“What are we in clinical development going to do to contribute to therapeutic innovation?”

At a recent holiday party, one of my neighbors said to me, “YOU are in clinical trials – why do they take so long and cost so much? What’s up with that?” After I explained that I wasn’t personally responsible for the state of drug development, I gave my standard answer (concern for safety, regulatory requirements, minimum drug exposure periods, hypotheses complexity, etc.), but I thought about the question later. With all the advances in science in the past twenty years, what have been the advances in how we prove drugs are safe and effective?

A simplistic overview over the past decades would conclude that there really have only been two big ideas in clinical development in this period: enabling technology, and outsourcing. Basically, EDC (electronic data capture) got rid of the paper and CROs got rid of the people. Of course, more than that has happened, as we will discuss below, but regardless, what have the results been? Fewer people, fewer companies, fewer drugs. While we are ultimately dependent on breakthrough science, what are we in clinical development doing to contribute to therapeutic innovation?

Information Technology Leads the Way

Information technology has generated considerable innovation, time saving, and enhanced analysis over the last fifteen years. EDC has been transformative, the very definition of “enabling” technology. EDC has made adaptive trial design possible, even though the concept was around for decades. EDC has altered the relationship between sponsor, sites and monitors fundamentally. It has enabled a series of related technologies to blossom (electronic patient-reported outcomes, interactive response technology for patient randomization and drug supply management) and made other technologies infinitely more practical and useful (data warehouses, clinical trial management systems, etc.).

ePRO has given us data direct from the patient which can be relied upon for accuracy and timeliness – a dramatic change. Improved adverse event systems that have enabled rapid and comprehensive regulatory filings have eliminated much burdensome hand work and improved analysis for signal detection. The electronic submission of a panoply of regulatory documents – most importantly NDAs/BLAs – has progressed a great deal from the CANDAs of twenty years ago. Sponsors now understand how to apply technology to the fundamentals of trial documents, in an electronic trial master file. Data warehousing is replacing clinical data management systems and helping sponsors grapple with the flood of new data types (images, samples, genomics data, lab data) which go well beyond simply replacing the paper case report form.

Strategy Innovation Lags Behind

But what can we say about innovation in the strategy for and process of clinical development in recent years? In particular, what can we say the industry has achieved other than exploiting technology and outsourcing the heavy lifting?

There has been no lack of concern. For years, industry meetings (and private executive discussions) have focused on critical issues such as reducing the “white space” on the timelines between one trial and another, one program and another. We have focused on the continuing, nearly unchanged dilemma of slow patient enrollment times. We have struggled with resourcing trial tasks through the peaks and valleys of clinical development pipelines. We have despaired at the continuing dilemma of study protocols taking too long to develop and changing too often once they are finally finished. But most of all we have been under constant pressure to work faster and cheaper without compromising scientific or ethical integrity.

So what have we done in response? There is not much to highlight. Investigative sites have improved their trial competency and the efficiency of their operations. We have traveled to many new corners of the world looking for trial subjects, hoping this will accelerate enrollment completion. Study designs have evolved usefully, not just toward adaptive designs, but with an eye to combining Phases, using branching protocols, and exploring secondary study endpoints as a means to do better, faster science. The “virtualization” of study teams (again enabled by today’s technology) has tried to overcome geographic barriers to hiring and assembling the best talent to manage and execute trials.

We have played endlessly with organization charts, chasing the ever-elusive answer to the question of which comes first – functional discipline, operational process, or therapeutic specialty? Having tried every possible combination with equivocal results, we should not expect an answer to that one soon.

Most noticeably, we have tried probably every possible staff resourcing strategy under the sun: outsourcing, in-sourcing, off-shoring, in-shoring, functional service providers, full study outsourcing, complete outsourcing, contract employees, and more. In the end, what we as an industry have developed as a process innovation is the concept that any and every piece of the clinical development process can be done by someone else. We haven’t innovated how the outsider does it, just the fact that an outsider is the one who does it. There is no question that outsourcing has been a huge business success – the CRO market is estimated to exceed $20 billion in annual revenues. But is it more than a shell game, moving resources using the same mediocre processes from the sponsor to the outside?

Where Will the New Ideas Come From?

Let me be clear that clinical development runs much better today than twenty years ago. We not only have technology to thank for this, but the creativity of innumerable specialists within and outside sponsor companies and CROs who have tackled specific niche problems of clinical research and improved them. We can fully expect that these incremental improvements will continue. But what will emerge as the “next big idea?”

Undoubtedly there will continue to be technology-based improvements. Perhaps putting the power of unlimited computing literally in the hands of everyone, everywhere, can be harnessed for a leap forward in the research process. Globalization (of sites, patients and scientists) will become more and more prevalent and could be more powerful than software. There are so many questions, we can hope that some of them will lead to exciting answers: How will the industry adapt to governmental and public backlash on profits? Will personalized medicine offer more than new justifications for very high prices? How will investigative sites, and more specifically, patients/trial subjects, be changed by the breadth of instantly accessible information (regardless of accuracy or relevance)? Will global economics permanently change the dynamics of the industry, governments, insurers and patients?

Meanwhile…

As we start a new year, with the challenges in clinical development only getting more difficult, what answer do we have besides getting someone else to do the work? Do we await the next technology revolution and hope those in another industry show us the way once again? Almost all change comes either as a reaction to adverse circumstances, or through the disciplined cultivation of “eureka” moments. The adverse circumstances are here now; eureka we will have to wait for. In the meantime, are we working at our tasks as efficiently as we possibly can? Certainly not. Maybe the idea, for now, is an old one: work harder at working smarter.

©Waife & Associates, Inc., 2012