Kenneth A. Getz

Industry sponsors have long focused their attention on accelerating cycle times and on reducing drug development inefficiencies. There is no shortage of opportunities to streamline activities—from protocol design to CRO and site identification, to subject recruitment and statistical analyses—inefficiencies abound. But up until now, attention and initiatives aimed at achieving efficiency improvements have centered on activities within drug development phases. Scant attention has been paid to the breakdowns that occur as clinical data and operations transition from one research phase to the next. As such, between-phase inefficiencies may offer new opportunities for biopharmaceutical companies to accelerate drug development cycle time, improve overall performance, and lower costs.

In-between opportunities

The impact of between-phase improvements in efficiency could be substantial. Between development phases, there is no defined timeline in which key decisions have to be made. The treatment period is fixed within a given research phase. As a result, the opportunity to drive efficiency within phases is limited by the amount of time it takes to run a study.

Transition efficiencies between phases also may be easier to achieve, as they are largely controlled internally. Within-phase efficiency gains rely heavily on improvements in relationships with external service providers—a more difficult area to glean process improvements.

Based on discussions with drug development executives in pharmaceutical and biotech companies, there are three broad opportunity areas to streamline inefficiencies during phase transitions. These between-phase opportunities are inextricably linked and play a critical role in driving success within drug development phases. The three areas are:

• Decision making
• Data analysis and interpretation
• Planning and preparation.

According to the executives interviewed, transitional inefficiencies are in large part due to mistakes drug developers make in gathering inappropriate and incomplete inputs into decision making late in the process and in failing to anticipate downstream needs. Also, companies fail to build the appropriate level of internal consensus and alignment around key decisions.

"The Phase I to III mentality is a hindrance to efficiency by keeping drug developers thinking more about the means than the end," says Evan Loh, MD, vice president of clinical research and development at Wyeth. "Companies generally know the goal but fail to provide the necessary input to optimize decision making according to specific deliverables. Lacking that, companies may face an interpretation nightmare trying to decide if a compound is or is not fit to move forward."

External inputs are cited as particularly important to phase transitions. "Unnecessary delays can occur between phases if external input into decision making from scientific leaders and regulatory agencies is not sought early, when the trial is being designed," explains Mark Bach, MD, PhD, vice president of worldwide clinical research operations for Merck & Co. "If a company wants to register its drugs globally, then misunderstandings about the regulatory environments in various parts of the world can cause delays."

Several executives suggest that companies are seeking more input from and expending more time on regulatory agencies during phase transitions as a way of managing risk. "Time spent on between-phase interactions with the FDA on special protocol assessments has been escalating while the scientific advice process of the European Agency for the Evaluation of Medicinal Products continues to take the same length of time," says Alison Lawton, Genzyme's senior vice president of global regulatory affairs, global policy programs, and corporate quality systems.

A number of interviewees noted that the uncertainty around reconciling multiple and diverse scientific and regulatory input adds another element of inefficiency. "There is no commitment by regulatory agencies to offer joint advice," explains Dan Bollag, Genzyme's vice president of regulatory affairs for biosurgery. "We literally have to make a formal appeal to each agency."

Executives from several drug companies report that often their early phase studies are designed without later phase study programs in mind. As a result, frequently their companies have had to resort to modifying and expanding later-stage programs to cover for areas missed earlier.

"When it's necessary to look at Phase II results before designing a Phase III study, the key challenge is to do neither too much nor too little advance preparation," explains Bollag. "Research sponsors usually go to one of two extremes: They may not do any thinking about Phase III until all Phase II data is on their desk, or they may spend a lot of time figuring out what Phase III trial to do and implement regardless of what the Phase II data tells them."