the value was greatly diminished. This is also a costly method of instruction for companies if decentralized staff members are expected to attend in person. For this reason, many companies progressed to web-based programs or other methods of training for both investigational and operational staff. In addition to in-house or web-based instruction, sponsor companies and CROs may use an independent GCP training consultant to implement company-specific GCP training or may send staff to a clinical research, professional society, or commercial training course. Some companies offer only a slide review followed by a knowledge check to document their training.  

Current GCP expectations are that principals investigators and sub-investigators are trained in GCP and that this training is documented and tracked. It is expected that sponsors' clinical operations staff members are also trained in GCP, but there are varying requirements for refresher courses, documentation, and tracking. Regulatory agencies may have a reasonable expectation that clinical staff members are GCP-qualified, but currently there is no guidance that specifically defines what topics GCP training should include.  

Typically, courses available from professional societies include topics such as the history of GCP, sponsor and investigator responsibilities, informed consent, good documentation practices, safety, essential documents, audits, and inspections. This training is often static and may not cover current issues related to evolving technology, security/confidentiality, corrective and preventative actions (CAPA) and recent agency warning letters. Additionally, there is no defined time frame for refresher training, which can be a valuable component of actually delivering GCP. Ideally, refresher training would provide updates from practical audit and inspection experience such as warning letters as well as new regulations and regulatory guidance.  

There are many challenges involved with effective GCP training, not the least of which are adverse effects on sponsor/staff relationships that can occur when staff members are required to complete different GCP courses for multiple sponsors. With time frames for start-up decreasing, ensuring completion of GCP training can be a factor that delays the start of the study.  

If GCP training is to keep pace with the ever-changing regulatory environment, a method of standardizing its implementation must be developed that can answer questions such as these:  

Is it acceptable to just offer a GCP course once at the time of onboarding or must refreshers be required? 

Who is responsible for documenting the training and what is the appropriate amount of documentation needed?  

Is it enough to provide a completion date or should participants be tested? 

If they are tested, what is the passing threshold?  

Who is the appropriate audience for GCP training? Should study coordinators, medical writers, data management staff, and people fulfilling other roles involved with clinical trials also be trained?  

To solve the inconsistencies in GCP training, a centralized group representing global regulatory agencies and clinical research associations should be charged with designing and implementing a standard GCP course that can be offered to all appropriate individuals across all regions.  

A web-based course that includes comprehensive testing and practical application scenarios could work best. All parties would have access to the training 24/7, and the course would be updated as new information becomes available. To make sure GCP training remains effective, a standard interval for retraining would be established and maintained through a central database. Investigator and site staff as well as clinical operations staff would benefit by completing and being certified in a single course that applies to all studies from all sponsors.  

A standardized methodology is more efficient on many levels, including cost, scheduling, and time invested in completing the training. The initial cost to develop the standard training may be high in order to satisfy requirements of all countries and regions, but the downstream benefit is incalculable in terms of reduced training time, standardization of knowledge, and credible certification of clinical staff available to all sponsors.  

Since its inception in 1990, the ICH has evolved the standards that constitute GCP. The ICH could be the logical international body to take the steps necessary to design and implement a universal GCP training program and a global database of certified clinical personnel. 

— Jeanne Green is Senior Director of Clinical Operations and Janice Stack is the Training Director both at ExecuPharm.

The primary objectives of GCP are to protect the safety, rights, and welfare of subjects, and to ensure the credibility of trial data and resulting reports.

The Case for Universal GCP Education

Since the 2008 financial crisis knocked the global macroeconomic environment off of its feet, clinical research organizations in biopharmaceutical and medical device enterprises faced significant challenges as they entered into a new operational realm. Investors have scrutinized biopharmaceutical and medical device enterprises to operate more efficiently, strategically, and cost effectively in the new economy. Moreover, increasing global competition from generics and a glut of expiring patents have forced many biopharmaceutical and medical device companies to rethink their operational strategies.  

Large biopharmaceutical enterprises have divested from existing R&D models, and have paid top dollar to acquire other companies that offered diversified medical product portfolios in their pipelines. For example, in 2009 Pfizer acquired Wyeth for $68 billion, Merck acquired Schering-Plough for $47 billion, and Roche acquired Genentech for $47 billion. In addition, these companies pursued acquisitions in an attempt to mold into the new economic model, which requires cost efficiency, scalability and medical product portfolio diversification on the bottom line, and geographic expansion on the top line. As a result of changes in strategic directions and acquisitions, the biopharmaceutical industry made job cuts in order to consolidate operations. From 2008 to 2010, the pharmaceutical industry laid off over 157,000 employees. While the number of laid off R&D personnel is not confirmed, it is estimated that approximately 8,200 R&D personnel were laid off around that time period (1).

An unfortunate crux of the outcome of the financial crisis is that remaining staff supported lost resources from job cuts, as labor productivity rose on an annualized rate from 0.6%, 2.9%, and 3.1% from 2008 to 2010, respectively. Others left their organizations to seek further opportunities; in a recent poll, 43% of clinical operations respondents indicated that they left their roles because of too many organizational changes, and 29% needed more challenges in their roles (2). Complications associated with staff turnover involve the loss of intangible value that is affiliated with the process. A research study discovered that staff turnover, particularly in the services sector, results in the cost of over 150% to 200% of a staff's annual salary, (3), and 500% of a staff's annual salary for highly skilled professionals, (4). To elaborate, since the nature of clinical trials is highly dynamic, there is a heavy dependence on human skills, which involves specific areas of study expertise, strategic decision-making capabilities, GCP knowledge, and clinical trial business process experience, which attribute toward the cost impact of staff turnover.  

While the clinical trial industry relies heavily on human skills, clinical trial technologies and federal regulations have been changing to address industry challenges. Many cloud-based and IT solutions are emerging; these solutions integrate data from a variety of sources and offer enhanced insights and data visualization capabilities in one place. Furthermore, FDA's new guidance on risk-based and centralized monitoring enables clinical trial organizations to practice novel and efficient monitoring methods. The guidance encourages centralized monitors to undergo statistical training, (5).  

With drastic changes in biopharmaceutical and medical device strategic initiatives, reform in federal regulations, and the introduction of novel IT systems, clinical trial personnel need to be prepared to fit into the new clinical trial model.  

In the early-mid 2000s, there was a boom in clinical-IT systems and data collection solutions. While these tools offered management some insights, they were not as effective and comprehensive as today's IT solutions. Today's clinical-IT solutions not only integrate data from multiple sources, but offer breakthrough and customizable visualizations, real-time data, and cost efficient resolutions in order to assist clinical teams with decision-making. Many enterprises are releasing system-based to cloud-based clinical-IT solutions.  

Some biopharmaceutical companies have gone as far as fully leveraging IT solutions to implement virtual clinical trials. Pfizer, for instance, conducted the first fully virtual clinical trial "REMOTE" in collaboration with the FDA, where patients were consented electronically, medical products were sent directly to patients' homes, and patients were to conduct virtual doctor visits. This breakthrough trial design and platform seemed to have worked except for lagging subject recruitment activities, which depended on social media, (6). While subject recruitment was deemed unsuccessful by some, Pfizer indicated that they will use this model in future trials. 

Albeit clinical-IT innovation is exciting, clinical trial personnel are not yet equipped with the appropriate skills to analyze and comprehend IT offerings. In sponsor outsourcing, for instance, data visualization and insight misinterpretation can led to suboptimal decisions. As interviews with a clinical project manager indicated, their group misunderstood a data visualization, which identified enrollment under performance at several sites, and the group, subsequently, spent a significant amount of resources on unnecessary activities. The visualization merely suggested that the site was lagging in subject enrollment, and proper interpretation would have led to enriched decision-making. 

With changes in clinical trial analytical technologies and the need to find efficient and cost-effective operating models (as they relate to scalability), come opportunities to outsource many of the clinical trial functions that were previously internalized, such as site payments, data management, biostatistics, PK/PD, and regulatory document/records management functions. From 2009 to 2011, outsourcing expenditures to CROs increased by 6.6%, and in-house R&D expenses associated with internalized clinical operations reduced from 74% to 62% from 2010-2011, (7); this trend is likely to continue in the future. Moreover, some sponsors have formed long-term strategic partnerships with CROs and have integrated their business intelligence/IT capabilities in order to enhance productivity; Roche, for instance, partnered with Quintiles, which recently launched the Infosario platform that offers data integration and visualization solutions. Also, Pfizer formed a strategic partnership with ICON to amplify innovation and reduce operational costs. 

While outsourcing has its advantages, the concept presents new challenges for sponsor personnel; outsourcing requires employees to be equipped with advanced skills and capabilities to perform their roles, such as centralized monitoring. Moreover, sponsors have embraced the outsourcing model as well.  

Unfortunately many disasters have occurred with the outsourcing model and subsequent reversals to insource due to a lack of advanced employee skill sets. In an interview with a clinical program manager, they mentioned clinical trial quality was unmanageable with its outsourcing model, and that the group resorted to re-insourcing activities, which included site monitoring, resulting in higher costs, duplicative efforts, and lower productivity. This example demonstrates that suddenly changing strategies from outsourcing to insourcing without redesigning outsourced organizational structures to support re-internalization exhibits ruining effects on business productivity and financial sustainability. For sponsors, one of the most important facets in implementing the outsourcing model is to ensure that personnel are properly equipped with skills to operate within this model, including analyzing and interpreting data and overseeing outsourced activities via risk-based and centralized monitoring practices. 

Though the outsourcing model is not right for every company, as more enterprises start adopting the model, sponsor clinical operations personnel will need to hold necessary skill sets in order to efficiently oversee and manage CRO clinical trial activities. The new sponsor role is not to conduct day-to-day clinical trial responsibilities, but to be more accountable by making business decisions and enhancing quality management through efficient oversight. Further, with the increasing availability of insights and data visualization solutions, clinical trial personnel will not only need to exhibit clinical research expertise, but also demonstrate statistical, mathematical, business and financial expertise, and strategic decision-making capabilities in order to analyze data, interpret visualizations, and make optimal business decisions to efficiently resolve their dynamic clinical trial situations, accordingly. 

While the FDA released detailed guidance on risk-based monitoring, many clinical operations personnel have expressed confusion as to how they are to conduct risk-based monitoring assessments. Part of that bewilderment includes a lack of familiarity with qualitative and quantitative risk assessment techniques. In addition, despite the availability of data integration capabilities, many sponsor IT systems require personnel to perform manual data integrations in order to obtain customized visualizations that fit unprecedented situations. By equipping employees with the appropriate skill sets, clinical operations personnel could fully leverage the benefits of the outsourcing model.  

Clinical trials have entered into a new realm. With scrutinizing investor expectations, the amelioration of IT-system capabilities, the introduction of the outsourcing model, globalization, and changing FDA regulations on risk-based and centralized monitoring, existing clinical personnel need to be equipped with business operational/analytical skill sets, and new recruits must exhibit not only clinical, but analytical/statistical capabilities in order to successfully operate in newly-transformed organizational structures that focus on productivity, scalability, and cost savings. 

—Moe Alsumidaie, President and Chief Scientific Officer, Annex Clinical

Alsumidaie can be reached at info@annexclinical.com, or found online at his website: 

Increasing global competition from generics and a glut of expiring patents have forced many biopharmaceutical and medical device companies to rethink their operational strategies.

Clinical Research in the New Economy

The Drug Information Association (DIA) is preparing to celebrate 25 years of training and education provision at its annual EuroMeeting. 

The focus of the special anniversary congress, to be held in Amsterdam March 4-6, 2013, will be on better public health protection, greater transparency of processes and the rational use of medicinal products.  

The 110 sessions will be divided into pharmacovigilance and regulatory affairs for products and devices, R&D, clinical trials, and other topics. The main presentations will cover implementation of the new pharmacovigilance legislative framework, as well as health technology assessment and the patient's perspective. 

"By 2013, the new pharmacovigilance directive will have been in place for almost a year. What still needs to be done or improved upon, and most importantly, are we getting what was initially expected? These are some of the key areas that the professionals attending the meeting will be able to learn about and debate," noted co-chairs Beatriz Vicén Banzo and Peter Bachman, PhD. 

"Other important topics to be covered include the falsified medicines directive, the information to patients (what is the status?), the role played by scientific societies as experts, and considerations of an aging population and the potential impact on hospitalizations," they stated. 

More than 3,000 people from 50 countries are likely to attend, and there will be over 200 exhibitors. Speakers will come from the European Medicines Agency, the European Commission, the FDA, and other regulatory agencies, and patient organizations will be actively involved. 

The opening session will include a panel discussion on "Public/Private Partnerships: Working Together in the Interest of Patients." Other sessions that are likely to prove popular include those about the latest scientific issues from the European Medicines Agency, GCP hot topics, Japanese regulations, and the new regulations in clinical trials in Turkey. 

One of the pre-conference tutorials will concentrate on analysis of safety data from clinical trials, and is designed to provide a basic understanding of the underlying methodology and the current guidelines on safety data. Aspects related to the planning of clinical trials, as well as the problems and pitfalls encountered during the analysis of safety data, will be presented. Some case studies will also be discussed. 

"Amsterdam is the ultimate 'small big city' and combines all the advantages of a cosmopolitan capital with a compact, easy-to-navigate size which translates into less time spent commuting and more time enjoying what the city has to offer," pointed out Vicén, head of the public affairs and technical department at Bayer Spain, and Bachman, chair of the Coordination Group for Mutual Recognition and Decentralised Procedures. "The city has a rich cultural heritage and 2013 is a year to celebrate important events there." 

In addition to the 400-year anniversary of the Canal Ring, next year will see the re-opening of the renovated Rijksmuseum, the 125th anniversary of the Concertgebouw (concert hall) and the Royal Concertgebouw Orchestra, the 225th anniversary of Felix Meritis conference and event center, and the 175th anniversary of Artis Royal Zoo. 

The Rijksmuseum will not be fully open during the EuroMeeting itself, but between now and its re-opening on April 13, 2013, the masterpieces of the Dutch Golden Age will be on view in the Philips Wing. From April onward, the Rijksmuseum will be the first major national museum in the world to be open to the public 365 days a year. For more information on the DIA EuroMeeting go to bit.ly/SGL9WS. 

The Drug Information Association (DIA) is preparing to celebrate 25 years of training and education provision at its annual EuroMeeting.

DIA EuroMeeting Gets Set for 25th Anniversary

The end of the highly acrimonious election campaign has signaled a shift by policy-makers and interest groups to focus on dealing with the so-called government "fiscal cliff:" nearly $500 billion in tax increases and spending cuts are scheduled to kick in January 1, 2013 under an authorized "sequester" process unless Congress acts quickly. With Republicans maintaining tight control over the House of Representatives but losing ground in the Senate, much depends on the ability of President Obama to engineer some kind of fix to the mounting deficit during the year-end "lame duck" Congressional session—or for the White House and Congress to agree on delay and leave major budget decisions and tax reform for next year. Whatever the strategy, the outcome promises to have a major impact on federal funding for the Food and Drug Administration, the National Institutes of Health, and government healthcare programs such as Medicare and Medicaid. 

Health policy was a key point of dispute during this past year's political contest, marked by promises of better coverage and warnings of soaring costs by both candidates. The Obama victory ended prospects for wholesale repeal of the Affordable Care Act (ACA) and spurred the Department of Health and Human Services to forge ahead with new rules and policies for establishing insurance exchanges, defining benefits, and expanding Medicaid. Those initiatives require action by the states, which have been reluctant to commit to new programs during a period of political uncertainty, but now face important go/no-go decisions. House Republicans will continue to challenge specific requirements of the health reform program, but key provisions for pharmaceutical companies, such as rebates on drugs for seniors in the Part D coverage gap and authorization for biosimilars, are unlikely to change.  

Most important for the development of new drugs and medical products is the promise that Obamacare will provide coverage to some 30 million previously uninsured Americans and, consequently, significantly expand the US market for innovative medical treatments. Although all sides acknowledge the imperative of reducing both public and private outlays for US healthcare, important therapies that can document value for patients are likely to gain coverage from plans and payers.  

That said, drug prices and reimbursement are a prime target of cost-cutters, particularly related to outlays for federal government health programs and Medicare drug plans. House Democrats have pressed for added rebates on drugs purchased by Part D plans for low-income "dual eligible" seniors, which could total more than $100 million over 10 years, and policy-makers are considering a range of options for reducing federal spending on prescription drugs and high-cost biologics.  

Executives at biopharmaceutical companies are well aware that these tax and spending proposals will shape investment in medical innovation, but also are involved in a campaign by the business community to orchestrate significant reforms in corporate taxation to make US firms more competitive in the global economy. The difficult trade-off for industry leaders is that efforts to avoid looming tax increases and gain fiscal reform would require broad budget cuts that curb government reimbursement for medical products and squeeze resources at federal agencies.  

The Obama victory offers a degree of stability for FDA, NIH, and federal health programs. It avoids a wholesale change in executive branch leadership, although many top administration officials are likely to move on.  

Yet, budget cuts would undermine R&D and regulatory initiatives. FDA could face delays in implementing the FDA Safety & Innovation Act (FDASIA) and its provisions to accelerate approval of new breakthrough therapies and much-needed treatments for infectious diseases and rare conditions. An 8.2% reduction in the FDA budget, as proposed under the budget sequester process, would reduce FDA's 2013 budget by $320 million and prompt the agency to lay off about 1000 employees, according to consultant Steven Grossman. Even without such a severe drop in funding, Grossman fears that the FDA budget will remain vulnerable to pressures to reduce federal spending for some years to come. 

Parexel CEO Josef von Rickenbach says he's more worried about funding for NIH than for FDA, which he considers "such a public agency that the administration can't really unfund it without serious consequences." But NIH, von Rickenbach notes, "provides vital support for discovery that is important for small biotech companies." Severe budget reductions could jeopardize its recently expanded translational research programs that promise to spur innovation to fill depleted new drug pipelines. ­

The end of the highly acrimonious election campaign has signaled a shift by policy-makers and interest groups to focus on dealing with the so-called government "fiscal cliff."

Administration, Congress Face Challenges in Funding Biomedical Research, FDA Initiatives

The 2008 Salary Survey: Now With Web-Exclusive Charts &Figures

2006 Survey of Wages and Job Trends in the Clinical Trials Industry

Statistics and headlines don't portray a pretty picture ofthe economies in Europe or in the United States. Adding in the next layerspecific to the clinical research and trials industry, and the picture inthe past two years continues to be complex and changing. It is not just oneforce—the economy—at play. Other aspects include spikingregulatory requirements; increasing global complexities; and the diminishingblockbuster drug model. 

But the economy is certainly applying more than its fair shareof pressure onto the conduct of drug development. The other dimensions arethe technologies, outsourcing strategies, and mergers and acquisitions thathave resulted from the downward forces.   

Annual job losses in the overall pharmaceutical industry inNovember 2011 were 20,000, which were significantly lower than the cutsposted from 2010's 50,000 number. The pharmaceutical industry rankedsixth on the 2010 list of annual job-cut rankings, below government,financial, retailing, aerospace/defense, and healthcare.    

For the time period January 2011 to July 2011, thepharmaceutical industry shed 18,264 jobs and for the same period this year8,968. And while the reasons for job cuts were not cited by individualindustries in the early August Challenger, Gray & Christmas jobs report,the top five reasons for job-cutting across industries are: restructuring,closing, cost-cutting, economic conditions, and loss of contract.  

However, while job cuts may be leveling off in thepharmaceutical industry, planned hiring is not in the cards. In the jobsreport, for industries planning to hire, pharmaceuticals were in the bottomthree. In fact, in another report, earlier this year, smaller to mid-sizebiotech companies were the ones more likely to predict growth versusone-third of larger companies. In an Aon Hewitt report, less than 5% of thesmall- to mid-sized biopharma companies expected their staffing to decrease,compared to 15% of the larger sponsors. 

With all of the downsizings, and seemingly less or non-growingstaff to handle the workload, the larger pharmaceutical companies are taskedwith merging internal capacities, weeding out redundant departments andpositions, and figuring out what to do with the capabilities in which theywill no longer invest. Among these companies, outsourcing is the key togetting work done.  

In a January 2012 Annual Global CEO Survey fromPriceWaterhouseCoopers, it found that 43% of biopharma CEOs had outsourced abusiness process function in 2011. This compares with all other industries,where CEOs reported 35% to the outsourced business function question. 

conducted in August, results found the following top threeoutsourced functions: full-service CRO, 41.3%; monitoring, 21.7%; andsubject recruitment, 13%. 

All of this outsourcing activity translates into additionaldownstream trends. The first is the ability of both the sponsor and itsoutsourced partner to effectively manage the outsourced relationships. Andsecond, is that it could mean a boon of sorts to contract researchorganizations. 

Both trends come to light in separate surveys. The first weconducted in August, where we asked: "Has your need to provideoversight of these sourcing relationships changed over the last twoyears?" The responses were weighted toward a definite increase at 62%.

And the second trend, what it means to CROs, the Salary andCareer Development Survey conducted in September and October by CenterWatchand 

 found that respondents workingfor CROs were significantly more likely to see a positive change in theeconomy compared to sponsors or investigative site respondents. 

In his September 2012 column, Ken Getz offered a more targetedanalysis of the CRO market size in the United States. From Tufts CSDD data,it surmised a total of 21,000 US jobs in the clinical research segment; 643total companies, and the total share of US personnel comprises 13%worldwide. Its analysis, which includes regulatory services, has theclinical research market valued at $6.5 to $8 billion. Approximately 17% ofthe companies providing these services are publicly traded. 

In other reports, the forecasts are for growth in global CROmarket size and penetration. Business Insights forecasts the market to be$35 billion next year, and Frost & Sullivan anticipates Compound AnnualGrowth Rate of 10.5% through 2017. William Blair & Co. expects thecurrent outsourcing penetration rate to increase by a few percentage pointsover the next year or two, and CRO management commentary suggests that overthe next five to seven years the outsourcing penetration percentage couldincrease to more than 60%. Its model currently anticipates a 10% increase inpenetration from 2010 through 2015. What this all means is that pharma isrelying on CROs and service providers more than ever in its clinicalresearch.  

 has conducted the Salary andCareer Development Surveys on a biannual basis since 2006. For our surveysin 2010 and 2012, we partnered with CenterWatch to develop the questionnaireand analysis of the data. Their own report from this shared data will bepublished in their January/February 2013 issue. 

The 2012 Salary and Career Development Survey was conductedduring the months of September and October 2012.  The survey was conductedonline and was e-mailed to a broad range of clinical research professionalsworldwide (Figure 1). A total of 1,068 professionals responded to thesurvey. Close to three quarters of responses originated from the UnitedStates and the majority of the sample was employed full-time. A third of thesurvey respondents possessed a bachelor's degree as their highest levelof education completed and over half of the sample had some type of advanceddegree, indicating a highly educated group overall. Survey respondentsaveraged 15 years of experience in their profession and averaged seven yearswith their current employer (Table 1). The survey instrument contained avariety of questions relating to job satisfaction, job security, careerdirection, challenges in the work environment, and the economy's impacton careers and the clinical research industry in general. 

According to the CenterWatch research analyst conducting thepast two surveys, the 2012 results were largely very similar to the 2010survey—the sample composition was generally the same as the lastsurvey in terms of industry/type of business/years experience and tenure atcurrent company. The following differences will be highlighted in thisarticle:   

Overall, salaries have increased from 2010 to 2011. Theproportion of respondents who received supplemental income this past year isthe same as in the past survey. 

Table 2 and Table 3 show the positions for which we surveyed,along with the increases between the two years. Also, we surveyed changes byindustry sector, illustrated in Figure 3. All in all, there were increasesto median salaries even with the negative economic news. For US regions, thelargest gainer was the Northwest, followed by the Midwest, Northeast,Southwest and the Southeast, where median salaries remained static. 

With the losses and downsizings reported for the last threeyears, we asked respondents how secure they felt about their currentposition. Respondents in this year's survey were more optimistic aboutjob security compared to two years ago. A significantly higher proportion ofrespondents perceived their job security to have improved compared to twoyears ago (Figure 3). Once again, as with the overall economic view, whenlooking at the results by industry, respondents working for CROs weresignificantly more likely to respond that they were very secure in theircurrent jobs. 

For this response the changes between 2010 to 2012 werenon-existent. But, when asked about job security compared to three years agowith clinical research professionals in general, all respondents noted anuptick in the positive side of the spectrum.  

By industry, 42% of CRO respondents felt very secure with theircurrent employer, versus 31% of site respondents and 18% of sponsors. Thesenumbers improved greatly when checking the "somewhat secure"rating to 46% for CROs, 55% for sites, and 60% for sponsors.  

When asked about the security for clinical researchprofessionals for the past two years, the same industry sectors reportedsignificantly increased to 44% of CRO respondents; 35% for investigativesites; and 46% for sponsors.  

There is no mistaking that clinical trials have gone global,with no signs of turning back. While the current distribution of clinicaltrials registered on

 features most trials still conducted in the United States, Europe,and Canada, the current value for the outsourcing market in China is peggedat $400 million. 

Feature Article

The rocky economy continues to wreak havoc on employment and drug development.

2012 Salary and Career Development Survey

The constant refrain of European politicians is the urgent need to create jobs—no surprise in a continent with high and rising unemployment. Across the European Union, 25 million people were jobless this autumn, and in Spain and Greece there is now a quarter of the working population without jobs.  

Inevitably, the search is on for sectors that offer the best hopes of boosting employment—and healthcare is increasingly seen as one of the most promising sectors to examine. The pharmaceutical industry in Europe already sets a fine example. According to figures from its principal European federation, EFPIA, its members employed 660,000 people directly in 2011.  

Germany is the largest employer, generating more than 100,000 direct pharma sector jobs, and is closely followed by France, with 97,000. The United Kingdom and Italy come next, each with more than 66,000. And Spain, Switzerland, Poland, and Belgium each provide more than 30,000 jobs. Ireland, Hungary, Romania, and Denmark each generate more than 20,000 as well. 

Not only does the sector create direct jobs, but it generated three to four times more employment indirectly—upstream and downstream, says EFPIA. This is attributed largely to its research function, and, EFPIA points out, many of these indirect jobs are of high value, in areas such as clinical science or in academia. The presence of a highly-skilled workforce was one of the key factors in the industry investing €27.5 billion in R&D in Europe last year, it says. 

The industry story gets better and better, claims EFPIA. Direct employment has risen to its current level from just over 500,000 in 1990—something like a 35% increase in a decade. And at the same time, the number of direct employees in research has risen too—from 76,000 to 116,000, an even steeper rate of increase. 

Andrzej Rys, the director responsible for health systems in the European Commission (and one of the senior officials behind the proposal to update the clinical trials rules), has been extolling the merits of the healthcare sector as an employer, too. "Health professionals play an important role in the EU economy, accounting for about 17.1 million jobs," he said in a statement in November.  

Healthcare is seen as one of the most promising sectors to help boost EU employment.

Applied Clinical Trials-12-01-2012