Because of their exclusively big-picture perspective, management tends to assume that schedule and budget problems are an
inevitable consequence of the development process. But trial budgets, schedules, and quality can be successfully managed,
if measured. Senior executives should measure scientific quality, execution quality, and the success of each protocol. They
also should set goals for execution quality and then insist on trial-over-trial improvement in meeting those goals. Management
may insist, for example, that the organization's clinical trials move from 90% late to 50% late in the first year, followed
by 25% late in the second.
2. Put one person in charge. Across the industry, no single R&D group has ownership for the end-to-end success of the clinical trial protocol. The only
sure-fire way to solve this problem is to invest authority, responsibility, and accountability for protocol success in a single
individual or group.
Many pharmas have attempted to do this, most notably by creating a protocol manager or director position. However, history
has shown that while this person ends up with responsibility for protocol success, he or she never has true authority to compel
the compromises needed to solve conflicting scientific- and execution-quality requirements. The result is that these managers
are perceived as ineffective, when in reality, they never had enough authority to be successful in the first place.
To solve the problem, companies need to appoint an individual that sits above both medical and operations experts, and who
has clear responsibility, accountability, and authority, as well as unwavering senior-management backing. This person ensures
that execution quality concerns receive the same up-front attention as is afforded to scientific quality currently.
3. Create accountability, reward success. Typically, R&D management takes an authoritarian approach to the execution of clinical trials by dictating a schedule and
budget. They set out schedules by saying things such as, "This trial needs to be completed in 18 months for $10 million."
These budgets and timelines may fit nicely into management's overall product-launch scenario, but they often appear arbitrary
and unrealistic to the folks who have to write and execute the protocol. In this way, they force the team to make unrealistic
promises, skip crucial planning and review steps, and ultimately compromise execution quality.
A better solution is to get senior management to (1) negotiate a viable clinical trial schedule and budget with the team that
must write and execute the protocol, (2) hold that team accountable for achieving the schedule and budget, (3) provide executive
support when hard decisions and compromises must be made, and (4) reward their success.
Finally, it is critical to reward those teams that bring their trials to conclusion within their agreed-upon schedules and
budgets, rather than rewarding those teams that miss their targets but then exert Herculean efforts to resolve the problems.
4. Mandate the use of new tools and processes. The typical protocol has a scientific review and a cursory enrollment feasibility analysis, but rarely anything more. Instead,
the protocol teams need top-notch tools to obtain the most cutting-edge scientific and execution quality. In particular—if
execution quality is really to be emphasized— management must supply more sophisticated tools and mandate that they be used
via a systematic development and review process.
Some of the tools that can be particularly effective at increasing execution quality include:
» Bayesian enrollment analysis conducted at the protocol synopsis stage to ensure an accurate enrollment forecast and optimized
inclusion/exclusion criteria (this helps avoid amending the inclusion/exclusion criteria later and eliminates non-enrolling
» Walk-through of the protocol at the penultimate draft stage to ensure that visit schedules, procedures, and inclusion/exclusion
criteria are in line with execution-quality requirements (this helps to ferret out execution problems that will cause data
problems and amendments later)
» Detailed, systematic, objective reading of the final protocol to remove inconsistencies, conflicts, and errors (this keeps
investigators from getting confused and making protocol errors)
» Protocol-quality checklist that provides the team with criteria for judging the quality of the protocol as they develop
it (this helps the team incorporate lessons learned from previous protocols).
In the face of time, budget, and staffing constraints, it is often convenient to skip these steps. However, there is ample
evidence that skipping this up-front work results is scads of preventable errors that later end up costing much more in schedule,
budget, and data quality.
The Way Forward