What next for clinical research?

ACRO’s member companies believe that strengthening public confidence in the research enterprise is important, and we have taken several steps in support of that goal. First, In terms of strengthening public confidence in the research enterprise, ACRO developed a Code of Ethics for CROs, which is endorsed by all of our member companies. In looking to further public understanding of clinical research and its importance, we work closely with our colleagues in other Associations, such as the Pharmaceutical Research and Manufacturers Association (PhRMA), and were pleased to endorse that group’s ‘Principles on the conduct of clinical trials and communication of clinical trial results’.

As a key stakeholder in the development of new biomedical products globally, ACRO recognises that the recruitment and retention of clinical trial volunteers is vital to the process of bringing new drugs and new treatments to the patients that need them. A public that is well-educated about the research enterprise and confident in the activities of all the players – from sponsors and investigators to CROs and regulators – will, we believe, strongly support clinical research, and ACRO intends to continue its efforts to foster the public’s understanding of the crucial importance of clinical trial research.

Clinical trials

Clinical trials are the bridge between the laboratory and the doctor’s office, and without clinical trials there would be no new medicines, no new treatments. The paradigm is straightforward and rigorous, allowing the evaluation and approval of new drugs within a calculus of risk and benefit.

Allowing the study of treatments across groups of patients in a controlled and methodical way, the clinical trial has led to spectacular advances in lifespan and quality of life, and to the concept of evidence-based medicine. But, as the US Food and Drug Administration (FDA) pointed out in its 2004 white paper, Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products, the current development pathway is becoming increasingly inefficient and costly; the testing and approval of new drugs and new products is taking longer and longer and costing more and more.

The FDA and the EMEA both are committed to looking at new research paradigms, such as the use of biomarkers and adaptive trial designs, and perhaps even a ‘continuous’ model of drug development, with smaller and targeted trials, faster approvals, and ongoing safety evaluation of real-world practice over the lifetime of a drug.

With our extensive experience with the conduct, monitoring, analysis and submission of clinical trials, CROs will be a key participant in the development of these new models of drug testing and development.

The influence of ACRO

ACRO is a voluntary association whose member companies are dedicated to advancing the quality, efficiency, and safety of biomedical research. We are committed to spotlighting the strategic value of clinical outsourcing and to elevating the global CRO industry as a valued partner in drug development. We work collaboratively with clients, regulators, legislators, patient groups, and other industry organisations to increase the understanding of, and promote the value of, clinical research and biomedical product development.

We believe that the protection of research participants and the safeguarding of data integrity are core functions of the CRO, and we work to provide a credible and unified voice on clinical research issues for all CROs. Leading by example, our member companies spearheaded a project to develop ‘standardised’ clinical trial data collection mechanisms (which has since been taken over by the Clinical Data Interchange Standards Consortium or CDISC), and we regularly meet with clients to discuss best practices in outsourcing. Steady interaction with regulators – for example, in representing the CRO industry in quarterly meetings of the EMEA’s EudraCT-TIG working group – aims to improve the efficient conduct and oversight of clinical trials, and to foster greater collaboration across stakeholders.

Critics of clinical research

By its nature, medical research with human beings involves a measure of risk. However, clinical research is essential to the development of new drugs and new treatments, and all participants in the research enterprise are committed to protecting the rights and safety of research participants. Only regulatory authorities such as the MHRA and the FDA, who assess whether the research program is properly designed and scientifically valid, can approve clinical trials. Every clinical trial is also reviewed and approved by a local ethics committee or IRB, whose purpose is to safeguard the rights and welfare of research volunteers.

Clinical trials are run by qualified investigators in hospitals and academic institutions, and often are coordinated and overseen by specialised research organisations and CROs, such as the members of ACRO. For CROs the protection of human research participants is a core function, and ACRO members subscribe to a code of ethics that places the rights and safety of research participants first.

Failing faster through new technology

As I mentioned, the standard The current product development model of research has become too expensive, too time-consuming and inefficient in producing the new drugs and new treatments that are needed by patients. In its 2004 Critical Path white paper, the FDA suggested that predicting the ultimate success of a potential new product in development is almost impossible today; noting that four out of five products that start clinical development fail to make it to market, and that a full 50 percent of drugs that undergo phase III trials turn out to be unsafe or not effective enough or cannot be produced efficiently.

In fact, the FDA said, the outlook is worsening: a drug entering phase I testing in 2000 actually had a lower chance of winning approval than one that began testing in 1985.

Clearly, these numbers are disturbing, and suggest that we cannot continue to rely upon what the FDA called the “hit or miss” evaluation tools and the processes and procedures of the last century to develop this century’s breakthrough medical advances. We – sponsors, investigators, CROs, regulators – need to identify and prioritise the bottlenecks along the development pathway, and consider mechanisms, from the development of meaningful and reliable biomarkers to the use of adaptive trial designs, that hold the promise of significant improvement.

Certainly, research designs that will allow us to ‘fail’ less promising drug candidates faster constitute an important approach. In our regular meetings with the FDA, ACRO and its members have discussed a variety of potential initiatives along the Critical Path, and I would mention, again, that we spearheaded an effort to develop ‘standardised’ clinical trial data collection mechanisms, a project which has now been taken over by CDISC.

The future of clinical research

In recent years, an increasing proportion of resources involved in clinical trials has shifted from the pharmaceutical industry to CROs. According to the Tufts Centre for the Study of Drug Development (CSDD) – which conducted the first independent, third-party examination of the CRO industry’s rapid growth – this realignment has increased the speed and efficiency of the pharmaceutical product pipeline, while maintaining high levels of data quality and regulatory compliance.

Among other things, the Tufts study found that trials with significant CRO involvement are more likely to stay on schedule than those with less CRO involvement. Typically, data from such studies were sent to regulators more than 30 days closer to the projected submission date than studies with less CRO participation.

CROs – with their global networks of laboratories, clinicians, statisticians and other professionals – provide research experience that can be harnessed quickly and cost-effectively, without sacrificing safety or data quality. Leading CROs are experts in the conduct of clinical research and this expertise explains, in part, the strong industry trend toward outsourcing as an effective strategy to meet the challenges of today’s drug development environment.

Future plans for ACRO

Representing a global industry, ACRO makes contact with regulators, policy makers and colleague associations worldwide. In Europe, for instance, we have had discussions with the European Commission and the EMEA regarding issues in the implementation of the Clinical Trials Directive. In recent months, a delegation of our members took part in a two-day meeting with EU data protection authorities, which was organised by our colleagues in the International Pharmaceutical Privacy Consortium (IPPC), and I had the pleasure of presenting a talk on the impact of outsourcing on drug development to the 5th Annual Partnerships in Clinical Trials Congress in Brussels. We are also exploring opportunities for collaboration with EUCROF, a federation of European CRO associations, and are similarly hoping to establish relations with relevant committees and working groups of the EFPIA in the future. Finally, we are very much cognisant of regulatory issues in the emerging research markets of India and China and have made preliminary efforts to present ACRO as the voice of the CRO industry in consultations with policy makers in those countries.

Dr Douglas Peddicord is the Executive Director of the Association of Clinical Research Organisations (ACRO), representing leading clinical research organisations that provide a wide range of research and development support services to pharmaceutical, biotechnology and medical device companies globally. ACRO works to provide a heightened awareness of the critical role that CROs play in the development of new drugs, new devices and treatments.

Dr Douglas Peddicord: “The standard current model of research has become too expensive and too time-consuming”