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CRO/SPONSOR : Personalized Medicine Development - Role of CROs  TRIAL DESIGN : Eye Movements Help Determine Side Effect Profiles  SUBJECT RECRUITMENT : Connecting Type 2 Diabetics to Clinical Trials  INFORMATION TECHNOLOGY : Cloud Computing Brings Efficiencies to Life Sciences  Also in this issue : Biosimilars Development, Funding in Europe, Transforming R&D, Subject Protection in India

Applied Clinical Trials Digital Edition - July 2011

Many patients with a chronic medical condition are interested in finding new and improved treatments for their disease. One method of achieving this is through participation in clinical research. According to a survey of participants,

  two primary reasons patients participate are: potential benefit to themselves or other patients and to enhance knowledge and understanding of their disease. 

As researchers work on improving medical treatments for patients, there is often a disconnect coordinating and connecting interested patients to the clinical trials. Understandably, with sponsors spending an average of $7,500 to recruit a single patient for a Phase III clinical trial, linking patients to the correct clinical trial is challenging and expensive. Improved search platforms have been developed that are patient friendly, allowing patients to navigate the complicated and medical terminology laden clinical trial descriptions. These provide search results of trial opportunities that match their medical condition and are close to where they live. 

US clinical trials segmented by therapeutic area show metabolic/endocrinology related trials as one of the larger segments being studied. Diabetes is a large component of this segment. In 2011 the estimated prevalence of diabetes was 25.8 million people (8.3%) of the US population.

  Diabetes mellitus is a chronic disease requiring long-term medical care to restrict the development of complications and manage them as they occur. Type 2 diabetes mellitus (T2D) was referred to as adult onset diabetes, typically affecting patients over 40 years old. Because of the epidemic of obesity and the inactivity of children, it is occurring in ever-younger ages. T2D is characterized by peripheral insulin resistance with a varied insulin secretory defect. About 90% of patients who develop T2D are overweight with insulin resistance and lack the ability to increase beta-cell production of insulin. The morbidity and mortality associated with diabetes are related to the short- and long-term complications. These complications include: increased risk of infections, microvascular complications (retinopathy, nephropathy), hypoglycemia and hyperglycemia, macrovascular disease (CAD, stroke), and neuropathic complications. The prevalence of T2D varies widely among various racial and ethnic groups—the fastest growing racial and ethnic groups are Native American and Alaska Native. The risk of retinopathy and nephropathy appears to be highest among blacks, Native Americans, and Hispanics. 

Many people who take part in studies believe that doing so will benefit themselves and possibly others by increasing life expectancy or reducing suffering now or in the future (Figure 1). The advances in what are known about their disease and medications that they may take now are available only because people before them volunteered to participate in clinical trials. Another reason to consider participation is the access it affords to leading healthcare professionals and potentially useful new therapies that are usually free of charge and are provided under high standards of care.

Figure 1. Survey takers were asked: Which of the following is the most important reason you might consider participating in a clinical trial? 

In a recent survey, 355 patients with diabetes were asked about their background, income level, medication use, clinical trial involvement, overall experience, and reasons for participating in clinical research (the demographics of respondents are provided in the online version of this article). 

Noteworthy survey findings include: 57% of patients had not previously participated in a clinical trial, of those patients, 55% had never really considered nor talked with their doctor about clinical trial participation.  

Of the patients that had participated in a clinical trial, there was a wide range of times since they had first enrolled in a clinical trial (less than six months to more than 10 years). When asked about their experience in clinical trials, 88% rated their experience as positive to very positive and 88% would recommend clinical trial participation to other patients with diabetes. Additionally, 88% of patients indicated that it was likely or highly likely they would consider participating in another clinical trial.  

Pew Research reported that 80% of online Americans search for health information on the Internet and an overwhelming majority of patients (75%) feel reassured or empowered with the ability to search and satisfy their information needs.

A common site when beginning an Internet-based search is 

. Since 2008, it has been required by law that all clinical trials in the United States are listed on the 

 website. While it is comprehensive, it is heavy in medical jargon and does not have some of the key functionality needed for helping educate patients.  

The search process for clinical trials is a barrier, even for motivated patients. When considering how patients learn about clinical trials and gain access, Internet-based searches are the obvious starting point, and often the primary source for consumer health information. Simon and Hegedus, examined website content that provided details about cancer clinical trials using popular search engines.

Of the 66 sites they reviewed, many provided detailed information about cancer clinical trials and about half offered some form of clinical trial search function. Their conclusion was that clinical trial websites provide benefits, including access to information about clinical trials and links to clinical trial search tools. Unfortunately, however, the amount and diversity of this information, the difficulty of the language used, and the potential lack of confidentiality may all be barriers to a patient finding the right trial.  

As patients search for clinical trials, only 14% obtain information from their physicians whereas 44% find out about clinical trials through media. Another small percentage of patients are referred to clinical research by family members or friends. Researchers and sponsors are using the power of the Internet to help people identify and enroll in studies. In a recent NIH study, content analysis revealed that clinical content is highly variable on these sites.

Most require users to be fairly knowledgeable about their medical condition and quite adept in their web navigation skills. In order to identify a potential trial, patients must comprehend the medical terminology related to their condition and understand the potential treatment or intervention. This is combined with a need to understand the general clinical trial research process while learning the demands of a specific trial to determine their interest and eligibility.  

Often patients begin their search for clinical trial information on familiar sites, such as YouTube and Google, where site navigation is familiar and straightforward. Other websites' (i.e., 

) health discussion forums are emerging sources to obtain general health information.  

The more sophisticated patients may search the NIH website or go directly to a pharmaceutical company's site known for producing their medication. Social media and blogs are rapidly becoming popular sources for clinical trial information. For example, research sites and academic medical centers are beginning to use Facebook links to their trials. 

To optimize success in identifying a clinical trial that a patient is qualified to enroll in, a search tool needs to provide a comprehensive listing of all clinical trials without complex medical jargon and provide some basic patient educational information in a user-friendly format. 

The clinical trial search process by and recruitment for patients needs to be continuously updated and improved. In addition to gaining input from patients to simplify and enhance their search options, developers should share these tools with healthcare providers and their staff to integrate patient recruitment into the clinical encounter. 

PhD, is President at Corengi, 7054 Mary Ave. NW, Seattle, WA.

*To whom all correspondence should be addressed.

1. D. Wendler, B. Krohmal, E. J. Emanuel, and C. Grady, "Why Patients Continue to Participate in Clinical Research," 

2. National Diabetes Information Clearinghouse, "National Diabetes Statistics, 2007," 

http://diabetes.niddk.nih.gov/DM/PUBS/statistics/

3. The Center For Information & Study on Clinical Research Participation, "Clinical Trial Facts & Figures for Health Professionals," 

http://ciscrp.org/professional/facts.html

http://www.pewinternet.org/Reports/2006/Online-Health-Search-2006

5. C. Simon and S. Hegedus, "Exploring Websites on Cancer Clinical Trials: An Empirical Review," 

6. N. L. Atkinson, S. L. Saperstein, H. A. Massett, C. R. Leonard, L. Grama, and R. Manrow, "Using the Internet to Search for Cancer Clinical Trials: A Comparative Audit of Clinical Trial Search Tools," 

Feature Article

The disconnect coordinating and connecting interested patients to clinical trials is an ongoing struggle.

Recruiting Diabetes Subjects

Over the last 20 years there has been a significant change in the approach that is taken to the early stages of clinical development. The initial studies of a molecule in man are no longer focused purely on safety, tolerability, and PK but are layering in techniques to better understand and characterize a molecule in terms of putative efficacy, both wanted and undesired side effects, time course of pharmacodynamic effects, and competitive performance to existing therapies.

The drive for the change has come from the industry itself which has been faced with rising R&D expenditures and a high fail rate of molecules in expensive patient trials. The pressure has grown to reduce development time lines, decrease overall development costs and make go/no-go decisions on compounds at an earlier stage.  

At the forefront of this change has been the inclusion of often simple physiological measures into the first in man trials that can be used to provide some of this pivotal information. To illustrate the use of these techniques this article will explore how two simple techniques involving measurements from the eyes, saccadic eye movements, and pupillometry, are being applied to investigate the side-effect profile of compounds, better understand the mechanisms involved in the pathophysiology of CNS disease states and demonstrate target engagement of drugs.  

A saccadic eye movement, or saccade, occurs when a human changes their direction of gaze from one point to another (Figure 1). The decision to initiate a saccade is under voluntary control, however, once the saccade is initiated the speed that the eye moves is completely involuntary with no central CNS influence. 

Saccadic velocity has been shown to be adversely effected by compounds that cause sedation. A number of studies have reported that ethanol will induce a decrease in saccadic velocity at very low doses where the subjects are unable to qualitatively self-report feelings of sedation.

  Decreases have similarly been shown when subjects have received compounds that induce symptoms of sedation such as benzodiazepines and opiates. 

Measurement of saccadic eye movements under controlled laboratory conditions therefore presents an opportunity to characterize the sedative effects of any compound. To understand and interpret the clinical relevance of any changes in this parameter it is essential that researchers measuring saccades benchmark the technique against a wide range of compounds known to induce sedation that work via contrasting pharmacological mechanisms.  

Measurement of saccadic eye movements can be performed in a number of different ways. The most common include using electrooculogram (EOG) electrodes positioned at the upper and lower canthus of the eye to detect muscle movement, and the use of infrared detectors focused on the eye using a device known as a saccadometer. Subjects are asked to focus on a sequence of lights, which may either be presented on a light bar or projected using lasers in front of them, and to follow the lights with their eyes as quickly and accurately as possible. Common to both the EOG and infrared approach in any commercially available system is a software package that can analyze the incoming signal from the eye and automatically derive a range of outcome measures including peak saccadic velocity and the latency of saccadic initiation.  

As part of our validation of saccadic technique, we investigated the effects of an increasing dose of buprenorphine on the velocity of saccades in 16 healthy male volunteers (Figure 2). A crossover design was employed so that all volunteers received all treatments in a pseudo-random order. A one week washout was allowed between treatments. Volunteers receiving placebo showed little variation in velocity of saccades over the 24-hour period following treatment administration, however buprenorphine appeared to induce a decrease in saccadic velocity peaking around two hours post dose. Magnitude of deficit of response was demonstrated to be dose dependent.

Figure 3 presents a plot of concentration vs. response for a novel compound that induced significant sedation. It was possible to model a strong PK-PD relationship for this outcome measure. This modeling of concentration against effect can provide pivotal information on target concentration for future studies and help in the selection of dose and dosing regimens for future studies. The study clearly indicated that at doses above 100 ng/mL significant sedation was occurring in the single ascending dose study, an undesirable profile for a potential drug. However, we were able to demonstrate in the multiple ascending dose study that when these concentrations were built up over the course of a few days, no impairment in saccadic velocity was reported. Taken together these results helped guide the dosing regimen for the subsequent patient trials.

The two examples illustrate how the pharmaceutical industry is applying saccadic eye movements both in individual targeted studies focusing specifically on pharmacodynamic parameters and also as part of first-in-man studies where the PD data is a secondary objective of the trial. In both cases saccadic eye movement is a fast, highly sensitive and non-invasive measure. Combined with the involuntary nature of the response, this makes it a powerful, objective marker of sedation that can easily be included in early clinical trials to screen for sedation.  

In addition to playing a role in profiling a compound in healthy volunteers, the unique properties of saccadic eye movements can be used to better understand disease states. The study of eye movements as a trait marker for schizophrenia has been documented for over 40 years. The most marked effects have been seen when the saccade task described above is adapted to become an antisaccade task (Figure 4). In the antisaccade task subjects fixate on a central light. This light goes off and is replaced by a light on the periphery that is to the left or right. Subjects are instructed not to look at the new light but instead to fixate on an equivalent position on the opposite side of the central light (i.e., if the light is 10 degrees left of center they should look 10 degrees right of center). This task tests the ability to restrain the natural impulse to look at the light and requires significant frontal lobe/executive control. It is a difficult task with even healthy controls looking in the wrong direction around 20% of the time. 

Schizophrenic patients have been shown to demonstrate significantly greater numbers of errors on this task compared to healthy controls with error rates of greater than 50%. Interestingly, studies in first-degree relatives of patients with schizophrenia have also been conducted. Error rates in relatives appear to split into two distinct groups with some performing like healthy volunteers and others having high error rates like their patient relatives. This suggests that the outcome measure could be of relevance to familial trait characteristics in schizophrenia.

As the antisaccade task requires significant frontal lobe function, the test has been used to investigate the hypothesis that the ability of atypical neuroleptics to improve the negative symptoms of schizophrenia is due to enhanced frontal lobe function. Eighteen patients stably maintained on depot neuroleptic medication were co-administered the 5-HT antagonist cyproheptidine, known to improve frontal lobe function. Significant improvement in antisaccade error rate was detected, supporting the role of the frontal lobe in controlling this function.

Measurement of pupil diameter has been shown to be a sensitive and objective marker of autonomic activation

  and a validated marker of drug activity on the autonomic nervous system.

In this test, subjects sit in front of an infrared camera under standard low-light conditions. The camera is focussed on the pupil. Measurement of initial pupil diameter is recorded directly and the pupillary constriction response (latency, amplitude, and duration) to a flash of light is also measured. 

Opiates are known to cause constriction of the pupil and therefore this technique can be used to detect and quantify opiate response. 

Figure 5 illustrates the effects of two gold-standard opiates, morphine and tramadol. Morphine induces a rapid and significant decrease in pupil diameter, reducing it by approximately 40% within the first hour of dosing. This effect is still ongoing by five hours post-dose although it is beginning to recover by this stage. The effect of tramadol is a much smaller and delayed response with no significant decrease in pupil size seen until two to four hours post-dose. The effect on pupil diameter is controlled by action on the mu-opioid receptor. Morphine has high affinity for this receptor and hence a strong, immediate effect is seen. In contrast, tramadol has low affinity for this receptor, though some of its metabolites do have greater affinity, and hence a delayed change is observed.

As with saccadic eye movements it is possible to use the technique for modeling concentration vs. dynamic effect. PK-PD modeling allows for a greater characterization of the effects of the novel opiate, including the calculation of concentration required to produce maximal effect. This can be invaluable information for designing an appropriate patient study. 

Pupillometry can also be applied in patient trials to provide added-value information and in better characterizing the pathophysiology of a wide range of disease states. One area where the technique has been applied longitudinally to monitor disease state is with neuropathy associated with diabetes. A number of studies have shown that pupil reaction to ocular light stimulation deteriorates as the condition progresses, both in terms of pupil diameter, reflex amplitude and constriction velocity.

  Pupillometry can therefore be used to track improvements to the progression of the disease made following pharmacological intervention. 

Pupillometry is also used extensively in research into sleep disorders where significant changes in pupillary response have been detected in conditions such as sleep deprivation and hypersomnia and therefore this method allows evaluation of potential therapies in these and other related disorders such as sleep apnea. Pupillometry can also play a role in migraine research. Studies have been carried out using pupillometry to measure changes in pupillary light reflex in the period following migraine headache. Decreases in both the amplitude and speed of the constriction response in these patients indicated the potential involvement of the parasympathetic nerves supplying the eye in migraine headache. This enabled a better understanding of the pathophysiology of this disease and led to the development of targeted drug therapies.

Due to the alterations in pupillary reaction seen with opiates and other illegal drugs there is a potential for the use of pupillometry as a non-invasive physiological method of detecting drug-related impairment. Both pupil diameter and pupillary constriction response are affected by a range of drugs including marijuana, stimulants, tranquilizers, and opiates such as cocaine and heroin suggesting that pupillometry could provide a more effective and less costly alternative to urinalysis-based drug testing.  

The application of specific techniques to better characterize the pharmacodynamic effects of a drug are becoming commonplace in early phase trials. Key to the success of these tools is to select the most appropriate technique that is well-validated and has proven effects with compounds of similar target indication or class. 

Data from these trials can be pivotal in guiding the dose selection for future patient studies and in identifying unwanted pharmacodynamic effects of a drug at an early stage. This illustrates the positive contribution that pharmacodynamic measurements can make in accelerating a cost-effective early clinical development program. 

 is Manager Clinical Pharmacodynamics at ICON Development Solutions, Skelton House, Manchester Science Park, Manchester M15 6SH, UK.

1. L. Holdstock and H. de Wit, "Ethanol Impairs Saccadic and Smooth Pursuit Eye Movements without Producing Self-Reports of Sedation," 

Alcoholism: Clinical and Experimental Research, 

2. T. J. Crawford, T. Sharma, B. K. Puri, R. M. Murray, D. M. Berridge, and S. W. Lewis, "Saccadic Eye Movements in Families Multiply Affected with Schizophrenia: the Maudsley Family Study," 

3. I. B Chaudhry, S. D Soni, J. S. E Hellewell, and J. F. W Deakin, "Effects of the 5HT Antagonist Cyproheptadine on Neuropsychological Function in Chronic Schizophrenia," 

4. J. Grünberger, L. Linzmayer, M. Grünberger, and B. Saletu, "Pupillometry in Clinical Psychophysiological Diagnostics: Methodology and Proposals for Application in Psychiatry,"

 Israeli Journal of Psychiatry and Related Sciences,

5. V. Koudas, A. Nikolaou, E. Hourdaki, S. G. Giakoumaki, P. Roussos, and P. Bitsios, "Comparison of Ketanserin, Buspirone, and Propranolol on Arousal, Pupil Size, and Autonomic Function in Healthy Volunteers,"

6. K. Thamotharampillai, A. K. F. Chan, B. Bennetts, M. E. Craig, J. Cusumano, M. Silink, P. J. Oates, and K. C. Donaghue, "Decline in Neurophysiological Function after Seven Years in an Adolescent Diabetic Cohort and the Role of Aldose Reductase Gene Polymorphisms," 

7. V. Mylius, H. J. Braune, and K. Schepelmann, "Dysfunction of the Pupillary Light Reflex Following Migraine Headache," 

Two unique techniques help characterize pharmacodynamic drug effects in healthy subjects.

Eyes Play a Focal Role in Research

"Failure to generate, support, and implement research means that patients are missing out on ground breaking new procedures and therapies." Does this sound familiar? And what about this? "There are challenges in designing appropriate trials and recruiting patients to them." Or this? "High quality research is essential for improving patient care and outcomes. Without the investment that enabled their development, the advances that benefit patients today would not have been possible. We cannot afford to discourage innovation." 

Of course it all sounds like more of the same. This is the message that the European pharmaceutical industry has been delivering over and over again for years now, as it sees its research base threatened with erosion in the face of international competition and ever-tighter European drug pricing rules. 

But this time it isn't the pharmaceutical industry. It is a rival for the sort of support that research-based drug manufacturers are constantly striving after. With only a few minor omissions, the extracts are taken word-for-word from a new report launched in mid-June by the United Kingdom's Royal College of Surgeons (RCS). The report constitutes an urgent plea for attention—and it cuts right across the ground that innovators in the world of medicines consider their own. 

It complains, for instance, that in 2009 just 11 surgical trials were funded by the United Kingdom's principal health research bodies—"despite the fact," continues the RCS, "that one in four procedures in the national health service are surgical." By contrast, it says, there were more than 250 applications for Phase I trials for medicines and more than 800 approvals for post-Phase I trials. While the pharmaceutical sector spent more than $5 billion on research in the United Kingdom, currently only 1.5% of the $2 billion of annual UK government funding into medical research goes into surgical research, the surgeons lament: "Support for academic departments of surgery is declining as public and university funding is increasingly focused on other areas of biological science." 

There is worse to come in terms of jockeying for position. "Surgery cures more cancers than any other form of intervention, including radiotherapy and chemotherapy," says the RCS. "Continued development and research into these types of curative treatments is vital." But lack of recognition "makes it difficult for surgery to compete for funding with other types of research." 

A particular target of its attacks is "funding bias towards drug therapies" and "randomized clinical trials for drugs." The report recommends "a full review of public funding of translational research." One of the key concerns that the RCS sets out is that surgery is not incorporated sufficiently in the world of clinical trials. The sense of disappointment is articulated by Professor Martin Birchall, a UK consultant surgeon who is a pioneer of laryngeal and stem cell transplantation: 

"For innovation to become a widespread part of new clinical practice," says Birchall, "effort, time, and cost needs to go into detailed laboratory work, meeting the public safety requirements, and finally performing often difficult clinical trials." And here things break down, he suggests. Moving into clinical trials "can seem so daunting that the amazing group of innovator-surgeons we are gifted with in the United Kingdom can often be discouraged from taking their ideas and science into the clinic."  

By a curious coincidence, the RCS released its report on the same day that the European research-based pharmaceutical industry was holding its annual general meeting in Brussels. By something less of a coincidence, the principal declarations from the drug manufacturers were not dissimilar to those from the surgeons: most of the message can be summarized as "We are of vital importance, we are massively underestimated and undervalued by many healthcare authorities, and particularly victimized by myopia and short-termism among those responsible for healthcare budgets, who regretfully fail to see the broader picture and treat us as we deserve to be treated..."  

By another curious coincidence, however, EFPIA—now under new management—is also talking of presenting itself as a partner in healthcare provision, of widening its own approach to the debate so as to take broader account of healthcare systems, of being cooperative and constructive, and of seeing the questions of drug provision from the point of view of the authorities and other healthcare players, rather than just through the perspective of the manufacturers. Now curious observers will have the opportunity to see whether the drug industry tries to meet the surgeons halfway—or whether each side will continue to fight its patch on its own terms. 

The new management at EFPIA, incidentally, is Richard Bergström, a Swede with a background in both regulation and the pharmaceutical industry, who has just taken over as director general. It is he who has been championing the "partnership" approach for the industry—he characterizes himself as a man of dialogue, keen to build trust. 

He has wasted no time in trying to reinforce trust in some of the activities of the industry that have provoked controversy—and indeed vigorous criticism—in Europe. At his very first annual meeting of the organization he has just joined, he pushed through changes to the industry's codes of conduct on sampling and on company links to patient associations. 

In eastern Europe in particular, the industry has been repeatedly challenged for its very liberal interpretation of what constitutes exceptional circumstances that justify sampling. Providing samples to healthcare professionals is, in principle, against the law in Europe—but there are exceptions. To familiarize doctors with new medicines, some limited sampling is countenanced. The industry has reached broad agreement that four small packs of a new medicine can be given to a doctor each year for two years, as long as the doctor makes a request in writing. Those two years have been stretching out rather longer in some of the EU's newer member states—those that came in from the cold after the fall of the Berlin Wall—and Bergström has persuaded the associations and companies that are EFPIA members to curb their enthusiasm for largesse. 

Of more interest to clinical trialists are the updated provisions of the EFPIA code on contacts with patient associations. These groups frequently play an important role in highlighting rare diseases, in providing access to potential trial subjects, and in advocacy. Unsurprisingly, each company will have to make publicly available a list of patient organizations that it supports, financially or otherwise, starting next year. The list will have to permit "the average reader to form an understanding of the significance of the support," including "the monetary value of financial support and of invoiced costs," and the description must state the amount of funding and the purpose (such as an unrestricted grant, a specific meeting, or publication). 

For "significant non-financial support that cannot be assigned a meaningful monetary value," such as the donation of public relations agencies' time and the nature of their involvement, companies must clearly describe the benefit that the patient organization receives. Companies must also ensure that their sponsorship is always clearly acknowledged and apparent from the outset.  

EFPIA also introduced new rules on contracted services—which patient organizations increasingly provide as consultants to industry, including as experts and advisors for participation at advisory board meetings and speaker engagements. These rules require each company to make publicly available a list of patient organizations that it has engaged for such services, and the total amount paid per patient organization. Other limitations imposed are that contracts between companies and patient organizations under which they provide any type of services to companies are only allowed if such services are provided for the purpose of supporting healthcare or research. Compensation for services must be reasonable and "not exceed the fair market value of the services provided," and token consultancy arrangements may not be used to justify compensating patient organizations.  

Elsewhere, the text recognizes that the industry "has many common interests with patient organizations, and expects that relationships take place in an ethical and transparent manner." The code also insists that "the independence of patient organizations, in terms of their political judgement, policies and activities, shall be assured." Pharmaceutical companies must not seek to influence the text of patient organization material they sponsor in a manner favorable to their own commercial interests.  

The rules extend to events and hospitality involving patient associations. All events sponsored or organized by or on behalf of a company must be held in "appropriate locations and venues that are conducive to the main purpose of the event, avoiding those that are 'renowned' for their entertainment facilities or are 'extravagant.'" All forms of hospitality provided by the pharmaceutical industry to patient organizations and their members shall be reasonable in level and secondary to the main purpose of the event, whether the event is organized by the patient organization or the pharmaceutical industry. Hospitality extended in connection with events shall be limited to travel, meals, accommodation, and registration fees. 

No free lunches, then. That is a lesson that the European pharmaceutical industry appears to be starting to learn, too. Bergström likes to say that if the industry wants to be treated as a partner, it must behave as a partner. It is going to have to abandon some of the presumptions that it has entertained over recent decades, which have deluded it into the belief that it is immune—and deserves to be immune—from public and economic pressures. 

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

View from Brussels

A newly released report has the pharma industry facing some new rivals.

Fighting for Territory and Funding in Europe

Cloud computing is a relatively new phenomenon in the life sciences industry that many pharmaceutical companies and contract research organizations (CROs) are just beginning to adopt. Companies are looking to gain a better understanding of what cloud computing is, where its application makes sense in their world, and whether its web-based infrastructure complies with strict internal and regulatory requirements for data security and process in an increasingly globalized industry. 

There is a spotlight on cloud computing because of its potential for streamlining clinical development processes, accelerating timelines, and cutting information technology (IT) costs. Initial efforts in life sciences have mostly concentrated on more efficient handling of the volumes of data generated by the R&D process, but there are also emerging clinical trials applications. Specifically, optimizing the way documents from multiple sources are collected, exchanged across a network, and archived is a significant focus. With tight security in place, document-centric processes involving internal and external stakeholders can be centralized, automated, and monitored in the cloud, which greatly improves operational efficiency. As research and development, complex protocols, and regulatory compliance activities are generating massive numbers of documents, traditional paper-based or simple desktop methods of document handling are becoming unsustainable, making the cloud an attractive alternative.    

But what exactly is the cloud? This article attempts to answer this question from the perspective of the life sciences industry, which has concerns surrounding the security and compliance of the cloud. This article will also provide some practical considerations in selecting cloud solutions for clinical trial operations.   

Cloud computing is a catchy term that refers to delivering hosted services over the Internet.

 It is an environment in which software does not reside on desktops, but rather resides on a web-based server with shared virtualized resources. Software is available on-demand, similar to what consumers experience when they download apps on their smartphones or personal digital assistants. This delivery model has the benefit of extending IT's capabilities for accessing web-based applications in real time while reducing the cost and footprint of the internal IT infrastructure. 

The architecture behind cloud computing is a massive network of interconnected servers, often with a user-friendly front-end interface, which allows users to select services. These services have three characteristics that distinguish them from traditional hosting:

They are available on demand, and can be subscription-based or pay-per-use 

A user can have as much or as little of a service as it wants

The service is hosted, managed, and maintained by the provider, meaning that the user needs only a device and Internet access

Besides the architectural component, cloud computing allows for a flexible operating platform. This means that in contrast to the traditional approach of using systems and processes that have been hardwired to particular technologies and providers, cloud computing offers a technology environment that changes the nature and economics of data exchange. The benefit of this platform is that companies can create a more open and responsive environment for innovation.

The cloud platform has evolved to include an array of providers whose offerings fall into three broad categories: Software-as-a-Service (SaaS), Infrastructure-as-a-Service (IaaS), and Platform-as-a-Service (PaaS) (Figure 1). There is no requirement for upfront capital expenditure with any of these cloud configurations, so choosing the right cloud structure is a function of a customer's need to communicate outside firewalls, need for mobile access, interest in limiting upfront costs, scalability requirements, and high collaboration requirements. 

Figure 1. Offerings fall into three broad categories. 

Use of the cloud is expanding in the life sciences sector, with most of the emphasis on R&D activities and clinical trial management. Eli Lilly, for example, started using the cloud in basic research to accelerate the speed of development with less IT intervention, and to address the issue that the company's IT infrastructure was operating at full capacity.

, the company was under pressure to reduce fixed IT costs without compromising service levels; Eli Lilly began working with a cloud provider to offer computing capabilities to its global network of scientists.

The resulting efficiencies have been quite compelling.  The company was able to launch a 64-machine cluster computer working on bioinformatics sequence information, complete the work, and shut it down in 20 minutes, all for the cost of $6.40. To achieve that same process internally would have required 12 weeks of work.

Similarly, for the past few years, the Pharmaceutical Research and Development IT organization at Johnson & Johnson (J&J) has been researching different models and providers of cloud computing to significantly expand computing and storage capabilities for its research and data-crunching functions.

  The company is working with business partners to move applications out of the grid and into the cloud, which will represent a growing portion of the company's IT expenditures.

  J&J Pharmaceutical R&D has been moving research projects to the cloud and is also looking to this technology to handle resource-intensive projects such as analyzing filing data for drug approval. 

In January 2010, a survey of R&D researchers highlighted the growing acceptance of cloud computing within life sciences expected between 2010 and 2013.

  Of the 49 respondents, representing an array of large, mid-sized, and small pharmaceutical companies and academic institutions, more than half projected at least 11% of their IT budget over the three-year period will be dedicated to cloud computing. As a hint of things to come, 9.1% expect more than 50% of their IT budget will be allocated to cloud computing resources by 2013 (Figure 2).

Figure 2. Expected percentage of R&D budget devoted to cloud computing from 2010 to 2013. 

Although cloud-based efforts in life sciences started primarily in basic research, the cloud is playing an emerging role in streamlining the heavily regulated world of clinical trials. During the start-up phase of clinical trials, for example, volumes of documents need to be exchanged with investigative teams around the globe, including protocols, investigator brochures, and budget work sheets, to name a few. Efforts by the investigative sites and other players to complete all of these documents can be a major obstacle to timely study start-up.

  Oftentimes, these processes are still handled using manual, paper-based methods such as unsecured e-mail, which does not track version changes or create a reliable audit trail. In a 2009 study of 252 investigative sites, 67 percent of respondents indicated they use unsecured e-mail as the primary method of document exchange during clinical trials.

  As further evidence of inefficiency, in the same study, one-quarter of investigative sites reported wasting more than three hours weekly searching for study-related documents.  

The cloud transforms this labor-intensive process into one in which document exchange is efficient, secure, and controlled. As teams are no longer bound by the physical limits of paper, the cloud shifts the focus to the data contained within documents, and not on the administrative management of the static documents themselves. The data becomes essentially freed within the cloud and can be tracked, stored, and reused as necessary.   

The issue of data security within the cloud is the top concern and the pivotal factor in its widespread use and acceptance. Data security in clinical operations has legal, regulatory, and competitive implications, so it must be robust, comprehensive, and reliable. Furthermore, in this industry, it must support compliance with the Food and Drug Administration's (FDA) 21 Code of Federal Regulations (CFR) Part 11, the Electronic Records; Electronic Signatures rule that requires computer systems and controls be available for FDA inspection.

  At the time of this writing, the FDA is in the early stages of developing a roadmap to explore areas where cloud computing may be effectively used.  

Understandably, stakeholders looking to transition data to the cloud are seriously focused on the safety of their data and complying with regulatory mandates, even those yet to be defined. As there are no uniform data security standards, stakeholders considering outsourcing this function must find cloud technology providers who are sensitive to factors unique to the life sciences industry and adopt the highest level of security. Six key elements that should be considered when evaluating cloud-based solutions providers, such as those offering SaaS, are outlined in Figure 3, and are described in more detail below.

Figure 3. Key security elements that should be considered when evaluating cloud-based providers. 

Application refers to the fact that when working in the cloud, the need for security starts immediately, as soon as users log on. It is the responsibility of the vendor to offer strong authentication and authorization systems. Authentication ensures that only those with valid user credentials obtain access to the application. Authorization entails controlling which services and data items users may access. As applications expand within the cloud, administrators decide which users are permitted to see and update them based upon defined parameters.  

Additional security around applications includes: 

All application-level access should be protected using strong encryption to prevent unauthorized snooping of online activities. 

Application data must be validated on the way in and on the way out to ensure security. 

Robust watermarking features ensure that materials cannot be reproduced or disseminated without permission. 

Controls enforce who can print, copy, or forward data, and prevent such activity unless it is specifically authorized. 

Rigorous security checks to ensure data security and prevent breaches due to security vulnerabilities in the application are a must. While data are in use, all files should be encrypted, including electronically distributed copies, and no clear text versions should remain on end-user computers. Some advanced security features that a number of cloud providers may offer include real-time reports and user activity audit trails to track who is looking at what data, when information was accessed, and what changes, if any, were made to the data as a result of that access. Best-in-class vendors will ensure that sensitive data that are backed up to facilitate quick recovery in case of disaster are protected by strong encryption schemes to prevent accidental leakage. 

Security for a redundant infrastructure is essential to provide uninterruptible service. Best practices for cloud technology providers include using real-time replication, multiple connections, alternate power sources, and state-of-the-art emergency response systems to provide thorough data protection.  

Process security is a function that qualified cloud technology vendors take very seriously to ensure thorough reviews of their security policies and procedures. As a best practice, they should consider earning SAS 70 Type II certification from the American Institute of Certified Public Accountants or international equivalents.

  SAS 70 certification is an internationally recognized auditing standard, and Type II refers to an independent audit of a company's procedures, policies, and controls to verify and validate that the organization is actually following them. Another recognized measure of risk management strategies is the ISO-27001 certification, an Information Security Management System (ISMS) standard.

  The objective of this standard is to provide a model for establishing, implementing, operating, maintaining, and improving an ISMS. 

Vendor personnel are a critical component of any information system, but they can also present insider threats by malicious employees that no outside attacker can match. At the vendor level, background checks of all employees and enforceable confidentiality agreements should be mandatory, and administrative controls should be in place to limit employee access to client information. Ideally, all employees with access to sensitive information should be tested, and possibly even certified, before interacting with clients. In addition, the best vendors ensure that their employees are kept current by providing ongoing training and certification retesting to verify that skills and knowledge remain sufficient.  

Product development security can be overlooked if the outsourced provider is rushing to meet deadlines for a new market release. This can result in software with bugs that make it prone to security vulnerabilities. As a best practice, the cloud technology vendors should use a Security Development Lifecycle (SDL) process for developing and deploying applications. SDL refers to making certain that each phase of development—architecture, design, coding—has a security review, resulting in faster identification of security issues before a new product or upgrade is released. 

As life sciences companies consider moving functions into the cloud to expedite aspects of clinical trial operations, they are likely to evaluate the process changes needed to implement this step. They will also be considering whether to build capability in-house or outsource to a cloud-computing vendor.   

Making this decision forces companies to address the reality that developing and administering a comprehensive and secure cloud-based system in-house requires a major time and resource commitment. Not only would in-house IT professionals be responsible for procuring the hardware for a data center, installing and validating it, and managing ongoing software updates, they would also have to develop, oversee, and maintain a large security system. Furthermore, an in-house system would require ongoing support for investigative sites around the world that are using the platform. Large biopharmaceutical companies might have relationships with many thousands of sites, meaning that responsibility for supporting this many end-users is a very tall order. They would have to manage thousands of active end-user credentials, and provide a 24/7/365 multi-lingual help desk to assist sites across the globe with issues such as forgotten passwords, or how to perform specific functions within the platform.  

By comparison, opting for a hosted solution requires no upfront capital investment and relieves companies of the burden of managing, maintaining, and supporting it. With the data security checkpoints described earlier (Figure 3), and with global around-the-clock end-user support, internal IT resources are freed up for other purposes. Furthermore, the best vendors are staffed to scale-up quickly, so adding studies and investigative sites is simple and fast.  

A comparison of outsourcing to a hosted provider vs. building in-house capability appears in Table 1.

Table 1. Outsourcing to a SaaS provider offers significant economic and time savings. 

In a recent study by the Pew Internet and American Life Project, 895 technology stakeholders were questioned on their expectations for growth in cloud computing.

 Nearly three-quarters of respondents—71 percent—believe that by 2020, the cloud will dominate information transactions. According to the survey, this is due to the distinct advantages offered by the cloud, such as easy, instant, and individualized access to tools and information consumers need wherever they are, using any networked device.  

This is a generalized expectation of the cloud, but industries that are highly regulated, such as life sciences, financial services, and telecommunications have complex security concerns that may limit its growth in comparison to other industries. As data security issues are hammered out, however, cloud computing holds a great deal of promise for the life sciences sector. 

Throughout the clinical development continuum, from R&D to the pre-clinical phase to clinical trial work and beyond, the volumes of data being generated must be analyzed and stored in accordance with corporate directives to improve time- and cost-efficiencies. The cloud offers this option. Not only can the cloud eliminate the inefficiencies and costs associated with traditionally paper-based manual processes, it can also add a layer of security and control that is simply not possible with paper. Introducing these critical efficiencies into routine processes helps companies adhere to increasingly aggressive timelines, and comply with changing global regulations in a timely manner. And importantly, with the cloud, there is the promise of reining in IT expenditures by no longer having to procure, maintain, and update the system or support all end-users.   

Over the next few years, the industry will watch with keen interest as the transition to the cloud unfolds. Companies will work through their decisions to enter various applications into the cloud, and during this process, they will be evaluating whether this work will be done internally or with outsourced cloud technology vendors. In an effort to toe the line on infrastructure costs and limit strain on internal resources while raising the bar on data security, outsourcing becomes a compelling option.  

is Vice President of Life Sciences Product Marketing at IntraLinks, 150 East 42nd Street, 8th Floor, New York, NY, e-mail: 

What cloud computing is, why it can save time and money, and how to select the right cloud solution.

Cloud Computing Efficiency

Author Gerald Van Roey has over 10 years of experience as a clinical monitor. His book offers sharp insights for both the new and experienced monitor. 

After the first chapter primer about clinical research, Van Roey delves into the more granular areas of the practice of clinical monitoring. For that, the best chapter is Chapter 2. It looks at the qualities that make a good monitor and the relationship with an investigator.  

Chapter 7 offers the reader a good grasp of initiation visits and tips on how to approach the study personnel.  

Chapter 8, titled Monitoring Visits, is a large part of the book and takes on a lot. There is discussion about the import and export of clinical supplies, IMP distribution, tracking, and return of used IMP, which is very interesting and something with which I didn't have a lot of knowledge, and found very helpful. 

Sections on site management, recruitment issues, the right protocol, and site selection included good information, but maybe not so related to the function of monitoring. Subject recruitment is a very complex area of clinical trials. It requires many initiatives that all fire on the same cylinders to ensure rapid and inclusive enrollment. The chapter offers several good ideas such as the monitor playing a part in communicating protocol information to the site, pinpointing problem areas, and suggesting solutions. But the section seems geared to the pharmaceutical company, or the CROs function.  

Overall, the book is well written, with a pleasing design. It offers excellent tips, drawing these out in colored boxes to help the reader. 

The book is available from the publisher PharmImage, 

, and costs €39.95, or approximately $56. 

News

Our book review for the latest industry guidebook for monitors.

Best Practice for Clinical Monitoring

Getting Personal Over Personalized Medicine

Opportunities for Personalized Medicine in Cancer Trials

Personalized medicine is the tailoring of medical treatment to a specific subset of patients who are usually identified by genetic markers or other molecular profiling strategies. There is an increasing interest in this therapeutic strategy on the part of pharmaceutical and bio-pharmaceutical companies, consumers, and third-party payers. Consequently, the level of clinical trial activity surrounding personalized medicines is intensifying as sponsors seek ways to target their therapies to patient populations that would most benefit from them. The personalized medicine landscape, however, is still evolving. While some pharmaceutical and biotechnology companies are currently exploring this field, others may lack the expertise or the inclination to do so. Fortunately, clinical research organizations (CROs) can provide valuable assistance in this area. This article will discuss the rationale and scientific basis for personalized medicine, while also providing an overview of some of the services CROs can provide in assisting sponsors of personalized medicine clinical trials.  

The growing interest in personalized medicine has been driven by major advancements over the past decade or so in genomics (including toxicogenomics), proteomics, imaging, and diagnostics (predictive/prognostic testing).  These advances have spurred efforts within pharmaceutical and biotechnology companies to prospectively identify and develop medicines that are designed to work in individual patients based on their genetic makeup and the specific molecular characteristics of their disease. 

Expanded efforts to develop medicines aimed at discrete groups of patients appear to be particularly timely, given that an estimated 55 percent of drugs consumed in the United States—including as many as 80 percent of approved anticancer therapies—are thought to be ineffective in the patients who receive them.

  The estimated annual cost for such unwarranted or "wasted" care ranges from $250 billion to $325 billion.

The personalization of therapeutics is being driven by an enhanced understanding of how human genetic variation affects an individual's response to treatment. As described in a recent report from Business Insights Ltd.,

  this understanding largely results from the advent of sophisticated genomics capabilities and the expanding use of biobanks that allow researchers to link data from genetic studies to disease outcomes. Recent advances in genomics have facilitated the development of predictive tests that stratify patients by response to therapy, usually by identifying patients who have the best chance to benefit from a particular treatment or who may be prone to particularly toxic effects of a treatment. An example of the former is the human epidermal growth factor receptor-2 (HER2) gene, which is amplified in roughly 25 percent of breast cancers and predicts a particularly poor prognosis in untreated patients. By developing predictive testing for HER2, scientists can identify patients who are most likely to respond to targeted therapy. Predictive testing for HER2 led to development of Genentech's Herceptin® (trastuzumab), a monoclonal antibody targeted specifically to breast cancer cells that overexpress HER2, but which does not produce a response in tumors that do not overexpress HER2. Predictive tests for additional genetic biomarkers (e.g., BCR/ABL tyrosine kinase, PML/RAR alpha fusion protein, and EGFR/KRAS) have been similarly co-developed with other targeted anticancer therapies, such as Novartis' Gleevec® (imatinib mesylate), Bristol-Myers Squibb's Sprycel® (dasatinib), Cephalon's Trisenox® (arsenic trioxide), AstraZeneca's Iressa® (gefitinib), ImClone's Erbitux® (cetuximab), and Amgen's Vectibix® (panitumumab). 

Another application of personalized medicine is the development of prognostic tests that stratify patients by disease outcome to guide clinical decision-making. As with predictive tests, the use of prognostic tests has thus far been mostly limited to the oncology setting. Recent examples include Genomic Health's Oncotype DX® 21-gene breast cancer assay and Agendia's MammaPrint® assay, both of which predict the risk of disease recurrence in certain women with early-stage, node-negative breast cancer.

Advances in genomics have also given rise to toxicogenomic testing, which identifies patients who may experience treatment-related adverse events due to hypersensitivity reactions or variations in metabolism. Myriad Genetics' TheraGuide® 5-FU test, which predicts toxicity to the chemotherapeutic agents fluorouracil and capecitabine, is a notable example in oncology.

  Toxicogenomic information can also inform clinical decision-making in other disease areas. For example, patients with glucose-6-phosphate dehydrogenase deficiency are at an elevated risk of toxicity and can be counseled to avoid anti-malarial drugs, certain analgesics, and some non-sulfa antibiotics.

  Another example is that of irinotecan (Camptosar®, Pfizer) and the UGT1A1*28 allele. Patients who are homozygous for this allele are at increased risk for neutropenia.  

In some cases, pharmacogenetic or toxicogenomic information is incorporated into product labeling, as has been done recently for Bristol-Myers Squibb/Sanofi Pharmaceuticals partnership's Plavix® (clopidogrel), the label of which warns of an increased risk of cardiovascular events in patients who have mutations in CYP2C19, the enzyme that converts Plavix into its active metabolite.

  Tests are now available to determine a patient's CYP2C19 genotype and to directly assess platelet function in treated patients.

Despite the early successes of personalized medicine, its incorporation into routine clinical practice has been slow, and its scientific basis does not currently impact the care of the vast majority of patients. The adoption of personalized medicine has been hampered by the lack of reimbursement for many genomic-based tests, the dearth of targeted therapies in companies' development pipelines, and few examples of clinical benefit from identification of novel biomarkers.

  Proponents of personalized medicine would thus do well to demonstrate its promise in terms of return on investment (ROI).

  Consumers can theoretically reap an almost immediate ROI in personalized medicine due to a decrease in adverse events (based on avoidance of unnecessary treatment) and the potential for enhanced therapeutic response. Although consumers may end up paying more for personalized treatments in the short term, they may enjoy a longer-term benefit based upon improved quality of life and decreased mortality. For biotechnology companies, it is likely that continued advances in personalized medicine will shift the industry paradigm away from blockbuster products to one of "more therapies, smaller markets." Companies that enter the personalized medicines market early can potentially earn significant ROI as traditional therapies are replaced by highly effective targeted treatments. Companies can also increase their ROI through enhanced patient recruitment and streamlined R&D processes that make drug development less costly, in particular by shortening the time to drug approval. Application of the principles of personalized medicine may be particularly valuable in early-phase drug development, as it can allow companies to more quickly identify whether a drug will or will not work in certain populations (e.g., proof of concept studies), thereby facilitating later-stage "go/no-go" decisions. On the other hand, companies that are slower to adopt personalized medicine may find it more difficult to gain share when they do enter the market. While some companies may not feel there are adequate returns to pursue personalized medicine, choosing instead to focus on more broadly targeted therapies, they may miss the opportunity to increase their potential patient base by developing a suite of personalized medicines with enhanced efficacy, safety, and adherence. 

Signaling its support of the concept of personalized medicine, the US government has made development and use of personalized medicine a high priority in its efforts to reform the nation's healthcare system and reduce healthcare-related costs. In a recent commentary in 

 FDA Commissioner Margaret A. Hamburg and National Institutes of Health Director Francis S. Collins describe how their respective institutions are working together to "develop a more integrated pathway that connects all the steps between the identification of a potential therapeutic target and the approval of a therapy for clinical use." They liken these efforts to building "a national highway system for personalized medicine, with substantial investments in infrastructure and standards."  

To use Hamburg and Collins's metaphor, the personalized medicine highway is still under construction. As noted at the beginning of this article, while some biopharmaceutical companies may be inclined to explore it, navigating the highway remains a significant challenge for many. That is largely due to the lack of adequately designed studies to assess the clinical utility of genomic testing and other personalized approaches.

  Fortunately, CROs are well-equipped to provide sponsors with a viable navigation system for the design, conduct, and coordination of personalized medicine clinical trials.  

For pharmaceutical and biotechnology companies, outsourcing clinical trials to CROs can yield significant financial and human resource benefits. According to the Tufts Center for the Study of Drug Development, working with CROs has enabled companies to keep R&D head counts stable over the last decade even as the number of active clinical projects around the world increased by 80 percent. Moreover, trials managed by CROs are, on average, completed 30 percent sooner than those conducted in-house, providing an average time-savings of four to five months.

Specifically, CROs offer a variety of services that may benefit companies developing personalized medicines. Although some or all of these services can be provided by the sponsoring companies themselves, many sponsors recognize that their core competencies lie elsewhere and choose to delegate these responsibilities to organizations that specialize in the processes and logistics of managing clinical trials: 

 A number of CROs employ physicians and statisticians with extensive experience in protocol design, including knowledge of genomic tests and expertise in adaptive study design and related strategies that may be important in the design and interpretation of specialized trials of personalized medicines. 

 Difficulties in patient enrollment contribute to delays in most clinical trials, thereby increasing trial costs. CROs, with their access to investigator and, in some instances patient databases, can use analytic techniques to screen large numbers of electronic records to help sponsors identify potential candidates for personalized therapies, based on certain diagnostic criteria. Such capabilities can expedite trial initiation and reduce the costs of patient recruitment. In a recent survey of 84 sponsor companies, Cutting Edge Information concluded that CROs can determine the likelihood of strong recruitment by using tools such as dedicated patient recruitment groups and databases with site-specific demographic information.

 Some CROs can provide assistance in identifying and validating biomarkers that are correlated with therapeutic response, resistance, and toxicity. This knowledge can be leveraged in both preclinical and clinical testing of drug candidates. 

The Accumetrics VerifyNow®  test for platelet function

  is an example of a diagnostic test that can be paired with a specific agent. Many CROs have experience in and can assist companies in designing and executing trials for diagnostic tests that are being developed along with drug compounds.  

 Regulations that address the testing and eventual approval of personalized medicine have lagged behind the rapidly developing science.  The co-development of companion diagnostics and the use of biomarkers in early and perhaps later-phase testing are examples of topics that should be addressed with the FDA and other regulatory agencies. In addition, and under circumstances defined by FDA, the agency is open to receiving and discussing pharmacogenomic information as it may relate to a drug under development separate from the product review process itself. A number of CROs have sophisticated regulatory affairs departments that can facilitate productive interactions between sponsors and government agencies on various topics, including the evolving personalized medicine landscape. 

 With their ties to experts in a wide range of medical and scientific disciplines, CROs can facilitate assembly of DMCs, provide guidance on the development of DMC charters, and provide unblinded staff support to these committees. 

 Biobanks, which collect and store human biospecimens (e.g., whole organs, tissue, blood, plasma, and urine, as well as DNA and RNA), play an important role in personalized medicine, as they facilitate testing of medicinal compounds on preserved samples. Not many small pharmaceutical or biotech companies have their own biobanks. Furthermore, storage of biologic samples is deceivingly complex and must take into account the collection, transportation, storage (under a variety of different and tightly monitored thermal conditions), and reliable retrieval of such samples. Some full-service CROs and a number of stand-alone facilities can provide this critical service.  

While CROs can offer the above array of services a la carte to clients or integrate them for individual trials, many national and international CROs are well-positioned to provide these services as an integrated package for an entire development program. Combining regulatory and medical/scientific expertise and follow-through and having a single dataset can be a big advantage to expediting a development program. Securing the services of a single CRO for the entire development program can also foster more expeditious biomarker identification/validation and diagnostic testing co-development, which generally occur throughout the development program. 

Furthermore, CROs, with their broad clinical and regulatory development experience and expertise across numerous therapeutic areas, are in an excellent position to offer strategic regulatory and clinical program development advice at the earliest stages of development planning. This process could begin as early as the IND-consideration stage. 

There are many CROs and identifying the right one can be a challenge for sponsors. CROs are generally classified by size, national/international, therapeutic focus, and overall capabilities. Most large CROs offer a broad array of therapeutic expertise and are full-service as well as international in operations. These CROs can often provide the best "one-stop shopping," especially for consideration of full development program outsourcing. CROs, in general, are always willing to provide potential clients with a capability presentation at no cost to the sponsor and to provide proposals/bids for solicited work. Choosing the right CRO then becomes a matter of personal preference, comfort "fit," CRO capabilities/history, and cost. 

The promise of personalized medicine can potentially open up vast horizons for patients and industry alike. By providing their specialized expertise in conducting clinical trials, as well as critical expertise throughout all stages of the drug development process, CROs can help developers of personalized medicines, and the patients who would benefit from them, reach these goals. 

As the popularity of personalized medicine grows the role of the CRO continues to evolve.

Applied Clinical Trials-07-01-2011

Applied Clinical Trials Digital Edition - July 2011

Recruiting Diabetes Subjects

Eyes Play a Focal Role in Research

Fighting for Territory and Funding in Europe

Cloud Computing Efficiency

Best Practice for Clinical Monitoring

Personalized Medicine Development

Italian Regulator Prepares for Europe's Top Job

Value of Time and Money

Transforming R&D Through Open Innovation

Biosimilars Development Raises Research Questions

Protecting the Vulnerable in India

Business and News Update July 2011