All pharmaceutical companies seek to improve efficiency in clinical trials data collection; this is no less the case for Boehringer International (BI). 

Boehringer first approved the principle of using electronic data capture (EDC) in 2001, with the goal to evaluate the best technologies available on the market in order to see if we could further improve quality and our performance. At the same time, we needed to be careful to ensure that any changes would not affect quality regarding the management of clinical data. In addition, it was clear for BI that EDC had the potential to reduce the effort needed during the conduct of the study and to speed up the collection of clean data in the database. 

The RDC (Remote Data Capture) system Oracle Clinical (O*C) was chosen as our EDC tool, and we were therefore able to integrate our new clinical data with existing clinical trials databases. Because O*C is the clinical data management system that has been in use by Boehringer since 1997, the data management setup activities went very smoothly, since the study programmers were already trained to operate this application. Our target concerning RDC deployment is 100% of BI clinical trials by 2007. By the beginning of 2006, we were running about 40% of our trials in RDC. 

Savings Derived from Remote Data Capture			

The key RDC benefits identified were: 					

Early decision making; the information is processed and shared at the time of the data collection, eliminating the need to wait for the CRA's source data verification (SDV) monitoring visit.

Elimination of paper queries back to site; data validation is performed during and just after data entry.

Investigators save time, primarily in dealing with discrepancies.

Better quality of the data; the data are cleaned just after data entry (see Table 1). 

Information is shared remotely with all of the clinical study staff at the site and sponsor levels, so everyone sees the same view of the data.

Reduced time frame between the last patient out and database lock.

Boehringer has hired a vendor, Hewlett Packard (HP), which is in charge during the start of the study of checking that the Investigator's sites have appropriate equipment, Internet connections, and BI notebook deployment if needed.  

Furthermore, HP also acts as a hotline, an RDC helpdesk, which during the conduct of the study offers assistance 24 hours a day, seven days a week in English and five days a week in German, French, Italian, and Spanish.  A "language line" is used to provide translation service in about 120 different languages. 

Boehringer has chosen to develop a Web-Based Training (WBT), program to complete the RDC training, which is accessible with an Internet browser. The training includes interactive simulations, quizzes, and useful illustrations and tips. 

Two different user groups were identified for this training, the Site Users and the CRAs. At the end of the course, the trainees have to print a certificate, which is mandatory to obtain a SecurID token and password, and thereby access to the study. 

It is not simple to give direct evidence regarding savings and costs, but we can observe some indications. We have separated two approaches of savings—the visible and the derived. From my point of view, the derived savings are the most important. 

We have encountered certain technical hitches along the way, such as unavailability of Internet connection on site and issues concerning on-site internal security measures (firewall configuration, etc.). Issues such as these, however, will in the future likely be remedied by the further roll out of wireless technologies.  

One of the crucial factors for the success of RDC implementation at BI has been the holistic approach we applied to the integration with our existing CDMS. Our client-oriented focus, such as the suite of user-friendly RDC software, clear Web-based training, and helpdesk availability, has also been a key contributing factor. 

We remain convinced that RDC is an effective tool to improve the quality and efficiency of our clinical data and is here to stay. 

 is head of data management and clinical trial support with Boehringer Ingelheim France, 12, rue André Huet, B.P. 292, F-51060 Reims cedex, France.

Articles

Notes from the Field

Boehringer International implemented a holistic approach to electronic data capture, boosting quality and efficiency.

The EDC Decision

Paediatric Clinical Research Manual Edited by Professors Peter Helms and Peter Stonier (Euromed Communications, 2005), 700 pages, loose-leaf binder with annual update and two annual supplements, ISBN: 1750-063X, $684.00, Europe €520.00, ROW €535

 to review was that its publication was particularly timely, given that the EU Regulation relating to research in children is due to become law late in 2006. However, as I read it, I felt that to have delayed its release until the final content of the Regulation was known would have perhaps been better, as several of the chapter authors were speculating about exactly what it would mean for pediatric research in Europe, and in some cases they were already out of date. It could be that the production of the book took longer than expected, accounting for what seems a strange time to publish such a work. The good news is that the format is ring bound, and I hope that the publishers plan a very prompt update for the relevant chapters. 

Certainly the scope of the book is wide and the area very thoroughly covered. Topics range from clinical pharmacology to prescribing, and include regulatory issues in Europe, the United States, and Japan; ethics and law; study design and conduct; and how to make sense of it all. Overall I found it to be well thought out, with a very high level of valuable content.  

Several authors described very clearly the particular difficulties and challenges of research in children, in particular the need to start anew with specifically designed protocols and not merely to adapt one already in use for adults. The creative ways in which one can avoid frequent blood sampling, bearing in mind both the small blood volume of a child and their hatred of needles, were explored in detail.  

McLean's chapter was for me one of the most useful, describing the legal and ethical aspects of research in children. Her conclusion could stand for the whole book: "The need for paediatric research is irrefutable; the problems of conducting it are immense."  

The chapter by Landgraf on health-related quality of life was excellent—well-written and argued. It was one of a few chapters that included a reading list of additional sources not already quoted—a very useful extra. More difficult to read, but a really excellent reference document, was the chapter by McElnay and Chaw—complete with 161 references! 

There were downsides, too, quite apart from the timing of publication. I may be pedantic, but there was some gruesome mangling of English grammar ("the teeth...was"), some contradictions between chapters (2003 or 2004 for the relevant pediatric Regulation?), and more repetition than was perhaps needed. Several authors used "children are not small adults," as if their own invention (three times in one chapter), although one had the grace to use inverted commas! It may well be that each chapter is intended to be able to stand alone, but more use of "please refer to chapter X" and less repetition verbatim might have made for an easier read. Inaccuracies of fact such as the description of the Gillick case (relating to the competence of children to consent) were also irritating.  

The thorny issue of equipoise was raised in more than one place, yet the definitions seemed to vary. One author claimed it meant that nobody could determine which study arm the subject would enter, and another that it meant that half the trials would favor one treatment and half the other. (My understanding is that equipoise means not knowing the outcome of a study during its design and conduct, but I am happy to be corrected.)  

are superbly referenced, but there were some areas where a well-placed reference would have been helpful. In the foreword, for example, there were examples of deeply unethical trials. A reference would have allowed the interested reader to follow these up and read more. Nicholson too, while writing well and fluently, denies the reader support for his statements.  

Overall this is a very good and helpful book of value for anyone working in drug research. We must all be comfortable with research in children, whether we want to or not; it is no longer possible to avoid it. There is a need for training within the industry and among clinician researchers, and this very readable and wide-ranging book—if kept suitably updated—is a very helpful source of support.  

 FFPM, is medical adviser and director of MedicoLegal Investigations Ltd., PO Box 490, Cambridge, CB3 6XB, United Kingdom, telephone and fax +44 (0) 1438 820000, email: 

Media Review

A review of Euromed Communications' recently published: Paediatric Clinical Research Manual

Training in Pediatric Research

The market for managed site networks has been quietly and steadily changing during the past five years. With the exception of Radiant Research, classic site management organizations (SMO) appear but a remnant of their former selves. At the same time, new decentralized site networks have taken a dominant position within this small—and shrinking—study conduct segment. Given widespread and rising levels of sponsor–site relationship ineffectiveness, it is critical that biopharmaceutical and CRO companies understand how managed site networks are evolving in order to more effectively manage collaborations with this particular service provider. 

Sponsors are spending less on managed site networks in favor of individual part-time and dedicated investigative sites, a reversal of the trend observed in the late 1990s and early 2000s. In 2006, research sponsors will spend in total an estimated $7 billion on study grants to investigators. This level of spending has grown 10.7% annually since 2000. In that same period, spending on study conduct services provided by managed site networks—including SMOs—has grown only 2.5% annually, from $281 million in 2000 to $325 million in 2006. 

This year, community-based part-time and dedicated investigators capture 56% of the market for investigator grants; academic center-based investigators capture 39% of the market. Managed site networks capture only 4.6% of the total study grant market, down from 7% six years ago. Despite all of its promise, traditional SMOs never fully took hold in a study conduct market characterized by fragmentation and high levels of inefficiency, and one that lacks sophistication and standardization. So what happened? 

In the mid-1990s, SMOs appeared well positioned to meet growing demand for faster development cycle times, improved data quality, and controlled clinical trial costs. Few argued with the numerous conceptual benefits offered by SMOs including: 					

Standardized contracts and operating procedures

Systematic management of patient recruitment and retention

Streamlined regulatory and legal review and approval processes

Reduced fixed costs to offer more competitive pricing

Applied business and management principles

But since their introduction 15 years ago, SMOs have struggled to deliver on these conceptual promises and have been through a wide variety of incarnations. The first SMOs emerged under a cloud of scandal, when Future HealthCare, an early entrant, was indicted for manipulating its financial records in order to influence investors. 

The mid-1990s saw a wave of new entrants—owned-site and affiliation model SMOs offering single-and multi-specialty expertise—including Affiliated Research Centers (ARC), Clinical Studies Limited (CSL), Collaborative Clinical Research, Hill Top Research, Health Advance Institute (HAI), InSite Clinical Trials, Protocare, Integrated Neuroscience Consortium (INC), Rheumatology Research International (RRI) and several hybrid CRO/SMOs such as Clinicor, MDS Harris, and Scirex. 

In the late 1990s, SMOs entered their most active period of venture capital fund-raising and aggressively pursued expansion and diversification strategies. Collaborative Clinical raised $42 million in a 1996 initial public offering. ARC, INC, InSite, and HAI each closed rounds of venture capital financing. Phymatrix, a $200 million physicians practice management group, acquired CSL for $85 million. nTouch Research (formerly Novum) raised $8 million in venture capital funding in order to double the size of its investigative site network through the acquisition of HAI. And having raised more than $14 million in 1999, Radiant Research purchased SMO Hill Top Research. 

By the early 2000s many SMOs had exited the market, while others further diversified their services, venturing into traditional CRO and patient recruitment offerings. To name but a few: 					

 following a public offering and announced that it would be exiting the SMO business to become a provider of electronic clinical trial technology solutions.

 focused their attention on offering CRO services.

 (formerly ARC) abandoned its SMO services in order to focus on offering contract patient recruitment services.

 shut down its operations in 2000 after selling four of its seven sites to 

, which had hoped to expand its regional network of eight owned sites, also exited the business in 2000.

—another top five SMO—in 2003, expanding their network to nearly 60 sites.

With the exception of Radiant Research, industry observers and scholars have concluded that traditional SMOs failed to demonstrate and deliver the value of centralized investigative site operating controls. SMO management structures were cumbersome and challenged each organization's ability to operate profitably for a sustainable period of time. Traditional SMOs struggled to compete for sufficient levels of new business and manage positive cash flows, and they failed to achieve revenue and earnings growth that would satisfy their investors. 

SMO insiders express the failures of traditional SMOs differently. "Trial sponsors never gave SMOs the opportunity to prove their worth," explained Eric Hayashi, chief executive officer of LabConnect and former head of business development for Radiant Research. "Sponsors have an investigator-centric method of selecting sites. Changing that purchasing behavior is difficult given the paucity of successful SMOs. Only a few brave sponsors ever relied on an SMO to manage an entire study." 

"Many owned-site SMOs went into this business with the belief that they could wring excessive expenses out of large, successful sites run by frugal physician entrepreneurs," added Hayashi. "Instead, most SMOs added layers of administrative burden that ultimately made them less profitable." 

"I agree that sponsors want to deal directly with the investigator. As a result, there's little glue holding SMOs together," said Mark Hovde, senior vice president of marketing for Mountain View, CA–based Pharsight. "Once a sponsor is introduced to a good site, it sees no reason to keep paying the middleman." 

"Site selection and management was always a problem for SMOs because performance was predicated on so many variables, including staff turnover and the competitive landscape," said Beth Harper, a Dallas, Texas-based consultant and former manager of operations for RRI. "Half the problem is that SMOs could never reach a consensus on contract language and definitions, leaving sponsors unable to understand what an SMO does." 

The past several years have seen strong growth in a new structure among managed site networks: decentralized site networks. The Tufts Center for the Study of Drug Development has been tracking this development. These new players tend to operate regionally and have extremely lean operations. They are comprised of small networks of sites—on average five—loosely connected and supported by minimal standardized management services provided across the network by one site, from which that network originated. Basic management services include contract, budget, and regulatory assistance. 

Although many decentralized site networks have established exclusive arrangements with their investigators, they encourage autonomy and direct interaction with study sponsors. As a result, they address sponsor's "investigator-centric" preferences while offering minimal—though essential—operating support. Examples of decentralized site networks include Pivotal Research, Benchmark Research, ResearchAcrossAmerica, and RxTrials. 

Decentralized site networks are building momentum. They generated $215 million in study grant revenue in 2006, and they are growing 9.3% annually. This highly fragmented group appears well positioned to capture growing market share over the next several years while containing operating costs. 

"Less venture capital and private equity funding means that sponsor companies are much more likely to see smaller, regional site networks like Pivotal and RxTrials take hold," concluded Hayashi. "Sponsors and CROs want to work more closely with the investigator and study staff, they want a responsive and effective relationship with fewer intermediaries. These [decentralized] site networks may be the next SMO."  

MS, MBA, is a Senior Research Fellow at the Tufts CSDD and Chairman of CISCRP, both in Boston, MA, email: 

Clinical Trial Insights

Yesterday's SMOs have given way to a new service provider that should be recognized.

Spotting the "New" Managed Site Networks

Developing an integrated project plan requires the involvement of experts from each of the functional domains. It is always good to set benchmarks from industry best practices within those domains. Best practices identified from wide experience in numerous clinical trials were incorporated in the New Chemical Entity (NCE) template described in Part One of this article (

, August 2006). Naturally, some task times will vary widely by product and indication, but a starting framework is a useful baseline from which to then later modify using more specific assumptions. Even with the variation from product to product, a standard best practices timeline can help set general expectations even before the detailed aspects of the preclinical or clinical development plan are known. Particularly in the clinical area, many tasks are fairly standard from one study to the next (e.g., four months to initiate a trial). 

Discovery research is by nature the most creative aspect of the process and is best managed with modest schedule constraints and maximum flexibility. The project template allows one year for Discovery activities. Following Discovery, the first detailed part of the project plan template is the Initiation Phase. Before a project can transition from research to development, it must be critically evaluated in the Initiation Phase for overall feasibility from the technical, financial, marketing, and resource perspectives. Once the project is approved to advance into the development domains [Nonclinical; Chemical, Manufacturing, and Controls (CMC); and Clinical], the work on manufacturing and formulating the Investigational Product (IP) may begin. Figure 1 shows a breakout of the Discovery pharmacology and proof of concept section of the template, and an overview of the steps for the project Initiation Phase. 

The CMC effort requires several years to produce IP at Good Manufacturing Practice (cGMP) standards, but early Nonclinical safety testing may be conducted using non-cGMP product that is usually produced within 12 months. Another 12 months are allowed for manufacturing to reach pilot scale process. The toxicology and early Phase I clinical studies require cGMP investigational product from pilot scale batches. CMC is often plagued with long lead times that can compromise development schedules and delay critical Nonclinical and Clinical milestones if there is inadequate advanced planning. As a result, it takes a dedicated effort to assure that manufacturing responds to development initiatives in a timely fashion. Getting into the queue for manufacturing the various batches of IP (laboratory scale, pilot scale, and production scale) can create months of delays if not addressed early. In addition, the manufacture of pilot and production scale batches involves extensive validation and quality control procedures that add significantly to the overall time requirements. An overview of the CMC section of the template is illustrated in Figure 2. 

 Figure 1. The templateÃÂ´s pharmacology and proof of concept section, and initiation phase steps.			

Once CMC has initiated its plan and there is confidence that the IP can be manufactured at the required scale and on time, more specific details from the Nonclinical and Clinical plans supplant the automatic defaults in the project plan template.  The safety studies in the Nonclinical module of the template are planned for completion in a few months and assume the use of unformulated, laboratory scale IP. Toxicology studies begin only after preliminarily formulated cGMP IP is available.  

Figure 2. Overview of the CMC section of the template.  			

CMC commonly is on the critical path for early Nonclinical studies, particularly toxicology studies. Once cGMP investigational product is available, most of the toxicology studies are finished within two years. Toxicology studies that are not required for Phase I and/or are very expensive (e.g., definitive carcinogenicity studies) are delayed in the template until they logically fit into the project plan timeline. In Figure 3, the major studies and elements of the Nonclinical template module are detailed. 

Figure 3. Major elements of the Nonclinical template module. 			

Subject enrollment in the clinical program is initiated 30 calendar days after IND filing. (All other days described below are work days per MS Project

 .) Human dosing at an investigational site begins when the following predecessor steps are completed: 1) protocols are written and approved; 2) the IND is accepted; and 3) IP is available at the site (requires completion of essential regulatory documents).  

Clinical studies usually follow the same basic operational tasks, no matter what product is being studied, and the template was designed with that assumption. Start-up tasks are generally similar between studies, although timelines expand with the number of sites involved. In practice, a single-site Phase I study could be scheduled and initiated with a single phone call, while a large global trial involving 300 sites would require more time. A complicated protocol or one in which investigative sites are not readily available might also require substantially more time. There are, of course, many other design variations other than the number of sites that might occur and affect study start-up timelines. For template consistency the Study Start-up module allows two variations in duration of time required to identify and select investigative sites: 1) a Phase I and pharmacokinetic-type trial is set at 23 days; and 2) a longer Phase II and III timeline is set for 52 days. An example of the Study Start-up module in a Phase I trial is shown in Figure 4. 

Figure 4. Example of the Study Start-Up module in a Phase I trial. 			

In the Study Conduct module, two enrollment rates and three "on-study" durations were allowed for subject enrollment and treatment defaults. This keeps the template for the Study Conduct module standardized and reusable, but modifiable when more specific study information becomes available.  					

Phase I and pharmacokinetic-like studies allow for enrollment over 20 days from "First Subject In" (FSI) and "Last Subject In" (LSI) and one day on-study. 

Most other studies (Phase II and Phase III) use a 60-day enrollment window for FSI to LSI and 60 days on-study. 

Safety studies are usually longer term and the module provides for 60 days for FSI to LSI and 260 days on-study.

A breakdown of the Study Conduct module for Phase II and III studies is illustrated in Figure 5. 

Figure 5. The Phase II and III Study Conduct module is standardized, yet it can also be customized.			

The template defaults to a Phase I program duration of approximately 12 months assuming that most trials will be conducted in parallel. It allows for some pauses and delays to modify trial designs based on information learned as the development process proceeds. The basic Phase I program has a test of concept protocol and four other protocols required for single-and multiple-dose tolerance studies and pharmacokinetic evaluations.  

The template assumes a Phase II program duration of approximately two years. A typical Phase II program involves 20 or more studies to test for safety, biodistribution, and drug interactions and to demonstrate initial efficacy and dose response. Many Phase II studies can be conducted in parallel and resemble pharmacokinetic-type trials rather than longer and larger efficacy trials. A high-level overview of a broad Phase I, II, and III clinical plan in the template is shown in Figure 6. 

Figure 6. High-level overview of a Phase IâIII Clinical Plan. The End of Phase II FDA Meeting is critical.  			

A critical regulatory deliverable in the middle of the clinical program is the "End of Phase II Meeting" with the FDA. Usual discussions with the FDA focus on information obtained in the first two Phase II studies in the template: the pilot efficacy study and the first dose response study. These two studies deliver the bulk of information necessary to plan the major components of the Phase III protocols and prepare for the End of Phase II meeting. Completing the End of Phase II meeting milestone triggers the start of Phase III planning and completion of operational work steps while the rest of the Phase II studies continue. 

Phase III is usually the longest clinical phase due to the size and duration of the trials. The template allots three years for this clinical phase, which includes two well-controlled trials and a long-term safety study. Final compilation of the CTD submission begins immediately following completion of the long-term safety study in Phase III.  

Figure 7 highlights some of the typical durations for major components of the plan and lists key predecessors that may need to occur prior to beginning that task or activity. 

Figure 7. Typical plan component durations and the predecessors necessary prior to beginning tasks.			

Since all R&D activity is ultimately designed to meet the obligations of regulatory authorities, every project plan task in the template feeds into one of the five primary Regulatory deliverables: 1) the pre-IND meeting; 2) the IND submission; 3) the End of Phase II Meeting; 4) the pre-NDA/CTD Meeting; and 5) the NDA/CTD submission. Using MS Project

 , the operational tasks embedded in the template and required by the Regulatory domain are made dependent upon completion of upstream tasks by the other functions. The schedule is kept coherent through a regulatory backbone composed of IND and NDA requirements. The backbone extends through the postsubmission time frame and includes recurring requirements such as IND Annual Reports and CTD Safety and Periodic Updates. The content outline for the CTD is shown in Figure 8.

Figure 8. The templateÃÂ´s regulatory deliverables outline helps keep the project on track.			

Any size company may achieve project acceleration through utilization of a plan. Large pharmaceutical companies with multibillion dollar R&D budgets are often envied for the financial resources they can apply to a particular problem or hurdle, but ultimately they have little advantage over any size company conducting a well-managed project. Smaller teams are often as effective as large ones in tackling complicated projects. Small teams communicate quickly, make changes more easily, and adapt to changing information readily—leading to faster progress overall. The detail of an NCE template can be used to great advantage by the project team during implementation of specific operational drug development strategies, including project acceleration through outsourcing and establishment of fast-cycle performance.  

Outsourcing is an acceleration tactic that especially benefits smaller companies. A detailed and fully integrated project plan (or evolving plan in a completed template) is a key to outsourcing any project activity effectively and communicating clear expectations to outsourcing partners. Outsourcing may be strategic or tactical. Strategic outsourcing implies that outsourcing decisions are made for the entire R&D portfolio to assure that priority projects receive appropriate internal and/or external resources. Tactical outsourcing is transacted by the project team or functional department. It usually involves only certain elements of the operational activity, which is delegated to specific outsourcing partners. These partners perform narrower functions and have developed an expert niche, such as nonclinical studies, specialized manufacturing, designing pharmacokinetic protocols, recruiting and prequalifying clinical study sites, data collection and analysis, auditing/QA or medical writing.  

An evolving project plan embedded in a complete and detailed template assists the project team, or functional departments appropriately delegate blocks of project activities to appropriate outsourcing partners and still manage those activities successfully. In the template, the tasks have standardized names, which facilitate communication inside and outside the outsourcing company. The template alerts the project team to minute detail where the partner must perform per timeline to stay off the critical path, where the partner and company need to communicate and interact, and where achievement of milestones allows comparisons of the partner and the company's own internal performance against recognized industry benchmarks. 

Project planning and fast-cycle performance

Another strategy to accelerate projects that requires a very detailed, complete, and integrated project template is fast-cycle performance. Fast-Cycle Teams (FCTs) are usually implemented to surmount normal company processes that would otherwise delay a critical project. FCTs work outside the traditional company hierarchy and are empowered to make project decisions that will move the project forward.

  In the "tiger team" variant of FCTs, team members typically come from the highest ranks in the company: vice presidents and directors. They take sabbaticals from their R&D functional responsibilities for the duration of the project and streamline Standard Operating Procedures (SOPs) to maintain project quality and increase project speed; tiger teams are not required to operate within the company's traditional network of functional management. Getting the job done is the goal, and normal corporate constraints that help keep less experienced employees on the right track are relaxed when using tiger teams. The techniques these teams use to compress timelines are:  

 There is no waiting for senior management attention that can often take 30 days or more to occur in typical corporate environments.  

Start with firm draft of the final labeling.

 Everything works more efficiently if the project team starts with the end labeling in mind. Protocols are designed to address the desired label, data is analyzed to prove the defined labeling targets, and reports are written to support the draft labeling. Everyone from Marketing to Research & Development have the same goals for the product. 

 Work is done once because all the normal checkpoints, Clinical Quality Assurance (CQA), and Regulatory are involved in process during the origination, conduct, and completion of the operational activity. As team participants, the departmental Quality Control (QC), CQA, and Regulatory assure in-process quality and compliance. When the final work product or document emerges, sign-offs happen immediately. 

Team members retain accountability throughout the entire process.

 There is no multiple level of management sign-off, since the functional representatives on the project team are the departmental vice presidents and directors. If someone is accountable for writing a report and sends it to another team member, their accountability does not end once the next responsible person has received the report (i.e., "throwing it over the wall"). The writer remains accountable and is expected to follow-up and set the time for getting return feedback and completion of the activity. While responsibility can be delegated, accountability cannot. 

 Many activities are undertaken in parallel rather than waiting for serial results and everything that can be done in advance is done as early as possible. Advanced planning and prework are the keys to speed. Prework is completed and ready for integration when the final pieces become available. For instance, report shells can be written very early, practically at the same time the protocol is written. 

Feature Article

Using a template both accelerates a project's timeline and infuses it with best practices.

Drug Development on Rails: Part Two

On Wednesday, March 15, 2006, the media broadcasted that "two men were critically ill in a British hospital and four others serious in intensive care after suffering violent reactions to a new drug they took as part of a clinical trial." The Medicines and Healthcare Products Regulatory Agency (MHRA) announced that eight healthy men took part in the trial. Two of the men were given a placebo and six were given the drug. All six participants became seriously ill due to an adverse reaction to the drug. 

This was the Phase I of a clinical trial for a drug known as TGN 1412, which is a monoclonal antibody and was intended for rheumatoid arthritis and leukemia patients. Without any doubt, this Phase I clinical trial was conducted under the current regulations and undertook rigorous and comprehensive safety measures, with scrupulously designed procedures and carefully monitored processes. Nevertheless, this incident once again calls for an imminent need to improve the drug development process and should remind everyone of the crucial roles of "Critical Path" (CP) and "Roadmap" initiatives.  

In recent years, the Food and Drug Administration (FDA) through the Critical Path

  initiative and the National Institutes of Health (NIH) through the Roadmap

  initiatives have identified various technologies and discoveries to integrate into the therapeutic development process. The implementation of these initiatives can potentially improve the effectiveness and safety of therapeutics, and can also increase the efficiency of the clinical trial process by reducing the costs and time frames of trials.  

Scientific and technological evolution has spectacularly accelerated during the last quarter-century, causing an information explosion and breakthrough of discoveries. A vast amount of investment and research has been devoted to advanced technologies related to the health science field, which has led to new discoveries such as biomarkers, pharmacogenomics, gene therapies, cell therapies, and genomics. What is unfortunate, however, is that the application or integration of these technologies into the therapeutic development process has been very limited. Recently, CP and Roadmap initiatives have proposed several frameworks and platforms to facilitate the uptake of advanced technology into discovery methods and the clinical trial process. This way, valuable initiatives may optimize the introduction of more effective and safer novel therapeutics.   

Even though the CP and Roadmap initiatives have been proposed in recent years, they have generated a tremendous stimulation among researchers, clinicians, and scientists, as well as biomedical and biopharmaceutical industries. However, collaborative and harmonized efforts among government, academia, industry, and patient groups at the national and even international levels are fundamental components for pursuing the objectives of CP and Roadmap initiatives. In addition, the FDA and NIH have identified other  challenging frontiers that must be addressed prior to employing the CP and Roadmap.  

Furthermore, the relevance of these initiatives is not limited only to the stages of the medical product development process. These initiatives can also signify the continuous application of various technologies for a wide spectrum of postmarketing purposes, which is especially vital for health care delivery in the population level. In fact, there is growing attention to incorporating advanced technology into the "real world" and translating discoveries into clinical practice. Health care providers can utilize the "new therapeutic technology" for better patient care. These proposals have defined policies and frameworks that may also be extrapolated to the community-based clinical application of technologies for integrating molecular findings into a population. 

In conclusion, the implementation of the FDA CP and NIH Roadmap initiatives, which are currently emerging, will enlarge the capability of scientists, researchers, and clinicians to improve the safety and effectiveness of therapeutics and to deliver better health care to the patient population.  

 MD, MSc, St. Joseph's Healthcare, McMaster University

A Closing Thought

A discussion of the recent initiatives for applying advanced technologies in real world settings that have the capability to improve drug research, increase subject safety, and reduce development costs, which takes into account the collaborative efforts among government, academia, industry, and patient groups that are necessary to achieve these goals and translate new technological discoveries into clinical practice.

Research for the Real World

Leishmaniasis ranks third on the World Health Organization's (WHO) list of neglected diseases in terms of deaths per year. It is estimated that 350 million people are at risk. When untreated, death occurs within two years of infection. In the mid-1990s, physicians in Bihar, India, encountered antimonial resistant parasites and began looking for alternative treatments. At that time, miltefosine had been shown to have activity against leishmania in vitro and in animal models. Developing miltefosine for the treatment of visceral leishmaniasis (VL), or Kala Azar, was attractive, but the cost of clinical development would be high. Since the disease is primarily present in poorer communities in developing countries, a pharmaceutical company would find it difficult to make a return on investment on such a drug. However, one company was interested in partnering with other health-related organizations to bring miltefosine to market for the treatment of VL. 

In 1995, the Special Programme for Research and Training in Tropical Diseases (TDR) agreed to collaborate with Asta Medica (now known as Zentaris), the company that originally discovered the drug, in the development of miltefosine for VL.  The compound was assessed and incorporated into TDR's development portfolio. In 1998, in collaboration with scientists in India, the government of India (Indian Council for Medical Research, ICMR), and the private sector (Asta Medica), TDR initiated a Phase II clinical trial of miltefosine for VL in Bihar, India. 

TDR shared the cost with the company for the clinical development of miltefosine. A memorandum of understanding (MOU) was drawn up between TDR and Asta Medica (Zentaris) to ensure the availability and affordability of the drug in endemic countries if it proved to be safe and effective. A public–private partnership model was developed for this project. The model involved substantial participation of the Indian investigators as well as ICMR and the Indian Kala Azar control program. As the project neared the culmination of the Phase III clinical trial, the involvement of the Indian Kala Azar control program increased. 

After drug registration in India, ICMR took the leadership role in organizing the Phase IV study in India and Nepal. TDR played a supporting role, mainly involved with capacity building at the study sites and setting up central laboratories to support the Phase IV study. Once the Phase IV study was completed, TDR's leadership role in the project was transferred to WHO's Southeast Asia Regional Office (SEARO). SEARO had the advantage of closer regional ties with control programs in disease endemic Nepal, Bangladesh, and India. 

To start the project, TDR set up a product development team (PDT), a small team of experts from India, Europe, and the United States. The role of the PDT was to direct the development strategies and oversee the progress of the study. According to already established TDR policy, all clinical studies receiving TDR support must be carried out according to international best practices standards, including Good Laboratory Practice (GLP), Good Clinical Practice (GCP)

  and—more recently—Good Ethical Review Practice.

Although these requirements are easily said, adherence is less easy, particularly by large governmental agencies. 

Ready for the pivotal clinical trial in adult patients, all investigators were trained in the principles of GCP, the ethics of clinical research, and all the procedures required by the protocol. TDR required that the investigators demonstrate an understanding of GCP as well as a practical capacity to implement GCP in terms of the protocol. Adherence to international GCP standards and the Declaration of Helsinki

  (World Medical Association, 1964) were crucial since the objective of the project was to register the drug for treatment of VL. 

The introduction of strict GCP proved challenging for the investigators. It involved a new system and a new working environment. All personnel involved in the trial were trained for their roles and responsibilities. The principle investigator of each trial site needed to understand that he/she had overall responsibility for all activities at the study site. Much of the paperwork involved was felt at first by the investigators to be unnecessary and bothersome for day-to-day work in the clinic. Through training and practical experiences with the new system, investigators relaxed and adapted to working according to GCP principles. 

As part of the effort to comply with GCP guidelines, TDR introduced clinical trial monitors into the study. Clinical trial monitors played a crucial role in the study, providing oversight and direction during the conduct of the research. TDR clinical trial monitors are physicians and scientists trained in research and GCP prior to joining the team. Before participating in the trial, they were trained on the specific protocol, including all the procedures and requirements of the protocol, so that they could assist the investigator in solving the problems that occurred at the study sites. They also assisted the investigators in setting up standard operating procedures (SOPs) for the conduct of the study to ensure the smooth running of activities at the study sites. They reviewed and verified the data to ensure both the existence and quality of the source data. They provided additional assurance to TDR that the study was in compliance with GCP requirements. 

The clinical monitors visited the study sites monthly to validate compliance with GCP. Routine audits were performed at all study sites. These helped TDR to ensure that the data generated at the clinical trial sites were of adequate quality. Should the drug then prove to be safe (well tolerated) and effective, it could be registered in India and elsewhere, including Germany, where the sponsor company is situated. 

The laboratory that supported the clinical trial was trained in the principles of GLP. Quality control and assurance were implemented in this laboratory. The readings of the parasite slides were very important for the study, as these readings provided the parameter by which efficacy was evaluated. The accuracy of the reading was crucial. TDR, in collaboration with Zentaris, arranged for 10% of the parasite slides to be read at the end of the trial by an independent expert designated by the ICMR. When there were discrepancies between the readings, face-to-face meetings were arranged between the independent expert and the laboratory to discuss and resolve the discrepancies. This arrangement contributed to the overall capacity building of the laboratory. 

The Phase II and III clinical studies in adult patients were performed entirely in private clinics. This may not be sustainable in the long run. TDR felt that more capacity building needed to be done in terms of sustainability of clinical research in this region of India. It was clear that ICMR's Kala Azar research institution in Patna (RMRI) was an ideal place to achieve this. 

TDR sent a team to assess RMRI's capacity as a GCP clinical trial site. The team identified several areas that needed to be improved, including its laboratory, the capacity and motivation of the staff for doing research, and its ethical review system. TDR had a discussion with the Director General of ICMR, Professor N.K. Ganguly, on the collaborative efforts needed to bring the quality of research done in this institution to international levels of good research practice. ICMR agreed to provide funding to support the improved infrastructures identified by TDR, which was responsible for assisting the institution in team building and technology transfer. 

TDR funded the director of RMRI, Dr. Sujit Bhattacharya, to visit a research institution in Bangkok, Thailand, and participate in a course on ethical review in biomedical research. Upon his return, Dr. Bhattacharya revised his ethics committee function by implementing WHO Operational guidelines for ethics committees that review biomedical research. 

A series of workshops for laboratory staff was held on writing SOPs. After the renovation of the institution and the retraining of all staff, the TDR team went back to the site to make another assessment. It appeared that the staff had become more motivated, the RMRI–ICMR research institution in Patna was revived, and the site was ready to perform clinical trials compliant with GCP. As a result of these efforts, RMRI was selected in 2001 as one of the study sites for carrying out the miltefosine pivotal trial for pediatric patients. 

Even after the registration of miltefosine in India in early 2003, the Indian control program was concerned about patient compliance with the treatment regiment in the field. The treatment course requires 28 days to achieve reliable efficacy. The challenge was to ensure a method for outpatient compliance. All of the clinical studies so far, in both adults and children, involved only in-patient care. Thus, patient compliance to the treatment regiment was easier to control and verify. 

The control program requested that the Phase IV study be carried out to answer the compliance issue and to gain more safety data before using the drug in a control program, where less supervision would be available. At this time, RMRI in Patna had enough confidence to lead the Phase IV study. 

ICMR provided funding for the study, and requested that TDR assist RMRI with the assessment of study sites, the training of investigators, the increase of local laboratory capacities to support a Phase IV trial, and the provision of clinical trial monitors for the study. Zentaris was asked to support RMRI with the data management. Under the leadership of the RMRI team, more than 20 private clinics in Bihar were screened as possible sites for a Phase IV study, of which 15 were selected. More than 10 labs were assessed and five were selected to participate in the trial. Six months after the initiation of the study in Bihar, one additional site in Nepal was included. 

After site selection, RMRI arranged investigator meetings to discuss the Phase IV protocol and GCP training for all investigators. GLP training was done in parallel with the GCP training. All training was done at RMRI under the leadership of RMRI staff and with assistance from TDR. 

The integration of GCP into existing practice in private clinics proved to be a daunting task. It demanded considerable interaction between RMRI and the centers, as well as coordination between the laboratories and the clinics. The trial was monitored by the TDR clinical trial monitoring team. 

TDR asked that a laboratory team from Bangkok, led by Professor Kesara Na-Bangchang, assist RMRI in setting up several laboratories for the Phase IV work in order to improve operations under field conditions. The selected laboratories were trained in GLP. The methodologies in the laboratory required by the study were harmonized across the five laboratories. A workshop on writing SOPs took place at RMRI; to ensure the integration of the SOP into actual practice, a follow-up was performed at each laboratory by a team from RMRI and Bangkok at both one-and three-month intervals after the initial training. 

Every laboratory worked according to the same standard operating procedures, with the exception of a few modifications based on the different needs of the laboratories—but always in compliance with the protocol. The monitoring of the quality of the laboratory performance was assessed at intervals by the TDR clinical trial monitors. 

The Phase IV study was completed with satisfactory results. The results were presented to the Bangladesh, Indian, and Nepal national control programs at a meeting organized by SEARO in December 2004. RMRI now has the capacity not only to carry out GCP clinical trials, but also to coordinate GCP trials in areas with difficult environments and limited medical resources. 

Having been informed about the design, capacity-building initiatives, and progress in the development of the miltefosine project, SEARO initiated the Kala Azar elimination program with the aim of eliminating Kala Azar from the Indian subcontinent by the year 2015.

  The program involves the full engagement of the control programs of the three countries, Bangladesh, India, and Nepal. The program is now considering miltefosine for its first-line drug treatment. 

The development of miltefosine served both missions of TDR: to develop new tools for neglected infectious diseases and to build research capacity in disease endemic countries. Good collaboration between the private and public sectors along with smooth transference of leadership at each stage of development were important milestones throughout the project. 

The goal of TDR, when engaged in the development of miltefosine, was to have an oral drug that is effective, well tolerated by patients, accepted by the communities, and integrated into the control programs of the disease-endemic countries. The capacity building that was part of the development process, which lead to data of good quality, ensured human subject protection and provided a strong basis for the registration of the drug in both India and Germany. Beyond drug registration, the development model described here also lead to national implementation programs for disease control and eventual elimination according to a model of drug availability and affordability in resource-poor settings. 

The experience from this project suggests that early involvement of local researchers, local research institutions, and the local government (the control program) can create a smooth interface between research and implementation. Beyond this, there is a direct impact on public health in the region as well as an increased capacity for the region to address more directly its own health challenges in the future. 

The authors wish to express their appreciation to Francis P. Crawley of the Good Clinical Practice Alliance—Europe and Professor Win Gutteridge, TDR Consultant, for their critical remarks during the drafting of this article. 

 is clinical coordinator with the Special Programme for Research and Training in Tropical Diseases (TDR), The World Health Organization, 20 Avenue Appie, CH-1211 Geneva, Switzerland, email: karbwangj@who.int. 

 is with the Indian Council of Medical Research, Ansari Nagar, New Delhi 110029, India.

1. International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH), 1996. Note for Guidance on Good Clinical Practice. 1 May 1996 (http://

2. World Health Organization (WHO), Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products. Annex 3 of The Use of Essential Drugs. Sixth Report of the WHO Expert Committee. Geneva: World Health Organization, 1995, 97–137. 

3. World Health Organization (TDR/WHO), Operational Guidelines for Ethics Committees that Review Biomedical Research. Geneva: WHO, 2000 (http://

www.who.int/tdr/publications/publications/ethics.htm

4. World Medical Association, 1964. Declaration of Helsinki: Ethical Principles for Research Involving Human Subjects. Adopted by the 18th World Medical Assembly, Helsinki, Finland, June 1964. Amended by the 29th World Medical Assembly, Tokyo, Japan, October 1975; the 35th World Medical Assembly, Venice, Italy, October 1983; the 41st World Medical Assembly, Hong Kong, September 1989; the 48th General Assembly, Somerset West, Republic of South Africa, October 1996; the 52nd General Assembly, Edinburgh, Scotland, October 2000; Washington 2002; and Tokyo 2004 (http://

5. World Health Organization, Elimination of Visceral Leishmaniasis: Report of an Intercountry Informal Consultative Meeting, Varanasi, India; 10–14 November 2003. WHO Regional Office for Southeast Asia, 2004, SEA-VBC-84. 

*To whom all correspondence should be addressed.

A collaborative model for increasing drug availability in resource-poor, disease-endemic countries

Building Research Capacity into Drug Development

Software provides complete visibility into the regulatory submission process

(Wayne, PA) recently announced an update to its enterprise submission process management solution. Viewpoint 3.6 streamlines the regulatory submission process by affording visibility into the planning and management of the drug submission process and allows users to track, manage, and compile any type of regulatory application.  

Viewpoint 3.6 Resource Estimator, Reviewer, and Regulatory Dashboard have been upgraded to provide enhanced workflow estimation, collaboration, and project tracking across the submission life cycle. The new Web-based Reviewer allows content contributors to view and validate their documents in the context of a submission. This, Octagon says, lessens the possibility that clinical trial professionals will miss a submission date or file an incomplete or noncompliant eCTD submission. 

Octagon Research Solutions, (610) 535-6500, 

eShowcase

eShowcase: ViewPoint 3.6

Wireless technology takes the worry out of inaccurate patient reported outcomes 

 (Charlestown, MA) has created a new device that employs wireless technology to measure physiological measurements such as peak expiratory flow or blood sugar levels wirelessly, then integrates the data with an eDiary. The technology also enables subjects to send subjective data such as pain level versus activity level. With eSense, they can wear a small device to record data during the day, then return home and transmit the information to an eDiary that night. The advantage, says PHT, is that clinical trial subjects no longer have to remember scores or times, or worry about transcription errors. 

The technology that makes eSense possible is a low-power wireless design that allows devices within 10 feet of each other to communicate. This also enables eSense to be integrated into tiny, wearable devices that are more convenient. Subjects simply use the device near their eDiary and the data transmits automatically, with date and time stamps for every reading.  

eShowcase: PHT eSense Sensors

Although the major drug development regions of the world are recognized to be North America, Europe, and Japan, continuing growth of the pharmaceutical market in emerging regions is being accompanied by similar growth in clinical trial activity outside the traditional "big three" markets, as reflected in recent editions of 

 where feature articles have included overviews of Africa and Asia. Australia might be considered as laying somewhere in between: Australia's market size certainly does not compare to the big three pharma superpowers; nor can it be considered as an emerging market. Major Australian cities regularly rate highly on quality of life surveys, but it may surprise some that a recent international benchmarking study undertaken by 

) identified Australia as the number one location to conduct pharmaceutical clinical trials. 

 Intelligence Unit study, "Benchmarking Study of the Australian and International Pharmaceuticals Industries," was commissioned by the Australian Government Department of Industry, Tourism and Resources; Invest Australia; and the Victorian Government Department of Innovation, Industry and Regional Development.

  It compared and benchmarked Australia against the United States, the United Kingdom, Germany, Japan, Singapore, and India across a range of indicators including clinical trials, the intellectual property system, the regulatory environment, and the investment and business environment. Australia ranked second overall, with Singapore ranking first. Australia scored highly for many indicators relating to the industry skills pool, practices, and regulatory processes, but scored below Singapore and India on costs. In relation to clinical trials, Australia ranked first overall (as a weighted aggregate), boosted by low average costs of clinical trials, a relatively large amount of recognized trial sites, and a high percentage of clinical trials completed within the allocated time. Of particular interest to overseas sponsors was the observation that Australia does less well on the total amount of clinical trials taking place even on a per-capita basis, suggesting there is capacity for further growth within the sector. 

While being identified as an attractive location for conducting clinical trials is music to the ears of the Australian pharmaceutical and biotechnology industry—an AUD$12 billion sector employing 35,000 people, exporting almost AUD$2 billion a year,

  and the second largest contributor of manufactured goods to the Australian economy (more than its wine industry)—potential clinical trial sponsors are perhaps more concerned with the realities. They might ask the following: Will my intellectual property be protected? How do I obtain regulatory approval? How long will it take? How fast can I enroll patients? How do I get my clinical trial material into Australia? Will the study be performed according to ICH GCP? Will the FDA or the EMEA recognize the quality of the study and accept the data? 

Perhaps reflecting its historical and constitutional links with Great Britain, Australia's regulatory framework for therapeutic goods is primarily based on that of the European Union. Periodically, the Australian Therapeutic Goods Administration (TGA) reviews regulatory guidelines issued by the European Community (EC) and issues statements on whether a specific EC guideline has been endorsed or not. In the case of particularly innovative, controversial or evolving regulatory matters, the TGA tends to take a best practice approach, whereby it considers existing overseas guidelines, particularly those issued by the ICH, EC, and FDA, in the context of the local Australian industry, health care, and social factors.   

A good example of this best practice approach is the TGA and the National Health and Medical Research Council (NHMRC) jointly established Review of the Australian Arrangements for Clinical Trials & Access to Unapproved Therapeutic Goods (referred hereafter as "the Review") that was commissioned in April 2003, and the report published in February 2005.

  The motivation for commissioning this Review was multifaceted, including: 1) the EU Clinical Trial Directive 2001/20/EC; 2) the goals of ensuring the timely access to safe and efficacious new therapies for the public, public safety, and that the Australian pharmaceutical industry remains internationally competitive; and 3) the expected formation of the joint Australian and New Zealand Trans Tasman Regulatory Agency in the second half of 2007. 

CTs in Australia: Schemes, Locations, Phases  			

Public submissions in response to the Review's report closed on 8 July 2005 and are under consideration. The response of the Australian authorities to the Review's recommendations and the public submissions is expected in the second half of 2006, but most anticipate that the EU Clinical Trial Directive 2001/20/EC will not be fully endorsed and that the existing regulatory framework for clinical trials in Australia, the Clinical Trial Exception (CTX) and Clinical Trial Notification (CTN) schemes (see sidebar, "Regulation of Clinical Trials: Comparing the CTN and CTX Schemes"), will continue albeit with some tweaks here and there—such as additional support for the institutional ethics committees (IECs), especially in the context of advanced and high-technology investigational products where the TGA is likely to coordinate the drafting of additional guidance documents to assist the EC, and the EC is likely to have access to a committee of national experts for use on a case-by-case basis. Although these additional measures may in some cases cause delays in the CTN process, this is counterbalanced by the fact that they are also likely to reduce the need for the EC to refer such clinical trials to the TGA (via the CTX process). 

Regulation of Clinical Trials: Comparing the CTN and CTX Schemes			

It is important to note that clinical trials involving gene therapy or related therapies require approval from both the IEC and the Gene and Related Therapies Research Advisory Panel (GTRAP), an expert committee established by the NHMRC. 

Because it is an island, Australia is quite protective of its borders. Typically, a specific import permit is not required for clinical trial material, however some clinical trial materials may be subject to additional restrictions and separate approvals may be required (for example, products containing substances that are listed as prohibited imports, and materials of biological origin). 

As highlighted in the Review, there is a lack of publicly available data on the nature and number of clinical studies conducted in Australia, especially in recent years. Data taken from 1990 to 2000 presented in Figure 1(a) demonstrate that the far majority of clinical trials are conducted under the CTN scheme. The Review also indicates that during the 1990s the majority of clinical trial sites were in Victoria and New South Wales [see Figure 1(b)], the Australian States with the greatest population, and the far majority of studies were Phase III [see Figure 1(c)]. Although the data presented in Figure 1 is several years old, there is little reason to expect that the predominant locations of the clinical trial sites have changed significantly, despite increasing activity in the biotech industries within Western Australia and Queensland. Similarly, one would not expect the proportion of the study type performed to have changed dramatically, although if the Review's recommendations are endorsed by the Australian authorities the comparative simplicity of the CTN scheme in comparison to the FDA investigational new drug application (IND) or EU clinical trial application (CTA) procedures might become increasingly attractive to time-and money-sensitive sponsors eager to generate early proof-of-principle clinical trial data. 

Australia has a strong reputation for the quality of its scientific and medical research. In relation to Good Clinical Practice, the TGA has adopted the European Guideline CPMP/ICH/135/95 (and therefore the ICH E6 guidance) in principle, with some elements modified according to local regulatory requirements. Adherence to ICH GCP is, under Regulation 12AB of the Therapeutic Goods Regulations 1990, mandatory in Australia for trials conducted under CTN or CTX. 

As highlighted in the sidebar "CTs in Australia: Pros and  Cons," the regulatory framework for clinical trials in Australia, which is internationally recognized for its science and highly trained workforce and has an intellectual property regime that compares favorably to the European Union and the United States, is quite attractive for overseas sponsors. Moreover, Australia appears to deliver in terms of ICH GCP standard clinical trials performed in a timely and cost effective manner (due to the spending power of the U.S. dollar and the Euro in Australia, and the relative lower cost of medical procedures and investigator fees). Nevertheless, the total number of studies conducted is relatively small in comparison to the EU or the United States. The reasons for this are multifactorial, including the modest size of the local industry and  the local pharmaceutical market. Furthermore, despite a relatively multicultural society, especially on the East coast, the relative size of the potential trial subject pool is modest and perhaps counterbalances the time and cost efficiencies that Australia can offer in terms of trial approval and conduct, particularly for larger trials. An additional complication for overseas drug developers is the need for a local commercial sponsor for an Australian study (not all local CROs are willing to fulfil this role), and the fact that organizing local insurance for the study can often be problematic (due to the relative lack of local insurance brokers and the relatively high level of insurance that might be required). Of course geographical distance and time differences also must be considered, although with strong project management the time differences can be exploited by increasing the overall working day for a particular project. 

The pros and cons of conducting clinical trials in Australia were highlighted at the AusBiotech 2005 National Biotechnology Conference and Business Partnering and Investment Forum that was held in Perth from 20–23 November. During the open-panel forum at the conclusion of the Clinical Trials session, the different perspectives of the delegates were highlighted: the local CROs quite rightly and passionately pointed to the pros, including those listed in the sidebar. Many of those delegates employed within the Australia subsidiaries of big pharma, however, pointed out the cons that they find difficult to overcome when trying to convince their EU-or U.S.-based head office that Australia should be considered in the planning of a specific clinical trial program. 

The AusBiotech 2005 session highlighted very well the realities of clinical trials in Australia. European Union- and U.S.-based drug developers must focus their development activities in those regions, and it is no doubt preferred by the regulators in those regions. However, in certain circumstances Australia is an attractive option. As discussed earlier, in many cases early phase or proof-of-concept studies can be conducted without the burden of an EU CTA or U.S. IND, a significant advantage in these extremely competitive times.  With the data generated to ICH GCP standards and subject to stringent IP regimes, it can be used to add substance to fundraising or partnership activities and to support future clinical trial applications in the EU and United States. For later stage development, given their quality and cost-effectiveness, Australian sites in an international multiple-site clinical trial program can add value, especially in indications that have a high prevalence rate in Australia (such as melanoma or asthma) or that are seasonal (such as rhinitis). Comparative Phase III data generated in Australia is also of significant value for local pricing and reimbursement activities. Of course with strong project management there is also the possibility of taking some time to soak in the sun—just remember to pack the sunscreen and a good hat! 

 PhD, is with Voisin Consulting Australia Pty Ltd, Milton House, 25 Flinders Lane, Level 1, Melbourne, VIC 3000, Australia, +613 9663 9008, fax +613 9663 9009, email: 

Favorable cost, research quality, and timeline measures are attractive to overseas sponsors.

Applied Clinical Trials-09-01-2006

The EDC Decision

Training in Pediatric Research

Spotting the "New" Managed Site Networks

Drug Development on Rails: Part Two

Research for the Real World

Building Research Capacity into Drug Development

eShowcase: ViewPoint 3.6

eShowcase: PHT eSense Sensors

Australia: The Number One Place for Clinical Trials?

New Research Models Spur Third-World Efforts

eShowcase: TrialSpace Designer

Call for Comments on Viral Safety Guideline

Saving Lives