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In a new report titled "Advocacy Groups: Enhancing Relationships and Patient Recruitment," Industry Standard Research interviewed 10 prominent patient advocacy groups to profile their involvement in clinical trials. All advocacy groups recognize clinical trials as a critical component of advancing knowledge. However, the degree of focus on educating patients about clinical trials and promoting participation in trials varies widely among organizations.  

The organizations with a higher focus on clinical trials are the most involved in the clinical trial design process, frequently emphasizing the importance of patient relationships with industry, educating patients about trials, and partnering with pharma on trial-related endeavors.  

Figure 1. Spectrum of clinical trial focus among advocacy groups.			

Groups with a lower focus on clinical trials are not involved with the design of industry trials and do not have established processes to reach out to patients regarding trial education (general or related to specific trials). This is not to say that organizations not at the "high" end of the spectrum do not care about clinical trials. They do. They just have barriers to implementing a process encouraging patients to join industry's clinical trials that they have either been unable to or unwilling to cross.  

Relationships Between Advocacy Groups and Pharma

Autumn is the time for reflection in Europe. The heady days of summer are over, and the resumption of political and business activity provokes re-evaluations of achievements to date, and of what might be the way ahead.  

For health policy in Europe, this autumn is particularly pregnant with assessments and plans—and the nature of the discussions underway prompts the question as to just how much Europe cares about clinical trials in a changing world. The narrative behind European health policy is undergoing a profound change—and the result doesn't seem to leave a lot of room for clinical trials. 

Take the discourse of Zsuzsanna Jakab, WHO Regional Director for Europe, and a key influence on the way European governments perceive the healthcare challenge. During September she delivered a lengthy update of WHO thinking about Europe, based largely on a strategy adopted last year, known as Health 2020. This envisages governments linking policies, investments, and services in health policy—and focusing on reducing inequalities. "Political commitment to this process is essential," she said, insisting on the need for "common purpose and broad collaborative effort by people and organizations across society in every country: governments, nongovernmental organizations, civil society, the private sector, science and academia, and health professionals." 

For Jakab, Europe is on the brink of a "brave new world," in which good health is recognized as essential for economic and social development, and now features prominently on the political and social agenda. But it is hard to see just where health professionals in the clinical trials community could fit into the picture she paints. Jakab, like a growing number of politicians and senior officials in Europe, is acutely conscious of the challenges in healthcare, and her recommendations do not put much emphasis on Europe medicating its way out of trouble. "Governments may feel daunted by growing health expenditure. The development and introduction of expensive medical technologies and treatments drive up the cost of managing chronic diseases and multiple morbidities," she remarks. 

Her conclusion is that these cost pressures "provide a strong economic case for moving upstream to promote health and prevent disease". Action promoting health and well-being, along with effective preventive measures within and beyond the healthcare sector, "could prevent a tangible share of the burden of disease and of the economic costs associated with it," she emphasizes. In the longer term, non-communicable diseases can be tackled cost-effectively through changed behavior and lifestyle. Depression, for instance, can be prevented by "early action in childhood to strengthen social and emotional learning, coping skills, and improved bonds between parents and children"—but not a word about psychotropics. Her emphasis in health policy is on nutrition, on prevention of motoring accidents, and of tackling environmental chemical hazards. 

But many countries are not reacting fast enough to these possibilities, says Jakab. Budgets and policies lack either a health or equity focus, she laments, and only 3% of health expenditure is committed to these upstream programs. "In this brave new world, all this simply has to change," she declares. 

Jakab is not alone in her view. The current president of the European Union's health council performed variations on the same theme in September too. Vytenis Povilas Andriukaitis, Lithuania's Minister of Health, made clear the main priority of his country's turn in the EU chair—which lasts until the end of this year—is "modern, accessible, and sustainable health systems." Elaborating on just what that means, he spoke at length about "measuring and monitoring the effectiveness of investments in health." This is not good news for healthcare industries that depend on the successful development and launch of products designed for treatment. As prevention and lifestyle adaptation become increasingly important for policymakers, the merits of intensive (and expensive) work on bringing new medicines from concept to clinic inevitably pale by comparison—and the risk grows that the money and support will follow the political bandwagon.  

The economic crisis is one of the factors behind the closer attention to efficiency of health spending, and is seen by many EU officials and politicians as an opportunity for deep change in restructuring healthcare services. A major EU-wide review this year of economic growth prospects recommended reforming health systems to ensure their cost-effectiveness and sustainability, and a re-assessment of how efficiently they perform in using of public resources. The guidance came from the European Union's economic and financial affairs council. It was the culmination of a six-month exercise in checking national spending plans to make sure that they meet the objectives of European economic recovery. 

The so-called "guidance" included tough instructions to European countries to get a grip on health spending—with specific criticisms levelled at the way some of them are managing pharmaceutical spending. The nature of the guidance—backed by EU leaders at their June summit, and which is, in effect, binding—marks a new phase in the European Union's gradual assertion of powers over national health spending. France was told that medium and long-term public health expenditure was set to increase, requiring "greater scrutiny and efficiency, in particular in pharmaceutical spending." Germany "has made only limited efforts to improve the efficiency of public spending on healthcare," and "past reform efforts in the health sector as well as this year's reform of long-term care appear insufficient to contain expected future cost increases." The recommendations for Germany in 2013-2014 include "a stronger focus on prevention." Belgium was also told to explore "improved cost-efficiency of public spending on long-term care services and cost-saving measures of health prevention." And on-going reform of health services in Finland must be geared to "deliver productivity gains and cost savings" in the provision of services. 

Against this somber background of cost containment and an incipient shift from treatment to prevention, what factors still militate in support of clinical trials? Center-stage, of course, is the current discussion of an update of the European Union's rules on clinical trials—but this is still stuck in discussions among EU governments, many of which are resistant to what they see as infringement of their own autonomy in a bid to streamline trial authorization. The vigor of the clinical trials industry in Europe has won recognition from many EU officials and politicians—particularly attractive at a time when Europe is desperate to find ways of asserting and retaining its superiority in high-tech sectors as its overall competitiveness comes under increasing threat in a globalized economy. But no revision of the EU rules—and still less the revision currently under discussion—is of itself going to be enough to guarantee continued success. 

Other pressures also offer some succor to the beleaguered sector. The growing push from academics, physicians, and industry for recognition of the special case of personalized medicine inevitably puts clinical trials—albeit modified forms of clinical trials—in the spotlight. At the senior EU level there is also lip-service paid to the prospects that personalized medicine can offer, both for healthcare and as a potential contributor to Europe's global competitiveness. But so far the thinking about what could be achieved in this complex field remains inchoate—and the ideas about how clinical trials should be promoted remain confused.  

For years the EU has been straining to deliver a strategy paper on how 'omics could contribute to personalized medicine—and how trials could be adapted. But it has still not completed its reflections—and all the latest draft is able to offer on clinical trials are vague ideas like the following: "A range of new more flexible alternative designs, statistical methods, and analysis tools need to be considered, (e.g., adaptive trial designs, computationally, and logistically complex), and which need intensive modelling and simulation, enrichment designs when sound biomarkers can accelerate the clinical development of 'personalized' medicines meant to address unmet needs." 

Meanwhile, a broadly-based European alliance to promote personalized medicines has released its own view of the way ahead—which notes that "the classical approach to clinical trials cannot capture the necessary data adequately." Now that subgroups of patients can be identified within a broad disease category via prognostic or predictive biomarkers, "these scientific advances in diagnostic refinement and stratification have to be incorporated into the format of clinical trials"—which means that the legal framework in Europe needs adapting, not only to permit easier access to smaller groups of subjects, but also to recognize the validity of results from trials much smaller than the classic randomized approach.  

At the European Medicines Agency too, support is growing for adaptive licensing methods that will be based on a new paradigm for clinical trials. In the European Parliament in late September, Francesco Pignati of the European Medicines Agency highlighted the gap often observed between efficacy as demonstrated by clinical trials, and effectiveness when a medicine is used in clinical practice. Acknowledging the work of EMA colleague Hans-Georg Eichler, who has been one of the leading exponents of modifying drug registration rules to reflect more accurately the state of knowledge of a medicine at any given time, Pignati said flexibility was urgently needed to overcome the knowledge gaps. 

But so far, it must be said, the arguments for greater attention to clinical trials are less developed, and less trenchant, than the calls from the big battalions of economic affairs ministers and health campaigners for a step away from medicines development and several steps toward preventive medicine. Will the clinical trials community muster their arguments more strongly? And will they do it in time? 

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

View from Brussels

Will the clinical trials community assemble their arguments, and will they do it in time?

Does European Policy Still Have Room for Clinical Trials?

Patient recruitment and retention are among the greatest challenges facing the clinical research enterprise today and are a major cause of drug development delays. New research from the Tufts Center for the Study of Drug Development (CSDD) found that while nine out of 10 clinical trials worldwide met their patient enrollment goals, drug developers typically had to nearly double their original timelines to achieve the targeted numbers. 

A formidable obstacle to timely and effective patient recruitment is the public's lack of knowledge about the clinical research process, particularly since improvement in knowledge is associated with greater willingness to participate in trials. One National Institutes of Health study of more than 1,000 US adults found that only one in three had even heard of clinical trials. 

Despite the high costs of drug delays, the pharmaceutical industry has not been particularly proactive in its efforts to bridge this awareness gap. Nor has it been particularly innovative in its patient recruitment methods. According to the results of a recent Tufts CSDD study, most drug sponsors and contract research organizations rely on a limited number of traditional recruitment and retention tactics, such as physician referrals and newspaper, television, and radio ads, and non-traditional approaches.  

A case in point is the fact that the industry has largely ignored the more than 60,000 pharmacies in the United States as a potential channel to educate and engage the public about clinical research. The Center for Information and Study on Clinical Research Participation (CISCRP) has now conducted two studies to examine the feasibility of pharmacy-directed outreach and education. Our findings indicate that the industry has an opportunity to leverage pharmacists as an untapped, trusted source to deliver clinical research education, raise public awareness, and facilitate timely patient recruitment.  

Educational channels offering trust and accessibility

The vast majority of the general public is unfamiliar with and wary about clinical research. CISCRP research has found that fewer than one in 20 Americans know where to find information about relevant clinical trials. Moreover, the role of mistrust as a barrier to clinical trial participation has been widely reported in the literature. In a 2012 Harris poll, only 12% of Americans indicated that pharmaceutical companies are "generally honest and trustworthy."  

Conversely, major international opinion polls indicate that pharmacists are one of the most trusted sources for health-related information. In Gallup's 2011 Honesty and Ethics survey covering 21 professions, pharmacists ranked second only to nurses and ahead of physicians—the ninth consecutive year they ranked in the top three. 

Pharmacists are also the most accessible health information providers in the country. Americans visit pharmacies at more than five times the annual rate at which they visit their primary and specialty care physicians combined. These pharmacist-patient interactions are likely to increase as pharmacists become more involved in patient care, including their expanded roles in managing medication therapies and chronic diseases. 

Feasibility and viability of pharmacists as educators

Since pharmacists are highly trusted and have plentiful opportunities for patient interactions, CISCRP conducted research to examine whether they might be an effective channel to educate and engage the public about clinical research. Our first study in 2010 focused on potential public receptivity to receiving information on clinical research from pharmacists. Its notable findings included: 									

Nearly 80% of the 2,650 respondents would like their pharmacists to tell them about clinical trials, yet only 1% reported receiving this information from their pharmacists.

While all demographic groups were open to receiving pharmacy-directed clinical research educational materials, respondents who had closer relationships with their pharmacist were the most receptive.

Respondents were most interested in information about how to find clinical trials, whether they are safe, and how to learn more about them.

Our follow-up study in 2012 evaluated the impact of in-pharmacy education on patient's knowledge, interest, and willingness to participate in clinical trials. CISCRP collaborated with McKesson to engage and train pharmacists at 32 locations within its national network of independent community pharmacies. CISCRP provided each pharmacy with educational materials to display and/or distribute for a period of two to three months. Pre- and post-surveys among 487 patients were conducted to gather baseline measures and to assess the impact of educational materials and in-pharmacy discussions.  

The results indicated that outreach through the pharmacy educational channel markedly improved patients' knowledge of and interest in participating in clinical trials. Here a few highlights: 					

Nearly all baseline measures of awareness and comprehension increased by 10 to 20 percentage points, including patient confidence in their knowledge about clinical research and in their understanding of the benefits and risks of participation. 

Six out of 10 respondents in the post-test also reported that they would be more likely—"very" and "somewhat"—to recommend clinical trial participation to a friend or family member. 

Although the study objective was to measure receptivity and changes in comprehension, not behavioral changes, we were surprised to find that nearly six of the post-survey respondents (4% of the total) enrolled in clinical studies during the limited timeframe of the study.

The study also corroborated other research regarding pharmacists' accessibility and trustworthiness. More than 30% of patients reported visiting their pharmacies six or more times during the period when the educational materials were on display. And 15% indicated that they had spoken to the pharmacist or pharmacy staff about clinical trials. 

This research suggests that pharmacies represent a compelling new patient outreach and education opportunity. Moreover, given their accessibility and closeness to patients, pharmacists may play a valuable role in disseminating information supporting sponsor and CRO patient recruitment strategies. Specifically, pharmacists may add value to targeting prospective study volunteers by vetting and validating pre-qualified candidates based on the pharmacists' personal knowledge of patients and their healthcare options.  

As this communication channel begins to take root, it will be important to provide general education about clinical research to pharmacists and to introduce them to good clinical practice concepts. 

Community pharmacists provide a potential channel for difficult-to-reach individuals in remote areas, a largely untapped target demographic. These potential trial participants generally visit their pharmacies much more often than their city and suburban counterparts, which affords study sponsors more opportunities for education and engagement. Many of the pharmacists in our second study were located in relatively remote areas; one commented that "This was a new experience for patients living in our small town. Usually only large cities or large hospitals have access to this kind of information."  

The clinical research enterprise has a critical and growing need to engage the public and patients in discourse as to the nature, safety, and importance of clinical research in advancing medical knowledge about disease and how to treat it. As our study results demonstrate, pharmacists are an important new channel for increasing clinical research literacy among patient communities and for raising patient awareness about opportunities to participate in clinical trials. 

Founder and Chairman of CISCRP. Director, Sponsored Research Programs at Tufts CSDD, e-mail: 

Feature Article

Results show pharmacists are an important vehicle for increasing clinical research literacy.

Leveraging Pharmacists as a Channel to Raise Clinical Research Literacy Among Patient Communities

CTI Clinical Trial and Consulting Services 

(Cincinnati, OH) announced the following new hires: 

, RN, Associate Director, Clinical Trials; 

, RN, BSN, Assistant Director, Medical and Scientific Affairs; and 

, CPA, as Director, International Accounting and Finance. The following promotions were also announced: 

 to Senior Business Development Associate; 

 to Associate Director, Clinical Operations Study Management; and 

 (Reston, VA) announced the appointment of 

to the role of President of Trio Clinical Resourcing, an Aptiv Solutions subsidiary devoted to clinical and regulatory staffing. Aptiv also announced their Senior Vice President of Software Development and Consulting, 

, PhD, was elected as a Fellow of the American Statistical Association, the world's largest community of statisticians.  

 (Zug, Switzerland) announced their expansion to India, and the appointment of 

, MD, as Regional Director for India and the Asia-Pacific region.  

(Rochester, NY) announced the addition of 

, MD, as Director of Anatomic Pathology. 

has assumed the role of General Manager for its Rockford, IL based facilities. PCI operates nine facilities in Rockford, totaling over one million square feet and employing over 1,300 associates.  

(Research Triangle Park, NC) announced three senior executives have assumed new leadership roles within the organization. 

 has been named Vice President, Oncology Clinical Development; 

 has been promoted to Global Head of Regulatory Affairs; and 

has been named Vice President, Global Quality and Compliance. 

 as a non-executive director. Powell is the founder and Chairman of MyMeds&Me Ltd., a company focused on the capture and processing of adverse events and product complains, and Chairman of CISIV Ltd, an organization specializing in the capture and processing of real world life sciences data. 

 in the new role of President of Catalent Asia Pacific.  

 (Burlington, MA) announced the creation of two new positions to lead its growing business in Europe and Asia. 

 will take on the new position of President of inVentiv Health Europe. 

 will join the company as Executive Vice President for Asia.  

(King of Prussia, PA) promoted UK researcher 

 to head its biopharmaceutical franchise in respiratory. As Executive Director of Biopharmaceutical Development, Respiratory, Lake will be responsible for senior oversight on major projects as well as building Theorem's respiratory business globally. Theorem also announced 

 has been named Vice President of Biopharmaceutical Development for the Infectious Disease franchise.  

Association of Clinical Research Professionals (ACRP)

 (Alexandria, VA) announced the hiring of 

, RN, BScN, MBA, CCRC, to serve in a new position as Deputy Executive Director for the association. 

 (Philadelphia, PA) announced an additional expansion of its executive management team. It has appointed 

 as Executive Vice President and Chief Commercial Officer.  

Pharmaceutical Product Development, LLC (PPD)

 (Wilmington, NC) announced it has appointed 

, MD, as Vice President of Global Product Development.  

. They are welcomed aboard CATO's international commercial team. 

(Exton, PA) announced two senior-level appointments to lead its consulting service expansion in regulatory affairs and drug development strategies. 

, PhD, was named Vice President of Regulatory Affairs. 

, PhD, was named Vice President, Pharmaceutical Development Consulting Services. 

 has been appointed to the position of Vice President, Regulatory and Scientific Services. 

 (Rochester, NY) announced that it has joined forces with the 

as a Global Impact Partner. The Global Impact Partners are a group of research professionals and industry providers who will work together to address the most pressing issues facing sites today, in addition to any future problems and trends.  

(Madison, WI) announced a two-year partnership with the 

, a trade organization that represents global clinical research sites.   

(Raleigh, NC) a global technology and eclinical commerce network for clinical trials announced that it has formed a strategic partnership with 

 announced that the IRB Services team has selected Intralinks VIA to support all of its secure beyond-the-firewall collaboration needs. 

(King of Prussia, PA) announced the formation of a strategic alliance with 

that will provide clients with an integrated solution from nonclinical testing and analysis through clinical development and registration. 

(Minnetonka, MN) a global life sciences technology company specializing in clinical study management systems, announced that 

, a, full-service clinical research organization focused in early phase oncology, vaccines, and general medicine development, has joined the iMedNet Partner Program.  

 (San Francisco, CA) announced that partner company 

. won Frost & Sullivan's North American Product Leadership Award for pioneering electronic informed consent for clinical trials. Frost & Sullivan, a respected global research organization that tracks more than 250,000 companies, compared Mytrus to key competitors in a rigorous review and named Mytrus winner of the North American Product Leadership Award in Clinical Trials. 

(Cincinnati, OH) was awarded the 2013 Goering Center Private Business Award. The Goering Center recognized finalists and category winners for their success in family and private business.  An independent panel of judges, comprised of local business leaders, reviewed 550 nominees for the award, narrowed them down to 92 finalists, and then named winners in six categories (three family business and three private business), based on a company's years in business. CTI was the winner for private companies in business 15 years or less. 

Pharmaceutical Product Development, LLC (PPD) 

(Wilmington, NC) announced the American Society for Training & Development (ASTD) has named PPD a 2013 ASTD BEST Award winner for excellence in employee learning and development. PPD was honored for implementing innovative employee training programs, which drive efficiencies in the conduct of biopharmaceutical clients' drug development programs.  

(Lexington, MA) announced Indiana University has signed an enterprise-level contract for its Clinical Trial Registration and Results (CTRR) disclosure software. Indiana University will utilize Virtify's CTRR to fulfill their regulatory obligations by disclosing their clinical trial information to the National Institute of Health's 

 (King of Prussia, PA) announced it has been ranked in the 2013 Inc. 500 list of the fastest-growing private companies in the United States. The company was ranked 192, and 21 in the software industry. 

l has named the company a winner of Best Places to Work in the Triangle. The award is part of the publication's annual Best Places to Work Awards program and recognizes Rho's achievements in creating a positive work environment. Rho was the only local CRO to be honored by the news publication. Rho also announced that 

 named it one of North Carolina's Family-Friendly 50 Companies.  

 (Wilmington, NC) announced it has been named to the annual 

 500 ranking of the most innovative business technology users in the United States for the fourth consecutive year.  

 (Raleigh, NC) announced it is the first global CRO to implement the Clinical Research Monitor Accreditation program, an internationally recognized standard for competence in clinical research monitoring offered through the International Academy of Clinical Research. 

 (Durham, NC) celebrated 25 years of dedicated service to the life science industry. Headquartered in the Research Triangle Park of North Carolina, CATO is a global, competitive contract research organization that includes an investment arm, Cato BioVentures. 

Business News

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

Business and People October 2013

The European Medicines Agency (EMA) has revealed more information about its new organizational structure. Also, conflicts of interest declarations made by senior staff have been published on the agency's website, as part of the campaign to increase transparency and openness. 

The reorganization introduces a new operating model for how medicines are managed through their entire lifecycle, and separates scientific and procedure management. Given the increasing number and complexity of applications being handled by EMA, this is intended to reinforce robustness and quality and allow development of greater specialities able to respond and support the work of the committees, according to an agency statement issued on September 16. 

A division for stakeholders and communication will aim to improve relations with stakeholders, particularly patients and healthcare professionals, as well as giving support to small and medium-sized enterprises. 

Also, new advisory groups will assist Guido Rasi, EMA's Executive Director, and other staff on operational and scientific issues in their fields of expertise. Two newly created posts, the Chief Policy Adviser and Head of Program Design Board, will strengthen the agency in this area. 

"The changes will reshape the EMA so that it is ready to handle future challenges and seize opportunities," said Rasi. "My aim is to give our scientific committees the best possible support, alongside the expertise from the national agencies, to help them keep delivering high-quality, consistent opinions. These changes will enable us to use our resources more efficiently and effectively and ensures that the agency is better prepared for future legislative and policy challenges." 

He explained that the changes reflect a renewed focus on three key elements: how to better support the scientific work of the EMA committees; how to better share the knowledge and information the agency holds throughout the EU medicines regulatory network; and how to better meet the need of the agency's stakeholders and partners. 

At the heart of the revised structure are four new divisions with responsibilities right through the lifecycle of a medicine for human use, from development to use in patients, Rasi commented. These comprise the Human Medicines Research and Development Support Division, Human Medicines Evaluation Division, Procedure Management and Business Support Division, Inspections and Human Medicines Pharmacovigilance Division. 

The revised processes are expected to be complete by next year, but the agency has pledged to ensure continuity during the transition period. Applicants, marketing authorization holders, and other stakeholders should continue to work with their current liaison staff and product team leaders unless informed otherwise, noted the EMA statement. 

In the conflicts of interest declarations for senior staff, also released by the agency on September 16, no major surprises appear to be on offer, but some interesting information is given. For instance, the Head of Information Technology, Luc Verhelst, revealed that his son, Jeroen Verhelst, is employed as a desktop specialist on the payroll of Manpower Business Solutions. Jeroen currently works on the service desk of Sanofi-Aventis Benelux in Brussels, giving support to staff. 

Also, Agnès Saint Raymond, Head of the Program Design Board at the EMA, declared that she received payments from the World Health Organization. She was paid £1,532.16 in 2011 for drafting pediatric clinical trials guidance, in addition to £1,195 for travel and accommodation to evaluate the Tanzanian Food & Drug Authority and $7,500 to cover accommodation costs during a three-month stay at the WHO. 

"My understanding is that the WHO funds come from the Bill and Melinda Gates Foundation, but I have no contact with them other than through my interaction with WHO administration," she wrote. Her appointment to the United Nations Commission on life-saving commodities for women and children does not attract any payment. 

Her colleague Emer Cooke, line manager for the International Affairs organizational entity, declared she worked for the European Federation of Pharmaceutical Industries and Associations between 1991 and 1994, and then part-time from 1996 to 1998. 

Enrica Alteri, EMA's head of the Human Medicines Evaluation division, revealed that she was employed by Merck-Serono between 1998 and 2011. Her portfolio included centrally authorized products such as Rebif, Erbitux, Gonal-f, Kuvan, Luveris, Pergoveris, Cetrotide, Cyanokit, and Ovitrelle. 

News

The European Medicines Agency has revealed more information about its new organizational structure.

EMA Unveils New Structure and Conflicts of Interest

Okay, I now know, as a former girlfriend once contended, that I am indeed part Neanderthal—but the Neanderthal 2.6% of my DNA is actually .1% less than that of other males like me—hah! I am also pleased to report that my DNA doesn't have variants associated with an increased risk for some 50 diseases, although I do have a marginal increase for five others, none of which, fortunately, seem quite that bad. I have a slightly increased sensitivity to Warfarin, and am a slow metabolizer of caffeine, which keeps me awake some nights. Despite the evidence on my hairbrush, I am unlikely to lose my hair anytime soon, am more of a sprinter than a distance runner, and am not bothered by bitter-tasting foods. And I definitely do not have a tendency toward alcohol flush—no matter what my wife insists. I know all this because my 23andMe genetic profile tells me so.  

For those who haven't checked it out yet, 23andMe offers genetic insights for the common man over the web. While 23andMe hasn't fully sequenced my DNA, it's amazing how much it can tell me about my genetic profile from the half-teaspoon of saliva that I sent along with my $100 payment. The reports on my health risks, drug response, inherited conditions, traits, and ancestry are pretty comprehensive and often engrossing, but a lot of the results also depend on the answers I provided in a series of questionnaires I filled out to help them flesh out my genetic profile. 23andMe is also quite a sensitive and empathic confidante; it will repeatedly confirm if I really, really want to know certain results—such as a higher than normal susceptibility to some serious diseases—before it breaks the possibly bad news. 

Some of this information, when shared with my physician, might directly help open the door into the realm of personalized medicine. You remember personalized medicine, which was supposed to become a rallying point for teeming, venture-funded bioinformatics start-ups that emerged just when the Human Genome Project was announcing completion of its draft human genome at the beginning of this century. 

Now, more than a dozen years later, we're still waiting for the breakthroughs. Most of those promising new bioinformatics companies from 2000 are no longer with us, while the rest of us are still prescribed drugs by traditional methods, often a matter of experience-based trial and error. There have been notable inroads particularly in oncology, such as the HercepTest that identifies over-expression of the HER2 protein and identifies which breast cancer patients will most benefit from Trastuzumab. But in most cases medicine has not yet gotten nearly as personal as we patients might like. 

Meanwhile, drug research is still burdened with tales of once promising new drugs that fell by the wayside during clinical trials even when they showed a profound effect in one subset of patients but had no discernible effect or, worse, exhibited serious safety concerns in too many others. In my case, my 23andMe profile predicts substantially increased odds for me of experiencing myopathy on statin therapy, which might have been useful information for my physician when he prescribed a statin to treat my elevated LDL cholesterol a few years ago—which I ultimately abandoned along with the French fries after a month's worth of annoying muscle aches.  

If only we could explain why certain drugs work so well for some patients and not others, and create simple, predictive diagnostic tests (also known as theranostics) that can identify the positive responders while screening out those most vulnerable to its adverse events—perhaps we could reclaim from the scrap heap of discarded drugs a few that showed extreme promise for some while simultaneously introducing too much hazard for too many others. If so, maybe we'd learn that the next set of wonder drugs already exist—if we only knew how to prescribe and use them properly.  

Given that 23andMe is already giving me so much insight into my risk factors and likely response to certain drugs for my $100 and spit investment, why haven't we progressed further on the personalized medicine frontier by now? 

Well, to reinvigorate such failed drugs we need data—lots of data. We need to pool diverse sources and types of data together in a consistent manner so we can probe the data systematically to help identify more of those theranostic biomarkers that may inform physicians as to which type of drug is most likely to have the best benefit/risk ratio. We need to build much more understanding of the genetic profiles of patients and seek out genetic markers that may predict their response to various types of drugs to inform the physician's treatment plan with predictive evidence.  

As I've noted in prior columns, the data transparency movement may help make clinical study data more widely available, but the utility of such data is often hampered by insufficient data standardization while availability is obstructed by critical concerns such as data privacy. Including personal genetic info among such data is seen as even more threatening—is this something my insurer could use against me? And yet it seems that many of us customers willingly grant 23andMe consent to allow our very private data to be used for multiple research purposes. So maybe it's less of a barrier than commonly perceived—as long as we get in the habit of systematically securing the proper kind of informed consent for research that enables reuse of the data for expanded research purposes—and have adequate assurances that the data won't be misused or confidentiality breached. 

But then science always marches on, and research is ongoing in many areas. But what does it take to finally achieve what Malcolm Gladwell calls the 

, when a formerly emerging trend, idea or behavior finally turns the corner and develops enough sudden momentum to spread like wildfire? Think of a roller coaster slowly crawling over the summit of its first hill before accelerating into the next exhilarating moments of sheer terror. One of the criteria for a successful tip is stickiness, and what is stickier than finding ways to treat illness effectively for affected patients with minimal side effects? It's all in the magic of conjuring the right potion—if we only knew how. 

But maybe the tide is finally turning. As I've noted previously, there's much more activity around the world on translational medicine looking at combining such diverse data to fuel new research activities. And there are prominent examples such as the innovative I-SPY2 trial, a large-scale adaptive trial that is exploring multiple interventions for breast cancer patients and collecting a broad range of clinical trials data including genomics, proteomics, pathology, and imaging data to help identify biomarkers associated with the most beneficial treatment combinations.  

And we're finally seeing more traction in the use of data standards, with expanded interest among European and Japanese regulators, who traditionally did not require submission of data to accompany product-licensing applications. We're now seeing a more consistent effort at FDA to capitalize on CDISC standards, partly as a result of the FDASIA and PDUFA V mandates for therapeutic area data standards, and rapidly increasing adoption by sponsors as a result. And the involvement of Trans-Celerate Biopharma, a consortium of top sponsors, in the CFAST therapeutic area data standards initiative is a game changer—since it elevates awareness and commitment to data standards at the highest executive levels of the pharmaceutical industry.  

While some will say that CDISC standards are not adequate to fully realize the vision, it's also pretty clear that they are the only proven set of global standards particularly designed to facilitate clinical research, and also the set most ready for prime time. They clearly are better than any other option, and they pass the stickiness test. They've also been designed explicitly to be complementary and compatible with healthcare standards—while still representing research in a way that's familiar to the current research community and compatible with most existing tools. Of course we may find better methods in the future through the semantic web and other emerging technologies—but such natural growth and evolution is only to be expected. What's important is to build now on what is best known, most used, and most feasible at this time—we can only go up from there. 

, Gladwell tries to explain some of the factors that have made some people brilliant successes, while others never achieve their full potential. One of these is serendipity—the fact that a group of people working in a specific area somehow came together—or even competed—with the right tools, connections, and circumstances to succeed at a special point in time. Maybe it's finally time for the outliers of science to work together to really begin to realize the extraordinary promise and vision of personalized medicine. It took over a decade for EDC to hit its tipping point, more than seven years for CDISC SDTM to get full traction. Maybe next time we'll do it in five. But let's tip the balance now while we can. 

Meanwhile, I wonder if there's a genetic basis for the headache I get from drinking certain wines. I can't wait for 23andMe to find out. 

is Chief Technology Officer for the Clinical Data Interchange Standards Consortium (CDISC). He resides near Chicago, IL, and can be reached at 

CTI Insights

Is it time to realize the extraordinary promise and vision of personalized medicine?

Personalized Medicine, Data, and Me

Despite the growing need for pediatric-approved medications, clinical trial enrollment for pediatrics remains challenging. Unlike adult clinical trials, the decision to enroll in a pediatric trial introduces a new series of logistical and emotional complexities for parents, physicians, and the child. 

In a white paper completed by Blue Chip Patient Recruitment, "Accelerating Recruitment for Pediatric Clinical Trials: Connecting Parents, Children, and Investigators" (

), primary market research explores the motivations and barriers a parent faces when considering clinical trial opportunities for their child, as well as the challenges physicians experience when recruiting children for clinical trials.  

Understanding the true motivations and worries behind a parent's decision to enroll their child in a clinical trial is essential for successful enrollment. Since many medications have never been studied in children, sponsors and investigators need this type of research to successfully address the changing pediatric healthcare environment. 

In looking at which parents were most interested in enrolling their child in a clinical trial, they tend to be younger (25-44), well-educated (college/post-graduate degree), and employed full-time. The incorporation of such demographic insights into parent-facing communication is fundamental to more effective patient enrollment strategies. Physicians need to tailor their communications to this highly-engaged, educated, and active parent.  

Many parents state the efficacy and their satisfaction level of their child's current medication as a major motivator in potential clinical trial opportunities. Nearly 85% of the parents who were "very or somewhat satisfied" with their child's current medication indicated they would be willing to switch their child to a new medication option. One parent stated, "It [the medication] could always be better." This means that even though parents may be very or somewhat satisfied with their child's current medication, they're always looking for something better that could help their child more.  

When educating parents on clinical trial opportunities, communications are led by physicians and tend to consequently focus on topics they believe are most critical. Specifically, nearly three-fourths (74%) of physicians point to altruistic benefits as a key motivator in conducting these studies. However, when we asked parents the same question the story changed. Only 49% of parents listed altruism as a top motivator. Instead, parents are concerned about how a trial will affect their child specifically; 57% of parents wanted to be assured that their child's health will be closely monitored—a concern that physicians did not even list among their top four motivations. Physicians affiliated with academic institutions cited different impressions of parental motivations than physicians conducting a study through a private practice. Four out of five (82%) private practice physicians believed a major motivation for parents is the access to free medical care. Academic investigators cited altruistic motivations as a likely incentive for involvement (60%), whereas private practice physicians suspected this was not the case (9%). 

To overcome this inconsistency between physicians—and thus address parents from a more effective, consistent platform—sponsors should consider developing two sets of communications. These separate approaches may allow physicians to communicate to parents in ways that address the concerns and motivations of physician and participant, while still establishing consistency. 

In the study, every study physician preferred face-to-face communication (100%) and while the parents agreed that face-to-face communication was a preferred method of communication, they were also open to other forms of communication. Written communications were favored by parents, specifically e-mail (55%) and physical letters (32%) whereas only 6% of study physicians favored e-mail and 0% letters, respectively. 

Accommodating the communication preferences of parents may facilitate the removal of structural communication barriers to potential enrollment.  

To adequately address the growing prevalence of R&D needs for pediatric patients, coordinators of pediatric clinical trials must seriously reconsider approaches to organizing studies. Given the wide range of complexities involved in coordinating pediatric clinical studies, it is essential that insights into the perceptions of parents and physicians be acquired and considered in study designs, so as to more effectively enroll pediatric patients. 

—Neil Weisman, EVP/General Manager, Blue Chip Patient Recruitment

Despite the growing need for pediatric-approved medications, clinical trial enrollment for pediatrics remains challenging.

Bridging the Disconnect in Pediatric Clinical Trial Recruitment

	The use of CROs by pharmaceutical sponsors across all therapeutic areas and phases increased 44% between 2007 and 2011, according to the Association for Clinical Research Organizations. Lazard Capital Markets, Life Sciences, noted in 2010 that the largest pharma sponsors outsource nearly 100% of laboratory services (central and bioanalytical), as well as Phase IIIb and Phase IV studies, to CROs and service providers.

	With this increased use of outsourced relationships, as well as a growing segment of pharma utilizing strategic relationships with outsourced providers, the need to integrate data, systems, processes, and communications with their CROs is a vital concern. How does the industry balance these needs, as well as achieve their objectives within an outsourced relationship structure?

took four market research reports that were released in 2013 to assess and evaluate the current state of sponsor and CRO relationships. Those reports are:

		"Strategic Partnerships 2013, Transforming and Unlocking Value in Biopharmaceutical Development," based on third-party research released by Parexel (April 2013).

		ISR Reports, "2013 Phase II/III CRO Quality Benchmarking Report," (April 2013).

		Vantage Partners, "Sponsor-CRO Collaboration Study," (May 2013).

		The Avoca Group, "Quality Consortium, Summit 2013, Optimizing Approaches and Establishing Best Practices in Quality Management of Outsourced Clinical Research, Executive Summary Report," (June 2013).

	Reportedly, more and more pharmaceutical sponsors are moving toward more strategic relationships...they contract with less numbers CROs and service providers at any one time; they form closer ties and business integrations to theoretically build efficiencies and save money; and use more shared approaches to expertise, input, and control. However, on the way to this road, there have been barriers and challenges that companies have needed to overcome.

	The Vantage Report lists barriers to all outsourced relationships, and the one most cited by CROs is that they are not involved early or deeply enough in the initial trial and protocol design and planning stage.

	This has been a consistent statement over the years from CROs, that CROs aren't used for their true expertise and are basically the "arms and legs" of the sponsor, when they also want to be the brains. But what do sponsors really want? In the ISR report, currently given their druthers, sponsors want flawless execution. The report asks between flawless execution or drug development design expertise and experience, what do you want from a service provider: 64% go for execution and 36% expertise. When asked what they see three years from now based on their unique development needs, the sponsors' execution needs go down slightly to 59% versus 41% for expertise.

	In the Vantage report, the analysts give credit where CRO credit is due in the area of protocol design and study planning and note the following key considerations in planning a clinical trial for which CROs could offer useful insight and information:

		Where are the sites with the highest recruitment potential?

		Which investigators have the best track record, in terms of both recruitment and protocol execution?

		What challenges have other companies run into when executing studies of this type and/or in these regions?

		What are the adverse events that could derail the timeline? How likely are they?

		What has been done in other trials to mitigate or eliminate risks?

	Risk mitigation or risk management in clinical trials is determined and calculated in various ways in project management. For example, most sponsors already have a running list of the Key Risk Indicators (KRIs) in a trial either from a clinical basis or a project management basis...those things that are monitored consistently for a problem. KRIs, and the ability to detect and manage them can be a benchmark or metric by which to assess the performance of a service partner, if they are standardized to compare apples to apples. Some groups, including the Avoca Group, use a standardized list of the KRIs by which agreement and performance between the CRO and sponsor can be the basis.

	At the Avoca Quality Summit, Ann Meeker-O'Connell, Acting Division Director for Good Clinical Practice Compliance in the Office of Scientific Investigations, CDER, FDA, spoke via teleconference and noted that it is critical to determine the right partner for each industry activity. And interestingly, effective oversight is a two-way street with communication as its transportation. If sponsors or CROs do not outline activities or identify where risks are, and initiative is not taken, activities can fall through the cracks.

	"All standards emphasize communication as an essential part of risk management," Meeker-O'Connell stated. However, there should not be an exhaustive list of issues, rather, it should be about planning efficiently, such as the opportunity to focus resources and keep track of things that aren't being addressed.

Is it difficult for CROs and sponsors to agree on risk? 

The Avoca Group asked sponsors: In general how difficult is it to gain agreement between your company and your clinical service provider partners about the probability and importance of various risks associated with clinical trial conduct? Only 4% said very difficult, 21% said easy. The remainder was weighted toward slightly difficult and somewhat difficult.

	When asking CROs the same questions, 6% said very difficult, and 16% said easy. Again the remainder was in the area of slightly to somewhat difficult, not by large margins of difference.

	The Parexel survey noted that the outsourcing relationship today has barriers and the top was limited alignment of goals and objectives (which could be construed as risk) and the last barrier a lack of information sharing. However, it noted that "as strategic partnerships evolve, the model will provide biopharmaceutical companies and CROs with a strong foundation to address these concerns. The hallmark of well-executed strategic partnerships is how efficiently these dynamics are managed through the partnership infrastructure."

	The Strategic Partnerships 2013 was a first stab at assessing the state of strategic partnerships, a business model that only came into being within the past five years. So what attributes among CROs are needed for that strategic partnership? Listed in order of importance:

	The ISR Benchmarking Report asked the most important service provider attributes-overall, not just strategic-with the following chosen as most important: overall value, prior positive experience with that provider, project manager quality, therapeutic expertise and contingency planning, and risk management.

	When given a full choice of attributes that are gaining importance in the past 12 months, the report noted low cost jumps to number two, and global footprint to number five. However, any attribute related to metrics such as metrics for site start-up, for sites or recruitment, database lock timelines, or turnover metrics, the numbers were quite low. The analysts for this report said: "One thing that strikes us about the selection data is how far down on the list the 'metrics' based attributes are. As important as these attributes are to the success of a project...we would expect a CRO's ability to demonstrate a successful track record in these to be more important in the selection process."

	Interestingly, the discussion of metrics is fluid in the chosen reports. As noted above, ISR analysts were surprised that metrics weren't rated higher. The Vantage report includes a discussion that one metric, first person in, became so over-concerning on both parties, that other focuses fell by the wayside. So Vantage recommends: Measure what matters-avoid the temptation to measure too many things, or focusing on what is easy to measure. Think carefully about which measures ought to be captured at which levels of the relationship. Consider starting by looking at the data currently captured by both sponsor (for in-house trials) and CRO (for its own purposes and for other sponsors). Most of the important data will be on such a list, and it is just a matter of filtering through it.

	Truly there is more to talk about in CRO and sponsor relationships than can fit in any one article. These reports range from 18 to 245 pages, some are free and others available for purchase. Beyond the pages of our magazine and website, many venues discuss the state of these relationships in the clinical trials industry including CBI's CRO and Sponsor Business Process Integration, and the annual IIR Partnerships conference. However, most will agree that the foundation of any relationship is trust, and getting to a point where companies can trust each other to look out for their best interests is hallmark of outsourcing.

is Editor-in-Chief of Applied Clinical Trials, e-mail: 

	1. "Strategic Partnerships 2013, Transforming and Unlocking Value in Biopharmaceutical Development," based on third-party research released by Parexel, (April 2013), 

http://www.parexel.com/etc/strategic-partnerships-report-2013/

	2. ISR Reports, "2013 Phase II/III CRO Quality Benchmarking Report," (April 2013), 

Companies trusting each other and looking out for each other's interests is the hallmark of outsourcing.

Applied Clinical Trials-10-01-2013

ACT Cover

Relationships Between Advocacy Groups and Pharma

Does European Policy Still Have Room for Clinical Trials?

Leveraging Pharmacists as a Channel to Raise Clinical Research Literacy Among Patient Communities

Business and People October 2013

EMA Unveils New Structure and Conflicts of Interest

Personalized Medicine, Data, and Me

Bridging the Disconnect in Pediatric Clinical Trial Recruitment

The State of CRO and Sponsor Relationships

Smart Patients, Smarter Trials

Sunshine Reporting Raises Concerns for Sponsors, Investigators

Assessing Drug Impaired (or Enhanced) Driving

Applied Clinical Trials Digital Edition - October 2013