As other industries race to take advantage of offshore opportunities, pharma has been more reticent. In April 2006, according to 

, pharma companies were performing 838 ongoing trials in the United States and 158 in the UK. At the same time, however, companies reported just 81 trials in Russia, 49 in India, and 31 in China. That should change soon. The prediction is that pharma companies will double their clinical research activities in developing nations over the next three years. 

Nevertheless, when senior pharmaceutical executives discuss offshoring, an unsettling trend emerges: In making offshore decisions, they often rely on anecdotal and incomplete information rather than systematically benchmarking cost, demographics, regulations, and infrastructure. It's time for a new approach. 

An index that provides a data-driven analysis of the evolving clinical trials landscape, and indicates where the best opportunities exist, helps companies make offshore decisions. The Country Attractiveness Index for Clinical Trials (created by A.T. Kearney) provides a fact-based ranking of low-cost countries, grading the attractiveness of 15 offshore locations by evaluating five key areas: patient availability, cost efficiency, relevant expertise, regulatory conditions and national infrastructure. (See "Methodology of the Study") The United States', UK's, and Germany's clinical trial use were used as benchmarks to predict the viability of doing trials in emerging countries. 

According to the Index, China, India and Russia emerged as the most favorable destinations. (See "States of Attraction", for a snapshot of offshore destinations.) 

The opportunities in lower-cost countries are simply too large to ignore. For example, depending on location, clinical trials in lower-cost countries cost 30 to 65 percent as much as trials in the United States or Western Europe. The revenue implications are equally attractive. According to the index, in low-cost countries, Phase III clinical trials can be completed up to six or seven months sooner than in domestic markets. This translates into getting the drug to the market faster, thus providing earlier relief to patients, a faster return on investment for the company, and longer patent protection. 

However, before moving into a developing country, there are important questions to answer. Which countries are most "open" to pharmaceutical companies? What makes one low-cost country better than another? How do countries compare in infrastructure? Which has the best patient pool? Better regulatory conditions? Intellectual property protection? 

Many pharmaceutical companies have settled for

answers to these questions, often relying on existing relationships they have in a country. The reason for this approach is understandable—there is just not enough good information available on developing countries to allow executives to make sound offshore decisions. Pharma companies need a barometer of success to determine which foreign countries would provide the best opportunities for their clinical trials. 

China is among the most attractive markets for Phase III clinical trials. With the world's largest urban population, the country provides a vast patient pool and a large infrastructure of hospitals. China also has close to 1.4 million doctors and more than a million nurses and technicians. Their low salaries, in part, mean that conducting a trial in China could cost about half of what it would cost in the United States.  

China's appeal is not lost on pharmaceutical companies—with some estimates suggesting that the country could overtake the United States as the world's largest market by 2020. AstraZeneca was among the first to enter China for R&D, opening its East Asia Clinical Trial Center in Shanghai in 2003. But other companies have been slow to follow.  

One reason for their delay is that bureaucracy and strict government regulations pose ongoing risks for companies. For example, it can take nine to 12 months to get a trial approved by the Chinese State Food and Drug Administration (SFDA). Companies must obtain a drug import license for every shipment that enters the country, rather than one for each type of drug. China only sporadically enforces intellectual property rights, and cultural and language differences are costly due to the need for translation services. 

Evaluation of Study In the index analysis, categories were weighted according to the relative importance each plays in location decisions.  			

The Chinese government is making changes to attract more foreign-sponsored clinical trials. For example, the government has passed new regulations and is establishing clinical practice centers to train investigators and staff. Although only hospitals designated by SFDA can conduct trials, principal investigators from these institutions often have extensive experience with Western companies, making for a smoother process.  

Much like China, India offers a vast population and a growing market. The capabilities and expertise of the country's scientists are on par with the highest international standards, and clinical trial data from India frequently are accepted at major conferences and by prestigious journals. With English as the primary language for education and research, companies in India can have seamless working relationships with US companies, and strong overall economic growth is bound to lead to improvements in the healthcare infrastructure. 

The Indian government is aware of its burgeoning position in the industry and is offering incentives to promote local pharmaceutical companies and attract foreign firms. For example, companies that conduct in-house R&D receive a tax exemption on all profits. Within the next two years, India plans to create an independent drug regulatory authority similar to FDA. This central group should lead to more rigorous and consistent drug regulations and higher overall standards. Eventually, India hopes to establish a reciprocal agreement with the United States so when one country approves a drug, the other will clear it at the same time.  

The incentives have coaxed more than one company to India: GlaxoSmithKline conducted several trials in 2004 and Pfizer doubled its clinical research investment in India to roughly $13 million, with plans to invest another $30 million over the next five years. This may be a tiny fraction of Pfizer's total global R&D of $8 billion, but the interest indicates a growing optimism for this market. 

On the downside, intellectual property (IP) protection in India has been weak and the country currently does not permit foreign companies to conduct Phase I clinical trials—though both factors are likely to change in the near future. There are some bureaucratic headaches as well: Pharma companies are required to coordinate their efforts with local physicians and hospitals and to perform toxicology tests between Phases II and III, which can cause a delay of six months. 

Pharmaceutical companies report performing 81 trials in Russia, though this number is likely to increase as more companies recognize the benefits of working in Russia. In addition to lower costs, the country offers an appealing patient pool, and under the centralized medical system, patients with similar symptoms receive treatment in the same ward, which facilitates patient recruitment. Many of these patients also are treatment-naïve, meaning they haven't been on prior drug therapies. Such factors allow companies to recruit patients up to 10 times faster than in the United States—slashing the time and money required for a clinical trial. 

The inherent problems in Russia are similar to those in India and China. IP protection is weak, and the government creates a variety of hurdles—including a tax on clinical trials. One major concern is the ethics of patient recruitment. Since doctors can make ten times their salary by performing clinical trials, there is an underlying fear that some doctors may neglect to inform patients of important risk factors. Companies performing trials in Russia should establish clear procedures and keep a close watch on patient recruitment to ensure compliance with international ethical standards.  

Knowing where to move is just the first step in the offshore decision-making process. The next step is determining how to move offshore, which includes managing the inherent risk of doing business in a less developed country. Companies should begin slowly by conducting a small trial or one component of a trial to test whether the fit is right. This will help reduce risk and allow executives time to find out what works and what doesn't. In general, it will take two or three trials in a new location to develop a solid base offshore. To further mitigate risk, many companies collaborate with a multinational clinical research organization (CRO) with hands-on, in-country experience.  

Over the longer term, companies should develop a comprehensive strategy that pinpoints and manages ongoing risk. The following should be key aspects of the strategy: 

 Legislation to protect intellectual property varies widely from country to country, as does enforcement. Until 2005, for example, India granted patents only on process, not product, leaving the door open for local companies to reverse engineer drugs in a way that would infringe on US patent laws. Today, many developing countries—including India—are strengthening their patent laws, partly because they want to attract western companies. Although the shift is encouraging, skepticism no doubt will linger until new legislation is fully tested and enforced. In the meantime, companies must not underestimate the importance of due diligence and tight contracts.  

 Because clinical trials vary from one treatment to another, FDA has not established blanket rules governing them. Instead, it relies on companies to conduct clinical trials that adhere to their own highest standards—and periodically requires companies to open up their international sites for inspection. And FDA has good reasons—in 2004, it found that researchers failed to follow protocols in 30 percent of the inspected sites.  

An increasing number of countries, however, are improving their standards for trials. In addition to FDA guidelines, the international Good Clinical Practice (GCP), provides a common platform that all pharmaceutical companies, local professionals, and CROs should follow.  

Learn the culture and understand ethnic differences.

 Differences in how professionals practice medicine may skew trial results or affect trial execution. Local customs also may undermine results. In China, for example, herbal medicines account for up to one-third of the nation's pharmaceutical sales. Researchers may not report the use of traditional herbal medicines, but they could affect the results.  

Ethnic differences may also include factors that could affect trial results, such as genetic variations. Companies should design clinical trials to recognize ethnic diversity, and they should ensure that a sufficient percentage of trials take place in other regions—a practice that is also useful in meeting FDA's requirements for ethnic diversity. Knowledge of ethnic diversity will be an asset if long-term plans include selling within clinical-trial countries.  

As companies explore offshoring, they should first review their own decision-making processes and metrics. Is there a process for assessing the supply market? Are the evaluation criteria comprehensive and objective? It is important to address all supply-chain implications and other company-specific goals early in the process, and to monitor all aspects of the deal, especially those that might affect location attractiveness. With this level of rigor, companies are more likely to realize all the benefits of offshoring clinical trials to low-cost countries. 

Marjorie Speers is the executive director of the Association for the Accreditation of Human Research Protection Program (AAHRPP), which is dedicated to raising the standard of human protection in research. She also oversaw the 2001 report "Ethical and Policy Issues in Research Involving Human Participants," commissioned by President Clinton's National Bioethics Advisory. Speers recently spoke to PharmExec about the necessity to protect individuals' rights in overseas clinical-trials recruitment, and about the economic implications and the ethics of offshoring. 

PharmExec: A recent report indicated nearly 40 percent of clinical trials are conducted in poorer countries, such as Russia and India, where costs are lower and patients more vulnerable—up from about 10 percent in 1999. What kinds of questions of ethics and oversight does this raise?

 There are multiple ethical challenges in conducting research, especially when the costs of material, labor, and intellectual property are dramatically different between developed and underdeveloped countries. In large part, the ethical and oversight criteria are the same, but groups charged with protecting the welfare of human research participants—ethics committees or institutional review boards (IRB)—always become concerned because there is a potential for individuals to be recruited inappropriately. This is particularly critical when recruiters target participants who are vulnerable to coercion or undue influence. 

If the research is paid for by US federal funds, or if the data from the foreign studies will be used in support of licensing in the United States, then the IRB must review and approve the research according to the same or similar criteria that apply in the United States. Once the research is reviewed, it has to be conducted in compliance with US standards, which includes obtaining and documenting informed consent. Among the ethical conflicts that can arise is cultural and societal differences that influence how we communicate, obtain, and document informed consent from individuals who have a different perception of autonomy than those from Western countries. 

Do you agree that the shift of drug testing to poorer countries is largely being driven by economics?

Economics, for the most part, is driving the exportation of clinical trials out of the United States. Costs of conducting trials are much less in other countries; labor and supply costs are less. The added attraction of many developing countries is the large populations from which subjects can be recruited. Many of the prospective participants have never been exposed to treatments, making them attractive candidates to be studied. 

At least one other motivator for conducting research outside of the United States is the lack of federal or national regulations to protect human subjects. While many countries have adopted good clinical practice guidelines, others do not have any code of ethics that carries the force of law. And even though the same ethical standards apply throughout the world, the practice of the standards is only as good as the enforcement of the international guidelines or US regulations. 

By doing offshore clinical trials, do researchers exploit the vulnerability of foreign patients who are eager to sign up because they lack viable alternatives?

This is a difficult question because one can argue on both sides. Some say that conducting clinical trials with vulnerable patients is exploitive because they cannot make a truly voluntary decision to participate in the trial. Others argue that it isn't exploitive because these individuals know what they are doing and get better healthcare access. It becomes clear that the sponsors, IRBs, and the investigators have an obligation to make certain that the trial is well-designed, and that there is a balanced system of maximizing benefits and minimizing risks. 

What are the implications when a clinical trial is done in a foreign country, especially in a Third World country, but the manufacturer then tries to get approval in the United States where the conditions are clearly different? 

The standards for conducting clinical trials are becoming more and more global. Sponsors have worldwide operations and when they conduct trials, they often plan on submitting the results to more than one country for approval. The sponsor makes a decision about where the results will be submitted before conducting the trial. If the results will be submitted to FDA, then the trial must be conducted in accordance with US regulations and practices—even in a foreign country. In developing countries, researchers face many challenges, but the ethical standards embodied in the US federal regulations must be followed. For example, illiteracy rates are higher in developing countries, so the researchers are required to choose language that explains the trial carefully. 

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In general, it will take two or three trials in a new location to develop a solid base offshore.

Fishing for Opportunities

Enormous interest and rapid uptake has spurred electronic data capture (EDC) within the pharma industry. And why not? EDC has made it fundamentally easier to manage clinical data and, in the process, complete trials. 

Most companies have bought into the idea that EDC is a logistical replacement for paper-based recording of clinical data. But the industry, for the most part, has yet to take advantage of the qualitative advantages of collecting data in an electronic format. These EDC "sweet spots"—which include data capture beyond letters and numbers, data analysis, and study management—can be seen in studies across many therapeutic areas, but have particular application in complex disease areas. Paper-based methods are not inadequate, but are more prone to error, inefficiency, and delayed access to data, and can affect study management and even the outcome. 

By its very name, it's obvious that the core function of EDC systems is data capture. However, EDC effectively expands the scope and type of data that investigators can capture easily. This has particular utility in several specialty areas.  

Clinical testing for oncology drugs often involves tracking very sick patients within clinical trials who must take multiple medications. Because of the number of medications and the frequency of change, the management of concomitant medication data presents one of the most difficult challenges for companies; investigators often find it hard to track the start and stop dates of individual medications. EDC systems categorize and display these measurements easily. 

These systems also minimize queries by automating the coding of medications—Advil, Motrin, and ibuprofen are all the same medication, but for accurate analysis it is essential that they are referenced the same way. EDC systems also can track a variety of indicator lesions for solid tumors, and issue automatic queries if any indicator lesions are not recorded in subsequent visits. 

Researchers often find it best to capture observations in opthalmology trials with specific drawing tools that allow investigators to show the nuances of specific lesions or visual defects. They use the tools to take actual notes on the elecronic diagram or make changes to drawings. Modern EDC systems can capture these images, and supplement them with text narrative, to provide a fuller and more accurate description of a variety of eye pathologies.  

  These clinical trials are highly complex and usually require rating scales to measure and benchmark the effectiveness of the drugs that are under study. These scales can be somewhat subjective and can be difficult to use consistently between evaluators, but they can combine crucial data with clinical findings (i.e. the use of MRIs with clinical observations for MS studies.) 

Diseases of the skin are usually visually apparent, and clinical trials that study dermatology conditions benefit from capturing photographic images of the affected skin. Here, EDC systems capture and catalog images in the study, which can augment the narrative and assist with analysis, review, and publication of study results. Although advanced image analysis is currently beyond the scope of most clinical studies because it is only cost effective at large volumes, EDC can help it become a more crucial element in the future. 

The capture of radiographic, MRI, and PET scanning data—or binary displays such as ECGs and Pulmonary Function tracings—can help companies more fully capture the data available to them. Finally, esoteric laboratory data are frequently generated in university settings on platforms that have no password controls and no audit trail associated with them. In other words, they are not compliant with 21 CRF Part 11, a regulation that allows electronic records and signatures to be as valid as paper records and handwritten signatures. Using an EDC system, these can be captured in a 21 CRF Part 11-compliant manner.  

EDC also offers several advantages to companies that use it to analyze the data they collect during clinical trials.  

In part, that's because EDC offers a safety net against errors. EDC  has built-in edit checks, so there are fewer errors that can creep into the database. Given that the cost of correcting a single error starts at about $150—depending on when during the trial it is caught and corrected—this can result in significant savings.  

Additionally, an EDC system can increase the efficiency of data coding, provided that the system is coupled with an auto-encoder and the auto-encoder is updated with sponsor dictionaries throughout the study. Statistical transformation and interpretation of data is easier when the system can perform data exports to common pharma industry platforms.  

Beyond facilitating the statistical analysis of clean datasets, a quality EDC system also can help sponsors share and interpret clinical data with partners or key investigators. These technologies allow data interpretation to be done collectively or in an online forum where discussions can be threaded below the statistical tables. 

EDC helps companies replace out-of-control clinical studies with study management. This refers to the mechanical details of running a trial—keeping up to date on enrollment status, whether monitors have been checked, or if sites are entering data in a timely manner. These details streamline the process and make it easier.  

As more sponsors have experienced the benefits of this control, the demand for EDC and e-clinical systems has grown. In the near future, new study-management tactics are expected to drive even greater demand: 

  EDC systems have steadily added clinical-trial management functionality, including the ability to produce customized real-time reports. The ability to better see what is happening in a study makes management more timely, and more proactive—rather than reactive. In addition, EDC systems coupled with interactive voice response (IVR) technologies eliminate redundancies and discrepancies in front-end randomization data. They also integrate telephonic-based, electronic patient-recorded outcomes (e-PRO) data directly into the study database. These benefits make the whole process easier and simpler, with less manual effort.  

  Full-service EDC is an integrated process that includes the combination of technology with all other services to get the best possible results. It is an attractive option for sponsors that are resource-challenged or require additional data-management support. Some commonly requested full-service EDC offerings include data management, data integration, and statistical services.  

  EDC vendors have added features that eliminate the need to support and integrate multiple applications, including front-end document-management systems and  scheduling systems. This used to require tedious tasks like data re-entry, but since EDC already captures much of the data that drives these systems, it will make the process more efficient. 

If companies incorporate EDC into their clinical trials, there will be greater involvement ultimately with regulatory agencies in the sharing of ongoing study progress. EDC offers sponsors a variety of capabilities to improve the conduct of clinical trials. These capabilities include improved data capture, data analysis, and study management—all of the EDC "sweet spots." To understand how these capabilities simplify the conduct of a clinical trial, consider them in the context of therapeutic practice areas that have a high degree of complexity, or where the integration of data can facilitate the study.  

By leveraging these features, sponsors will be able to manage their studies more effectively—that benefits the subject and the sponsor. They also will be able to manage complex data, reduce errors, integrate information, and gain insight into trial trends. 

William Claypool, MD is CEO of Phoenix Data Systems. He can be reached at 

By leveraging EDC's features, sponsors can manage study progress better, adapt to opportunities, reduce trial times, and monitor patient safety.

Hitting the Sweet Spot

The past few years marked a low point in worldwide market launches for new active compounds. According to the IMS LifeCycle New Product Focus, pharma launched 31 new active substances worldwide in 2004, which was only one more than the 25-year-low in 2003, and down from 37 in 2001. It's not that companies weren't performing R&D—paradoxically, investigational drug applications to FDA reached 495 in 2004, passing a record of 415 that was set in 1998. 

The paradox is explained by attrition. According to the business intelligence company Pharma Projects, nearly 750 candidates were in Phase I trials in 2003 (up 85 percent from a decade earlier); nearly 1,250 were believed to be in Phase II (up 90 percent). But the number of candidates in Phase III was about 400, unchanged since the mid-1990s. The cumulative clinical-stage failure rate is now 80 percent, with 30 percent of new molecular entities failing in Phase I (mostly because of inappropriate pharmacokinetic or pharmacodynamic characteristics).  

Industry observers contend that outdated study models have been a real obstacle to change in pharma. But as new computational tools and microdosing methods emerge, researchers can help  companies change how they conduct studies, to make them cheaper, faster, and more effective. Why the steep failure rates and rising costs? A recent survey by Cambridge Healthtech Associates (CHA) locates specific reasons for the delays and failures of clinical trials in the many deficiencies in current clinical-trials protocols.  

  The main reason for delays? Recruitment of patients, mentioned by 68 percent of survey respondents. Just as commonly cited was study initiation, or the process of securing IRB approvals, inking contracts, and developing budgets. The most frequently cited reasons for the termination or failure of clinical projects were problems with efficacy (64 percent), inconclusive trial results (57 percent), and faulty trial design (43 percent). The respondents ranked the top-three reasons for termination of trials in order of priority, and responded as follows: inconclusive trial results, problems with efficacy, and commercial reasons (e.g., compound is misaligned with market need). 

  Pharma is spending more than ever on drug development. While the limited set of preclinical safety studies required to initiate Phase I might cost less than $2 million, the fully calculated cost of conducting a Phase III program can amount to several hundred million dollars easily—and it's rising. An economic model developed in 2003 by Bain Consulting showed that the total investment required to launch a drug increased from $1.1 billion between 1995 and 2000, to $1.7 billion between 2000 and 2002. During this period, the cost of discovery research remained static; the 55-percent increase was due almost exclusively to the clinical stages of drug development. 

  The real problem emerges when companies become burdened by the drug's post-marketing safety problems, even after it passes through clinical testing. According to a study from the Tufts Center for the Study of Drug Development, 3.5 percent of all the drugs approved for sale in the United States in the 1990s were withdrawn from the market subsequently; the rate has dropped to 1.6 percent since then, but there are numerous cases when approved drugs had to be withdrawn from the market soon after launch because of unexpected adverse effects. This indicates that the present drug-development process does not ensure safety early in clinical development. 

While cost doesn't seem to be the issue, the most obvious and urgent objective for the industry is to bring the clinical process under better control to ensure a drug candidate's ultimate success. But the industry's response to increasing clinical attrition has so far consisted mostly of efforts to streamline the existing processes without changing any of the fundamentals. 

This conservatism has a good reason, which is unrelated to science and technology: Major deviations from established regulatory pathways to approval would involve the risk of long delays and the probability of regulatory setbacks. Companies tend to move cautiously, mostly by using information technology to make patient data entry easier and less error-prone, but without fundamentally changing the clinical process. CHA's survey found that 45 percent of respondents described the culture or their clinical organization as risk averse. 

Pharma companies might be risk averse, but the industry has seen an increase in more fundamental attempts at change, such as introducing information-rich trial designs. The integration of pharmacogenomics was a relatively quick and easy process, but this has not been the case with pivotal or outcome measures like biomarkers. In its Critical Path document, FDA has outlined possible changes intended to speed the clinical trials process: The agency has signalled that it is willing not only to listen but to take the lead in an interactive process of change that should restore productivity to drug development. The Exploratory Investigational New Drug (IND) Guideline of January 2006 is the first concrete step towards opening the rigid regulatory framework to accommodate more relaxed and pragmatic approaches in Phase I. 

Companies are making efforts to implement key clinical technologies and practices into their existing systems (See "Facing Their Future"). There is a relatively high level of investment in biomarkers, EDC, and offshoring opportunities, but the current implementation of microdosing and adaptive design is extremely low. Microdosing allows an investigational drug to be administered to healthy volunteers at doses that are one percent or less of what is expected to have a pharmacological effect, and that must not exceed 0.1 mg. This practice allows an early assessment of pharmacokinetics, and might become a valuable tool for choosing the best of several related candidate compounds for actual clinical development. The rapid ramp-up in investment for microdosing over the next four years is important because it's an example of a restructured approach to clinical drug development—and an example of evolutionary new thinking. 

The full integration of information technology is the second arm of the new clinical-trials strategy, with a key role being played by pervasive computing—the trend toward increasingly ubiquitous computing devices in the trial environment. This starts with trial-design modeling, where companies like Pharsight have developed software packages based on existing toxicity information and pharmacokinetic and pharmacodynamic modeling to characterize and minimize the risk of failures. In this "virtual trial space," researchers can quickly explore multiple scenarios to optimize the design of individual trials, increasing the predictability of the process and the likelihood that each trial will give definitive results and lead to a successful program. 

A small part of these integrated efforts will be moving from paper-based trial documentation to electronic case report forms (e-CRFs). In the "e-clinical world," the investigator will see the patient's visit information, his study diary information and electronic laboratory results, even the genetic information of the patient. Patient compliance will be monitored by RFID chips, which also record details on how clinical supplies are distributed and stored. 

Applied systems biology (the modeling of key features of human organs or the entire human organism relative to health, disease, and pharmacotherapy) and the Virtual Patient (a computational model of human physiology in a particular disease state) are examples of holistic approaches to drug development that are also computation-intensive. Although this technology is still far from validation, partial models, such as Entelos' PhysioLab platform, already have been astoundingly successful. In another line, metabolomic "fingerprinting" of reactions to drugs, which is being pioneered by companies such as Metabolon, will supply clinicians and drug developers with nearly real-time information about metabolic shifts in individual trial participants.  

However, technology alone will not solve the problems of clinical and post-launch attrition. To accomplish this, the long-entrenched and rigid structure of the clinical trial process, with its stages I through III, will need to be entirely re-thought (See "Filling the Gaps").  Today's mega-trials, which strain logistic and clinical capacities, will have to be replaced by heavily IT-supported, post-marketing surveillance studies in the real-world environment. 

In 2015, what is now known as Phase I will assume a new role as a brief confirmatory testing stage of the model for drug and human interactions. Phases II and III will merge into a single, advanced-stage human testing phase that involves fewer patients than today, relying on relatively small populations that are highly homogeneous. Systematic post-marketing studies and an improved surveillance system will be integrated into a monitoring phase that documents real-life use of the licensed drug. The pre-approval clinical trial phase might be shortened to three years, with 40 to 50 percent of all candidate compounds that enter this stage completing it. This prediction model will allow developers to recoup costs and enjoy a longer life cycle under patent protection; it also will require pharma to pay closer attention to newly licensed drugs' real-life applications. 

Drug development's approval process will face complication and friction in the future because of increasing globalization that will require it to be introduced in an internationally harmonized fashion. The new clinical trials package should be completed by 2015, but resistance to any deviation from the well-established clinical-development process should be considered during the transition. There is, however, no other alternative—restoring productivity is always a question of survival for the pharmaceutical industry. 

 is founding director of HM Pharma Consultancy. He can be reached at 

 is general manager of advances reports at Cambridge Healthtech Associates. He can be reached at 

This prediction model will allow developers to recoup costs and enjoy a longer life cycle under patent protection.

A Clinical Sea Change

Three friends are talking over lunch. The first person declares, "I'm donating blood," to which his friends reply, "That's good." The second says, "I'm donating an organ." They all agree that it's great. When the third person announces, "I'm participating in a clinical drug trial," his statement is met with silence, confusion, then skepticism.   

Part of the reason surrounding patients' reluctance to become clinical-trial participants stems from a lack of direct and reliable information about clinical studies. Compounding that problem are the primary care community's reluctance to encourage patients to participate and pharma's negative image, which together have snowballed to create a shortage of clinical-trial volunteers. Without those volunteers, companies cannot bring new drugs to market. So industry needs to acknowledge the imperative—and embrace the opportunity—to present the  positive attributes of clinical-trials participation through targeted, thoughtful, and aggressive communications. 

Companies' reluctance to communicate information about clinical trials—combined with the sensationalism of consumer media—have overshadowed the benefits and successes of clinical-trial participation. High-profile stories involving drug-study conduct and misinterpretation of study results affect patients. One only has to look at early reporting of data from the Women's Health Initiative as an example. When information came out about possible side effects of the hormone Premarin, the media headlines screamed that the hormone caused heart disease, which caused widespread fear and panic. Stocks plummeted and funding immediately was halted. Although research later indicated that Premarin did 

 cause heart disease in women, the public already had a negative perception about the drug. This scenario proves that powerful messages can affect patients, physicians, and stock prices negatively by creating a disincentive for funding in areas that are being attacked. 

Acting the part:  An Iris Global model shows three distinct volunteer types, based on responses from patient focus groups on the likelihood of participating in a clinical trial.			

As the industry remains silent, the media has stepped in to "educate" consumers and practicing physicians. When consumer media 

 cover a specific clinical trial, the focus is often on scientific breakthroughs or other advances that may very well be far off.  

Plus, the story they're telling is not complete. Consumer groups don't understand why today's drugs are expensive, and they lack perspective on what it takes to get a new drug into their prescription bottles. As a result, the industry has a widespread patient-enrollment problem. The result is delayed trials—in fact, 80 to 90 percent of all clinical trials are delayed—and a more costly research and development process. 

It's not that communications efforts fail to target consumers. Mass advertising and public awareness about specific clinical trials has grown in refinement and effectiveness. But too often pharma leaves the clinical-trials communication up to investigation sites, which have scant resources and little direct-to-consumer experience. The result: ineffective ads that confuse instead of encourage potential clinical-trial participants. The public is left wondering if they have to surrender their current medications. Must they get permission from their physician, or worse, lose their physician loyalty? How will they find time away from work? And finally, are they just a pharma guinea pig? 

In an ideal world, primary-care physicians could be the solution to the dearth of trial volunteers. They're the key link to consumers. Focus groups have shown repeatedly that most patients prefer or require their physician's consensus before volunteering for a clinical trial. Patients cite the "trust" factor when considering participation. However, the majority of physicians in the United States are not involved in clinical studies, nor are they aware of specific trials available to patients. 

Doctors in focus groups say they want to keep it that way. The primary reasons doctors keep their patients in the dark about clinical trials are their own lack of knowledge on the subject and their fear of losing patients to another treatment center. The majority of doctors also say they decline to refer patients because studies offer them no opportunity to share in the research. And they're also concerned that trial participation is time consuming and inconvenient.  

According to a national study conducted on behalf of the Advancing Parkinson's Therapies (APT), the majority of physicians who treat Parkinson's do not refer their patients to clinical trials—even though most agree that it helps discover better remedies. Accordingly, very few patients report that their physicians have suggested participation in a clinical trial. Until practicing physicians incorporate the education aspects of clinical trials into mainstream medicine, patient referrals to investigation sites will be almost non-existent. 

When you get down to it, this unwillingness to refer patients can be traced back to a lack of the most basic information about clinical trials. Most primary- care physicians indicated they would consider referring patients to a trial only if the study sponsor sent information about the trial, possible benefits and risks of the treatment, and if they highlighted opportunities for doctors to participate in the research. Unfortunately, study sponsors rarely reach out to practicing physicians about studies in their communities. 

We cannot change the negative incidents, but the benefits of clinical-trial participation can be related through consistent public education. Positive messaging can have a significant impact on how quickly new therapies enter the market. The task isn't difficult, but it does require companies to have the courage to get out and open the doors of communication. 

The importance of awareness, collaboration, and participation require a concerted effort among small groups. But until recently, these initiatives were implemented independently and inefficiently. 

 Pre-education programs are an effective way to help potential participants gain knowledge about a future trial. The "Aware for All" program is a one-day educational conference developed by the Center for Information and Study on Clinical Research Participation (CISCRP), a non-profit organization conceived by co-founder and chairman Ken Getz. The program encourages consumers to meet with investigators, learn more about various clinical studies, understand the potential study treatment options, and learn concepts like informed consent, risk-benefit ratio, and participation. Since establishing the program three years ago, CISCRP has seen significant interest among the public wanting to learn more about clinical research. 

Pre-education programs can take the form of investigators presenting at grand rounds or network meetings. Letters sent to colleagues on a regular basis are effective ways to pre-educate physicians and nurse practitioners. But it's vital to communicate to consumers as well. The public needs reassurance about the benefits of participation and how the potential treatment may improve their quality of life. Instead of the current methods of filling the short-term goal of completing a specific study, the research communities need to take a longer-term view to increase future interest in trial participation. 

 In particular, pharma can do this better by following up with previous participants and educating them about future trials. Their exposure to the first trial enables them to experience that clinical studies typically do not pose significant health threats, so it's surprising that few—if any—comprehensive, relational databases have been developed for investigators to tap into for future trial recruitment. If the industry can apply the methodology used for observational trials—when companies track patient progress over time—to create a database for recruitment, the trial process can become more efficient. Companies can use this populated database to communicate with past participants, educate them about future trials, and even thank them for their participation—which can go a long way in building long-term relationships. 

 The 2004 institution of clinical-trial registries initially was viewed by some companies as another restriction imposed by the federal government. Pharma previously was not required to list every single trial they were conducting, and some felt the information overflow was confusing. But, in hindsight, clinical-trial registries offer the industry an opportunity to educate consumers, demonstrate the complexity of clinical trials, and perhaps trigger interest in participation—if they can use registries for educational purposes in addition to just compiling a list of trials. 

The scarcity of accurate information keeps the public ignorant, but education is the easy remedy. Informed consumers may want to discover new treatments by participating in clinical trials. 

 is senior vice president and managing director of Iris Global Trial Solutions, a division of Corbett Accel Healthcare Group. She can be reached at 

Three friends are talking over lunch. The first person declares, "I'm donating blood," to which his friends reply, "That's good." The second says, "I'm donating an organ." They all agree that it's great. When the third person announces, "I'm participating in a clinical drug trial," his statement is met with silence, confusion, then skepticism.

Failure to Communicate

I recently worked with a client on their clinical trial protocol for a huge study involving thousands of patients and hundreds of independent clinical investigators across the country. The study's protocol—the detailed plans and regimens that investigators must follow to test a drug in clinical development—was precise. Not only did it have lots of tests to determine the efficacy of the drug, but the protocol included a raft of criteria to ensure that only patients with a precisely defined set of health characteristics would participate in the study. 

However, the company felt that such a rigorous design would create some problems. By creating such careful screening criteria, it would be difficult to find enough patients to fill the trial. 

Because the tests to be administered were burdensome (such as multiple blood draws, 24-hour ambulatory blood-pressure monitoring), they might deter qualified patients from participating. 

The length and complexity of the protocol were bound to cause difficulties with patient drop-outs, driving up the time and cost to run the trial. 

The company's worries were well-founded—and they're not alone. Pharma manufacturers of every size are running into problems operationalizing the protocols they set forth for their clinical trials. 

Every R&D professional has a host of horror stories about protocols that went wildly awry: multiple amendments to the protocol, enrollment delays, and poor data quality, to name a few. But when asked, most people believe that the protocols are just fine—they see the science as generally strong, and the methodologies have a high likelihood of successfully determining the efficacy of the drug. 

This disconnect between people's perception of protocol quality (high) and actual protocol quality (low) has led us to believe that there are actually two different kinds of protocol quality. Through our conversations with heads of R&D, medical management, and clinical operations at a dozen large and medium-size pharmas, we've seen that R&D organizations are set up to focus on only one of them. This organizational stumbling block thwarts effective execution of the protocol, and costs the typical R&D organization millions of dollars a year in lost productivity and months or years in lost cycle time.   

This article explores these two types of protocol qualities. It offers some solutions to companies that want to improve protocol quality—based around execution and clinical trial operations—and in the process, bring their clinical trials under control, completing them on budget and on schedule. 

During the development of a clinical trial protocol, most pharma R&D organizations focus on "scientific" protocol quality—that is, making sure that the scientific goals of the protocol are sound and that there is a reasonable chance the protocol will achieve study goals. Questions such as, "What tests do we need to determine whether our drug is effective?" or "How many patients are necessary to assure statistical accuracy of our results?" receive well-deserved and careful attention. 

Protocol development teams often bring in medical consultants to help hone the scientific aspects of the protocol. But in their efforts, they often overdesign it, such as when they create too-stringent criteria for patient enrollment, making the protocol nearly impossible to execute. Protocol Review Committees tend to focus on the scientific aspects as well, poking and prodding the protocol to ensure it has a high probability of meeting its scientific goals. As a result, the team often amends the protocol, which then must be approved by FDA. Given that the average Phase III protocol has five amendments, costing almost $200,000 a piece in out-of-pocket costs, companies are spending nearly a million dollars on amendments per protocol. But when all is said and done, the scientific quality of a protocol tends to be reasonably good. 

There is a second type of protocol quality that is focused around the quality of the execution of the clinical trials. "Execution" quality addresses issues such as whether effective practices and processes are being used in the protocol; whether the protocol can be executed within the time and cost specified; whether the inclusion/exclusion criteria, procedures, visit schedule, etc. are necessary for the achievement of the protocol's goals and endpoints; and whether any of those events will hinder execution tasks such as subject enrollment/retention or data collection. While execution quality doesn't deal with the protocol from a scientific standpoint, it is nonetheless critical to a successful outcome. No matter how good the science is, a protocol that can't be executed effectively has very little real value. 

When considered together, these two types of quality complement each other: Scientific quality tends to expand a protocol's complexity in the name of good science, while execution quality tends to limit it in the name of efficiency and effectiveness. When they are in balance, the two work together to create an optimum protocol. Out of balance, the protocol becomes either too bloated to be executed effectively or too limited to achieve its scientific goals. 

Most organizations favor scientific over execution-protocol quality. At the base of that disconnect is the lack of any true ownership for ensuring optimal execution of trials. As a result, the clinical trial process rarely runs smoothly. 

R&D's scientific experts clearly own a protocol's scientific quality. They have the responsibility, the expertise, the authority, and the accountability for creating a scientifically high-quality protocol. However, the scientific experts usually hand off the protocol to operations experts for execution. 

It would be natural to assume that the operations experts own execution quality, but that's not the case. While operations experts have responsibility and expertise for creating execution quality, they generally only gain authority after the protocol is finalized. By then, the crucial execution-quality decisions have been made already. 

Rarely do scientific experts bring operations experts in as partners during the development of the protocol. That happens for several reasons. Often, the scientific and operational experts are siloed into medical and operations departments, and the "throw it over the transom" mentality presides in which one group independently develops the protocol and then simply hands it off to the second group to execute. Team-based organizations attempt to address this gap by creating a single, unified team. But execution experts remain left out of the protocol-development process because their position often is seen as subordinate to the scientific experts when it comes to protocol decisions. Even in a team environment, scientific experts' opinions receive undue weight, thereby rendering team-based decision-making ineffective. 

Furthermore, neither the scientific nor the execution experts have significant accountability for execution-quality failures. If a protocol runs late or over budget, management typically assumes external or other unknowable factors were to blame and no one is held responsible. And if the drug is successfully launched, virtually all execution problems are forgiven. The result is that poor protocol quality never gets resolved.  Enrollment and site problems crop up again and again but the root cause – poor execution quality – is never addressed and a huge amount of waste is allowed to occur during the protocol-execution phase. 

There are four steps companies can take to bring scientific- and execution-protocol quality into balance. 

1. Make the two types of protocol quality a management priority

. R&D management tends to focus on big picture issues and schedules, while the actual protocol quality, execution times, and budgets are delegated to lower level groups in the organization. These lower-level groups, such as the clinical teams or medical management and clinical operations groups, often have conflicting priorities and goals that prevent them from creating the balance between scientific and execution quality. For example, one group may develop milestone dates, but a different group is responsible for the quality standards associated with that date. 

Because of their exclusively big-picture perspective, management tends to assume that schedule and budget problems are an inevitable consequence of the development process. But trial budgets, schedules, and quality can be successfully managed, if measured. Senior executives should measure scientific quality, execution quality, and the success of each protocol. They also should set goals for execution quality and then insist on trial-over-trial improvement in meeting those goals. Management may insist, for example, that the organization's clinical trials move from 90% late to 50% late in the first year, followed by 25% late in the second. 

. Across the industry, no single R&D group has ownership for the end-to-end success of the clinical trial protocol. The only sure-fire way to solve this problem is to invest authority, responsibility, and accountability for protocol success in a single individual or group. 

Many pharmas have attempted to do this, most notably by creating a protocol manager or director position. However, history has shown that while this person ends up with responsibility for protocol success, he or she never has true authority to compel the compromises needed to solve conflicting scientific- and execution-quality requirements. The result is that these managers are perceived as ineffective, when in reality, they never had enough authority to be successful in the first place. 

To solve the problem, companies need to appoint an individual that sits above both medical and operations experts, and who has clear responsibility, accountability, and authority, as well as unwavering senior-management backing. This person ensures that execution quality concerns receive the same up-front attention as is afforded to scientific quality currently. 

. Typically, R&D management takes an authoritarian approach to the execution of clinical trials by dictating a schedule and budget. They set out schedules by saying things such as, "This trial needs to be completed in 18 months for $10 million." These budgets and timelines may fit nicely into management's overall product-launch scenario, but they often appear arbitrary and unrealistic to the folks who have to write and execute the protocol. In this way, they force the team to make unrealistic promises, skip crucial planning and review steps, and ultimately compromise execution quality. 

A better solution is to get senior management to (1) negotiate a viable clinical trial schedule and budget with the team that must write and execute the protocol, (2) hold that team accountable for achieving the schedule and budget, (3) provide executive support when hard decisions and compromises must be made, and (4) reward their success. 

Finally, it is critical to reward those teams that bring their trials to conclusion within their agreed-upon schedules and budgets, rather than rewarding those teams that miss their targets but then exert Herculean efforts to resolve the problems. 

4. Mandate the use of new tools and processes

. The typical protocol has a scientific review and a cursory enrollment feasibility analysis, but rarely anything more. Instead, the protocol teams need top-notch tools to obtain the most cutting-edge scientific and execution quality. In particular—if execution quality is really to be emphasized— management must supply more sophisticated tools and mandate that they be used via a systematic development and review process. 

Some of the tools that can be particularly effective at increasing execution quality include:

» Bayesian enrollment analysis conducted at the protocol synopsis stage to ensure an accurate enrollment forecast and optimized inclusion/exclusion criteria (this helps avoid amending the inclusion/exclusion criteria later and eliminates non-enrolling sites)

»  Walk-through of the protocol at the penultimate draft stage to ensure that visit schedules, procedures, and inclusion/exclusion criteria are in line with execution-quality requirements (this helps to ferret out execution problems that will cause data problems and amendments later)

»  Detailed, systematic, objective reading of the final protocol to remove inconsistencies, conflicts, and errors (this keeps investigators from getting confused and making protocol errors)

»  Protocol-quality checklist that provides the team with criteria for judging the quality of the protocol as they develop it (this helps the team incorporate lessons learned from previous protocols). 

In the face of time, budget, and staffing constraints, it is often convenient to skip these steps. However, there is ample evidence that skipping this up-front work results is scads of preventable errors that later end up costing much more in schedule, budget, and data quality. 

Shifting R&D to a more balanced focus on both scientific and execution quality will not be easy. Despite the rising costs and increasing timeframes of clinical trials, most R&D organizations seem unable to implement any fundamental, systematic improvements to protocol development and execution. Rather, they continue to make changes at the margins, where resistance to change—and positive impact on the bottom line—are minimal. 

Management should expect serious resistance to these efforts. Every argument from "the tools aren't useful in my situation" to "my trial is particularly difficult and therefore shouldn't be measured" or "the schedule and budget were mandated by others" will be put up in defense of poor performance. But by remaining steadfast, management will convey their resolve, and, eventually, the performance measures will start to show improvement. 

Taking aggressive steps to create ownership within the R&D organization of both scientific- and execution- protocol quality will yield significant increases in R&D value, from decreased costs per trial and increased staff efficiency to increased speed to market and increased portfolio integrity and flexibility. 

 is president of Customized Improvement Strategies. He can be reached at 

While execution quality doesn't deal with the protocol from a scientific standpoint, it is nonetheless critical to a successful outcome.

Trial by Design

Most clinical trial lawsuits filed against pharma companies stem from allegations that the investigational drug harmed participants. But how often do you read headlines about clinical trial participants protesting when a drug study is concluded because of safety concerns? While patients often don't want to continue a clinical trial after a drug is pulled for safety, what are the implications for pharmaceutical companies when they do? 

Such was the case in April and June 2005. Two separate groups of people who had been subjects in a Parkinson's disease clinical trial sponsored by Amgen, sued the pharma company in federal court for permanent injunctive relief and monetary damages. But unlike traditional clinical trial lawsuits, they weren't asking for compensation or damages. (

Instead, they wanted to force Amgen to continue providing them with the product. 

The cases involved a Phase II clinical trial to study the effects of a synthetic protein called glial cell line-derived neuroptic factor (GDNF), to which Amgen owned the rights. The study was designed to test whether GDNF would spur the growth of dopamine-producing cells and alter the course of Parkinson's disease (rather than simply masking its symptoms like currently available therapies). It began in 2003 and involved 34 patients at eight sites—including the Kentucky and New York sites where the plaintiffs participated. Prior to undergoing surgery to implant a pump, a necessary step to supply GDNF directly to the brain, each study subject signed an informed consent document. The consent provided that the study participants could elect to continue treatment for 24 months after the end of the study. But it also stated that investigators could withdraw a subject from the study if they found that the risk of continued participation outweighed the benefits, or if the sponsor decided to discontinue the study for a variety of scientific reasons. 

At the start of the clinical trial, Amgen hoped to see a 25-percent increase in subjects' scores relative to placebo after six months of treatment. By June 2004, however, the group using GDNF showed a bit more than a 10 percent increase, while the group using placebo had a 4.52 percent increase. Seven of the 34 subjects showed dramatic improvement, but four of those seven had received placebo. 

Since the results weren't up to Amgen's expectations, the company terminated all clinical use of GDNF in September 2004. It also cited two safety concerns: (1) the results of a primate study in which four of 44 primates given GDNF suffered cerebellar toxicity; and (2) the discovery that several human subjects had developed neutralizing antibodies. Amgen also cited lack of efficacy as a reason for discontinuing the study, stating that any positive effects experienced by the study subjects were from the placebo effect common in clinical trials for Parkinson's disease. Amgen consulted with FDA regarding the study's termination, and FDA agreed that the termination was reasonable in light of the scientific evidence. 

Upon filing suit in Kentucky and New York federal district courts, both groups of plaintiffs asked the courts to issue preliminary injunctions forcing Amgen to continue providing them with GDNF. They argued that GDNF was beneficial to them, and Amgen had contracted to supply them with the drug as long as it proved beneficial. They also said that in undergoing the pump implantation surgery, they had acted to their own detriment, relying on promises made by Amgen. Those promises were enforceable pursuant to the law of promissory estoppel. That doctrine provided that Amgen promised they would supply the drug to the participants, and since they promised to, it would be unfair not to follow through with their promise. Finally, by unreasonably denying access to GDNF, Amgen was breaching a fiduciary duty it owed them. After conducting hearings, both courts denied the requests. 

In their claims for breach of contract and promissory estoppel, the plaintiffs argued that the informed consent documents signed by study subjects constituted a contract and a promise on Amgen's part to continue treatment indefinitely with the investigational drug. They argued that, although the agreements were executed by the study subjects and the investigators (rather than Amgen itself), the investigators did so as Amgen's agents. Finally, the plaintiffs argued that Amgen was bound by the study investigators' statements that they would make decisions based on the patients' best interests, and that the subjects could continue to receive GDNF following the conclusion of the study if it proved safe and effective. 

Both courts disagreed. Noting that the investigators, and not Amgen, executed the informed consent documents, the courts found that Amgen had not entered into any contractual agreement with the participants. Citing the express terms of Amgen's clinical trial agreements with the investigators—which provided that the investigators were independent contractors, and which structured the study so that the investigators would conduct it independent of Amgen—the courts also found no actual authority on the part of the investigators to bind Amgen in any way. Lastly, the courts found that Amgen had not said or done anything which might have clothed the investigators in apparent authority to act on its behalf. 

In support of their breach-of-fiduciary duty claims, the plaintiffs argued that Amgen, working through the study's investigators, breached its fiduciary duty to ameliorate their pain and treat their illness with the best medicine available. However, the courts found no evidence that Amgen agreed its sponsorship of the study was undertaken primarily to benefit the participants. The courts further emphasized that the study was intentionally structured to foster independence and objectivity on the part of the investigators and their research institutions, thereby insulating them from any potential conflict of interest, which might arise from Amgen's involvement. For example, Amgen had not selected the subjects, met the subjects or known the details of the subjects' medical conditions. Given these considerations and the rigid FDA regulations, which govern the manner in which clinical trials are conducted, the courts found no factual or legal basis to impose a fiduciary duty on Amgen. 

Having lost in both Kentucky and New York, the plaintiffs appealed each of the lower courts' decisions. Although the New York plaintiffs later withdrew their appeal, the Kentucky plaintiffs continued. On March 29, 2006, the 6th US Circuit Court of Appeals in Cincinnati, Ohio, found in favor of Amgen and upheld the Kentucky federal court's ruling. 

represent important victories for pharma companies. Current FDA regulations governing the conduct of clinical drug trials mandate the respective responsibilities of investigators, institutional review boards (IRBs), and study sponsors. And, while compliance with regulations may not always constitute an absolute defense to liability, it is an important component of the defense, arising out of a clinical study.  

Those same regulations mandate that the study investigators must obtain the informed consent of each human subject to whom the drug will be administered, and that they are responsible for protecting the rights, safety, and welfare of subjects under their care. 

Had the courts found a contract to exist between Amgen and the participants, or had they found that Amgen owed them a fiduciary duty despite the fact that research was conducted by independent researchers, further litigation against the industry would have resulted. Litigation would have continued, not only by participants wanting to continue receiving investigational drugs after a trial's end, but by study participants hoping to take advantage of pharma companies' heightened obligations mandated by FDA's regulations governing clinical trials. 

 is senior associate at Sedgwick, Detert, Moran & Arnold in Dallas. He can be reached at 

The plaintiffs argued that Amgen breached its fiduciary duty to ameliorate their pain and treat their illness with the best medicine available.

The People vs. Amgen

Did you know that the first clinical trial was carried out between 605 and 562 B.C.? According to 

, King Nebuchadnezzar II ordered his subjects to follow a strict diet of meat and wine for three years. It wasn't until four children in his court convinced him to allow them to switch to bread and water instead that an endpoint was reached. After ten days, those in the  bread-and-water group appeared  resplendent—better nourished than those who had followed the meat and wine regimen. 

Fast forward to the 21st century.  The clinical-trials landscape has changed, to put it mildly. Instead of issuing royal decrees, pharma companies have compliance oversight procedures, policy guidelines, voluntary codes of conduct, and a host of rules. And with a scarcity of willing volunteers, pharma has to work harder to educate the public about ongoing clinical trials. In this competitive and fragile environment, individual drug companies aren't just keeping track of themselves—they're also keeping close track of their competitors. 

A 2005 KMR Group study laid a foundation for companies to understand how well they perform relative to their peers as well as provide insight into those factors most influencing productivity. The study found that clinical-operations productivity is generally increasing within the industry, most recently at an annual rate of seven percent. 

 takes a closer look at how fast the clinical-trials environment is changing, and what companies can do to keep up. 

The KMR study found that sites in Asia are enrolling a greater number of patients per site than those in North America and Western Europe. The team at A.T. Kearney discusses how pharma companies are in fact taking advantage of offshore opportunities, but they argue that pharma uses incomplete data to choose the best country in which to conduct a trial. Their solution? Use data-driven analysis to better identify offshore clinical-trials opportunities. 

Speaking of data, the study indicated that companies that rely on technology are more productive. William Claypool of Phoenix Data Systems sees this growing trend and discusses how the increasing use of electronic data capture (EDC) makes it easier to manage data and complete trials, particularly in complex disease areas like neurology and oncology.  

David S. Zuckerman of Customized Improvement Strategies has similar sentiments when it comes to trial design. Making protocol easy enough to execute, he suggests, ensures a successful outcome.  

Finally, Todd Betanzos, senior associate of Dallas-based Sedgwick, Detert, Moran, & Arnold, talks about the implications and outcomes for pharma companies when trial participants don't want a study to end. 

If Nebuchadnezzar and his court had dreamed of even half the health concerns we have today, they would have known that it is impractical to subsist on meat and wine, or even bread and water. And instead of royal decrees, they might have tried a little education about risks and benefits to help them stimulate enrollment. In that sense, at least, not much has changed in clinical trials  

 special projects editor. She  can be reached at 

Did you know that the first clinical trial was carried out between 605 and 562 B.C.? According to HealthandAge.com, King Nebuchadnezzar II ordered his subjects to follow a strict diet of meat and wine for three years. It wasn't until four children in his court convinced him to allow them to switch to bread and water instead that an endpoint was reached. After ten days, those in the bread-and-water group appeared resplendent-better nourished than those who had followed the meat and wine regimen.