In a first-of-its-kind book, “Re-Engineering Clinical Trials,” co-authored and edited by Brendan Buckley, ICON’s chief medical officer, and Peter Schüler, ICON’s senior vice president of Global Medical and Safety Services, details specific, holistic reforms for trial design, clinical operations, and portfolios.
 
Joined by co-authors at AstraZeneca, Bayer, Boehringer Ingelheim, the Tufts Center for the Study of Drug Design, and other institutes and companies, the book compiles a comprehensive collection of reforms for a progressive model of drug development aimed at driving faster change in research environments increasingly restrained by companies, not regulators.
 
The book addresses some critical questions about the fundamentals of clinical development, such as why good drugs fail, why so many expenditures in trials don’t benefit patients, and how other industries may have already invented what’s needed for beneficial reform.
 
The suggested reforms do not require new technologies or methodologies, but innovations that are either available in other industries or have already received regulatory approval and are currently used in clinical trials.
 
Along with Brendan Buckley and Peter Schüler of ICON, Ken Getz, Director of Sponsored Research Programs & Research Associate Professor at Tufts, share their assessment of critical reforms, current pitfalls associated with clinical trials, areas in most need of an overhaul, and industry hurdles. – Kristin Brooks
 
Contract Pharma: Currently, what are the major pitfalls associated with clinical trials and how might they be overcome?
 
Ken Getz, Tufts CSDD: There are a number of major pitfalls, the heart of which is protocol design complexity and its adverse impact on clinical trial efficiency and cost. At the present time, clinical trial designs have a large number of tertiary and exploratory endpoints, very strict eligibility criteria, and numerous operating challenges including large numbers of investigative sites spread out across 30 to 40 countries. In addition, a vast amount of data is collected for each clinical trial that must be cleaned, curated, managed, and archived. These conditions have contributed to delays and inefficiencies, rising costs, poor and declining patient recruitment and retention rates, and higher failure rates.
 
The upcoming Re-Engineering Clinical Trials Summit, hosted by Tufts CSDD and ICON, will touch on these pitfalls and then focus on new strategies, practices, and policies — such as feasibility review mechanisms, risk-based monitoring, adaptive trial designs, new data analytics, and patient centered and inspired solutions — designed to simplify protocol design, improve clinical trial feasibility, and reduce cost and inefficiency.
 
Contract Pharma: In what specific areas do clinical trials need an overhaul? What aspects remain antiquated?
 
Brendan Buckley, ICON: The most striking issue with clinical trials at present is the slow progress of data flow, once gathered at a trial visit, into the database. It can frequently take weeks. In an era of instant information enabled by mobile devices and broadband connectivity, this should be unacceptable but is, strangely, the norm. 
 
Contract Pharma: Are there specific regulatory hurdles or current obstacles associated with reforming clinical trials, if so, in what areas?
 
Brendan Buckley: Regulators have frequently attempted to lead the industry in modernizing and rationalizing processes in trials, for example in their advocacy of risk-based monitoring and of adaptive trial design. The deeply conservative approach of industry has mostly been slow to embrace such reforms and there has been little evidence of a concerted attempt to manage change, despite this being enabled by mature processes and by technology operating in other spheres.
 
Contract Pharma: How important are e-clinical solutions in achieving reform?
 
Peter Schüler, ICON: In our 21st century, we create an increasing volume of data in digital format: photos, e-mails, books, and music. Clinical trials are not exempt from the digital trend, particularly when it comes to patient engagement. The new generation of patients will only accept trials that allow them to use their smartphones, tablets, and interactive watches as part of the study. In general, industry is embracing e-clinical solutions, from accepting digital signatures on informed consent forms to capturing endpoints with smart devices. As a welcome “side effect,” these technologies allow for easier data transmission, storage, and analysis. Despite the obvious benefits, agents of change will need to continuously reinforce the advantages of digital clinical trials to decision makers.
 
How important is the establishment of global standards in achieving reform?   What progress is being made and where are greater efficiencies needed?
 
Ken Getz: It’s very important to establish standard practices and credentials across numerous clinical research domains including: professional and organizational certification and accreditation, technology solution compatibility and interoperability, operating procedures, and quality and performance metrics. They assist in building a baseline foundation from which qualified professionals and organizations can perform consistently. But global standards only go so far.
 
Tufts CSDD research demonstrates that clinical trial operating efficiencies run deeper and relate to company culture, organizational structure, risk aversion, legacy, and outdated processes and practices. Together these fundamental conditions unintentionally increase costs and inefficiencies. The Re-Engineering Clinical Trials Summit explores these conditions and how organizations must manage change to arrive at a new and better development paradigm.
 
Contract Pharma: Do you find the pool of experienced clinical staff to be improved in today’s market or does it remain a challenge?
 
Peter Schüler: Engineers learn how to plan and build a bridge as part of their university studies. But, physicians, pharmacists, and nurses do not necessarily learn about the process of drug development during their university years. As a result, most enter with workforce with little experience, instead gaining that knowledge “on the job” after a few years in the pharmaceutical industry or in clinical research. To increase the pool of experienced clinical staff, university education in pharmacy, medicine and biology must focus more on fostering knowledge of drug development. Over the past 15 years, several universities established courses dedicated to pharmaceutical medicine, i.e., the science of how to develop a drug. Even though the need for such dedicated experts is still higher than the output from these institutions, there is at least a positive trend.
 
In summary
 
Brendan Buckley: New technologies, if merely added on and bolted to the outside of existing process and practice, will merely increase cost and complexity and will make investigators’ roles more difficult. When Michelangelo was asked how he carved the statue of David, he answered that all he had to do was to remove the pieces of marble that were not needed. Transformative change in drug development requires an equal recognition of what must be discarded as much as what might be added.