Clinical Trials

Vito Mangiardi, President of North American Operations at AAIPharma, and David Spaight, President of MDS Pharma, talk clinical trials, ethical standards, CROs and where the industry is heading.

NGP. The number of people willing to participate in clinical trials is dropping. Is outsourcing a solution to this problem?
DS. As a global CRO responsible for conducting more than 800 Phase II – IV trials involving more than 17,000 investigative sites and the recruitment of nearly 200,000 patients in the last five years, we have to disagree with the statement. The willingness of patients to participate in clinical trials is driven by a number of factors such as, but not limited to, disease type, stage of the disease, the current availability of effective treatment, inclusion / exclusion criteria of the clinical trial, and patient awareness and understanding of clinical trials. In recent years, clinical trials have included patients from Eastern Europe, Asia Pacific and Latin America, delivering access to larger patient populations. CROs can often offer cost and time effective solutions to overcome recruitment challenges, given their global reach and expertise in volunteer and patient recruitment strategies and project management.

VM. In my experience, the real issue is patient recruitment. For example, if you need 600 patients total for an infectious disease product, you could recruit, say, 150 of them in North America and Europe very rapidly. However, if you expanded your recruitment to South America, Asia, and Eastern Europe, you can meet your client’s timelines quite aggressively. So, our experience is exactly what you are indicating – outsourcing is a solution - there is more outsourcing from the pharmaceutical and the biotechnology companies into companies like ours. There is significant outsourcing that is going on in a variety of different therapeutic areas. We feel that the ability to accommodate these particular pharmaceutical companies and biotech companies is critical. The way to accomplish this is to have to have a lot of specific associations with investigators, and we are doing this. We feel there is not a lack of patients if you look at it from a global perspective. We are able to fill our clients’ needs because we are not located in any one location. We are located in a lot of different locations and we’ve connected to investigators that really allow us to get to the specific patient populations.

NGP. It has been suggested that many developing countries do not have the same ethical standards for the treatment of human subjects as we do in the US. How do we ensure informed consent in such regions?
VM. AAI Pharma takes a lot of pride in having dealt with this effectively. We conduct our clinical trials operations in compliance with strict standard operating procedures consistent with both European and US regulations and guidelines, and also internationally accepted guidelines in the International Conference of Harmonization (ICH). They include compliance with professional good clinical practices and GCP requirements which require patient informed consent. Regardless of where the study is conducted AAI Pharma assists our drug development clients in the drafting of proper informed consent, all required elements, including a complete explanation of the purpose of the research. We deal with trials across several regions and although some of the countries, as you’ve indicated might have a different quality of life and different standards, our own standards are in full compliance and are harmonized through all these countries to protect clinical trial participants.

DS. At MDS Pharma Services, our global processes and procedures support full compliance with GCP, ICH and regulatory requirements of the countries where the clinical trial will take place. Our informed consent documents are translated into the language of the volunteer or patient, and the documents are verbally explained by qualified personnel. Adequate time is provided to allow participants to review and consider the information prior to their participation.

NGP. How will global trial management capabilities continue to evolve in the coming years and what effect will they (the capabilities) have on the CRO industry?
DS. In Phase II-IV, we foresee continued geographical expansion, particularly in Asia Pacific and Latin America, and innovative solutions for data flow through further investments in IT for electronic data capture and electronic document management.

Focusing on the evolution of management capabilities, we envision the increasing worldwide use of sophisticated computerized clinical trial/clinical program tracking systems – particularly the spread of such capabilities into regions where they have been less available. This will be particularly important in improving the management of scope-of-work changes needed to accommodate regional situations as they arise. The CRO industry will have to become much more nimble in this regard, and willing to adopt new technologies that will offer time and cost savings while delivering high quality data.

VM. There will be significant changes as we move forward. In the long term the focus of the CRO’s in this particular arena is logistics. A key component of what we do is logistics, but I think what we are really looking at is bringing an added-value component to this. An example of this is AAIOncology group, one of our therapeutic specialty groups. This group provides significant medical and technical depth to our clients who are developing cancer products globally. This medical depth is something AAI Pharma believes should extend to a number of therapeutic areas. I also believe that the industry is now focused on productivity – where there hasn’t been rapid achievement in the past. Productivity hasn’t changed significantly for a while. The major change that will affect the CRO industry—and drug development productivity-- is in real-time data. In many of the trials being conducted today data often comes out too late. Essentially this can result in retroactive data resolution issues rather than resolving data issues in real time. Real-time data allows us as an industry to be proactive. I believe very strongly that the CRO industry is going to require greater productivity, and part of that greater productivity is going to be achieved with real-time data.

NGP. By re-evaluating study planning, use of technology and recruitment, disconnects in project management can be uncovered and innovative approaches identified. How, in your opinion, will drug development sponsors embrace a new approach?
VM. Technology is extremely important in moving forward into evolved EDT type systems and clinical trial management systems, global project management and monitoring is going to change as a result. In addition, you must have excellent project management, and project managers and program managers that span the globe. They have to understand the cultures, manage across various countries, and understand and be very connected and sensitive to the sponsors’ needs. They must also be able to provide the sponsors a real-time perspective. From a global perspective, I believe that drug development sponsors will embrace this new approach. Why? Simply put, because it is going to increase their productivity and efficiency in clinical trial delivery.

DS. Clients should embrace innovations such as information sharing over the web with proprietary access, provided these innovations improve process efficiency, effectiveness and accuracy while maintaining high quality results. The advancement and widespread availability of Internet access has contributed to increased awareness of clinical trials among investigative sites, patients and the general public, making the Internet a valuable component in recruitment strategies. Drug development sponsors and CROs have embraced this technology in recent years to assist with patient, investigator and healthy volunteer recruitment.

NGP. People are looking beyond genomics and proteomics into higher-content information. HCS (high-content screening) in cell-based assays is a strong trend for the future. Others see a growing trend in gene expression analysis from the perspective of RNA-focused research. Where do you think the future is taking us?
DS. The rapid progression of genomic and proteomic science have enabled pharmaceutical and biotech companies to understand the interactions between drugs and their biological targets in greater depth than before. There is no doubt that personalized medicine will be an important element in future drug development considerations, but, there are a number of questions that need to be carefully assessed at this point in time: e.g. Can the market afford ever-increasing prices for pharmacogenetically-developed drugs? And is it economically viable for the pharmaceutical and biotech industries to develop high-cost but highly targeted therapies for small patient populations? However, the industry is making progress through the widespread use of biomarkers and translational medicine in many drug development programs. Biomarkers can streamline clinical development by providing earlier objective and evidence-based information through accurate and precise pharmacodynamic measurements, thereby facilitating efficient and effective development of drug candidates. To meet the industry’s needs in biomarker science, MDS Pharma Services has a Development and Regulatory Services team with wide-ranging scientific, clinical, and regulatory expertise in this area to guide clients in their drug development programs.

VM. All these areas are extremely important. The issue has been that there hasn’t been connectivity and real application in terms of clinical trials. In the future, I think this will move into personalized medicine. You will see that it is already happening in various areas. We are engaged in trials not only with real-time data but with trials that are now focused on a personalized approach to clinical trials. In the past there have been a lot of blockbuster drugs, and when you look at the marketplace the real efficacy of most of these drugs is about 50 percent. I think the focus of the future will be on developing drugs that are effective in these sub-populations so that the efficacy is going to 90 or 95 percent. It will be more personalized in these specific areas of disease than it has been in the past. This will be a significant improvement, and you are going to see much greater efficacy in these particular drugs as we move ahead to the future.

NGP. What ensures a pharmaceutical company that their CRO partner has the global outreach and experience in a therapeutic area?
VM. The best way for a pharmaceutical company to be assured of global outreach and therapeutic depth is to have opened specific discussions with a CRO’s project management leadership. There are some key ingredients that are essential, such as excellent program and project management leadership in therapeutic areas, in-depth technical knowledge and expertise, experience in the various areas of a therapeutic area, well trained staff all the way from monitoring to bio-statistical staff and medical to data management staff, and of course a harmonized approach regardless of location. At the core of all this is standardized training to ensure you are able to continue that technical depth and technical understanding. At AAI Pharma, we have all the key ingredients, to make an impact and bring real productivity, real efficiency, and added value to the marketplace and to our clients.

DS. In many respects, CROs are selling the collective experience and knowledge of their people. MDS Pharma Services gained important experience in managing a large, high-profile Phase III clinical trial of an anti-malarial drug. The trial involves thousands (2,550) of malaria patients in China, Laos, Thailand, Burkina Faso, Kenya, Mozambique, Uganda, Zambia and India, where patient recruitment started in November 2006. And in our therapeutic specialty areas of oncology and metabolic disorders, the proof is in our people and our access to patients through strong investigator networks.

MDS Pharma Services President David Spaight has more than two decades of experience in the global life sciences industry and a track record of successfully building strong businesses.

He has a Bachelor of Science in Chemistry and a Masters in Business Administration, both from the University of Michigan. In 2007, he was named Chair-Elect of the Association of Clinical Research Organizations (ACRO -- www.acrohealth.org), which represents the clinical outsourcing industry to regulators, biopharmaceutical clients, policy makers and the public in the United States and around the world.

Vito Mangiardi, AAI Pharma President of North American Operations, has nearly 25 years of international experience within the pharmaceutical, biotechnology, health services and diagnostic industries.

Prior to joining the Company, he served as Senior Vice President and Chief Operating Officer for the Late Phase Unit for Quintiles Transnational Corp., responsible for the management of all aspects of pharmaceutical development. Prior to this, Mr. Mangiardi served Quintiles as Senior Vice President of International Clinical Development Services. Mr. Mangiardi’s previous leadership positions include President and Chief Executive Officer of Clingenix, Inc. and President and Chief Executive Operating Officer of Diagnostic Laboratories, Inc.