In keeping with this month’s issue on Best Practices in clinical trial conduct, the editors asked me to reflect on Best Practices in clinical development process, as seen in real life situations. Being somewhat of a non-believer in Best Practices (who’s to say any practice is “best”?, and why is someone else’s “best” necessarily best for you?), I did conclude that I could cite a number of “pretty good” process examples which are worthy of emulating by other companies. All of the following are actual examples; the company identities have been omitted to protect their competitive advantage. If we were giving Best Process Practices Awards this year, here are the winners.

Merging Boldly

Mergers are rampant in our industry, amongst companies large and small, and as far as most investors can tell, they run smoothly, even if they don’t produce dramatic improvement in the flow of new drugs. But as anyone who has been inside a merger knows, the operational impact can be devastating, and at the very least, highly disruptive. Merger failures include poor understanding of where the strengths lie in the new organization, missing the opportunity to make real operational improvements, trying to keep people happy without regard to business effectiveness, keeping unproductive functions alive, and so on.

One company took a different approach. They decided to act swiftly to analyze strengths and weaknesses in the merged operations, and where necessary, create a new organization chart with re-articulated roles and responsibilities before any final management changes were announced. The analysis was rapid but intense, and informed with extra-company experience. Major re-assignments were made, even of line managers, and in some cases new units were formed for tasks the new company would be much in need of. Instead of the usual post-merger behavior, where a company just looks at the management players and leaves the rest up to them, often resulting in years of slow, distracting upheaval, this company sought to get as much change as possible accomplished quickly. And not change for change’s sake, but change that was incisive and potentially transforming. An excellent approach to exploit the operational opportunity mergers present.

Investing in Change Governance

We have written before how critical it is to govern change effectively – that there must be empowered leadership, with money and executive backing, and an infrastructure to handle the myriad of tasks necessary to make process improvement successful. Too often in clinical development, we retreat to leaderless teams or matrixed relationships; major change is cast as an “initiative,” which leaves individuals and managers free to choose whether they will commit. And without resources, both human and monetary, even strong visionaries cannot succeed.

A large pharma introducing a major change in clinical development made a significant investment in change governance this year. They wanted to move quickly but knew this change was mission-critical and high stakes. They created a new department, which would operate globally to manage this multi-year process transition. It is a permanent unit, with permanent members formally transferred in. Former line operations staff are now fulltime change agents. Top executives are fully informed and committed to its success. The department is fully budgeted and is resourcing ahead of the curve of need, instead of behind – in itself a major accomplishment at most companies. They have sought to staff all the roles necessary for change management, from study team mentors to investigative site trainers, and they expect to achieve successful, compliant process change in much less time than most of their big pharma peers. The investment in governance is paying off.

Learning from Mistakes, Sincerely and Concretely

Many clinical development groups routinely talk about “lessons learned”; they properly seek to understand what went right or wrong with a project or particular trial, so they can avoid repeating past mistakes and remember to do again what they did right. Unfortunately, such efforts are usually little more than one long meeting, a flipchart pad full of observations, and a bunch of action items that individuals are supposed to remember for next time. Too often, the “learning” dies on the spot. There is no formal means of documenting the discussion, no one keeping track of actions taken, and no protection from that learning just walking out the door in the head of a departing employee. Worse, the learning is often incomplete: messengers of bad news are afraid of being shot, or the attempt to seek information may not be cast widely enough. Equally common is that the lessons are articulated too vaguely, in words and opinions too familiar to be truly heard or acted upon.

One biopharma with many lessons from a just-concluded pivotal trial decided that learning as usual was not enough. Instead they used a formal exercise designed to comprehensively analyze and document what they had learned about this trial’s conduct. They looked for “root causes” of problems they encountered, which enabled them to identify broad but meaningful themes whose improvement will have wide impact on future trial conduct. These root causes are actionable, not theoretical, and provide a foundation for a diverse set of clinical operations process improvement steps.

Measuring the Vital Few

We have written many times that measuring our performance can be so useful to companies understanding where and how to devote process change energies. As we have described, those companies who get “metrics religion” often go into overdrive, and end up with a vast array of data, and pages of reports, which managers ignore and staff resent. Another flaw in most companies metrics programs is a focus only on time intervals (last patient visit to database lock, for example), which are determined by too many contributing variables so as to make correct conclusions impossible to derive.

An international biopharma has demonstrated that in one area of their operation, clinical data management, they can apply metrics for resource planning, performance monitoring and technology assessment without falling into either of these traps. By focusing on the “vital few” metrics which are both reasonable to collect and have operational significance to know, they have been able to minimize the practical burden of performance data collection while increasing the usefulness of the results. As importantly, they are focusing on the units of work which best describe operations, rather than abstract time intervals. Using units of work translates much more accurately into management decision-making.

Knowing It’s Never Too Soon for Compliance

Emerging biopharmas who are just beginning to see their first drug candidate approach Phase III usually continue the pattern of operations which got them there: use a lot of CROs, focus on the science, and ignore clinical development or postmarketing infrastructure. They follow the same philosophy they followed through discovery: I’ll buy that next piece of equipment or hire that next person I need the day I need it and not a moment sooner. That strategy can work in discovery, but having the organizational infrastructure for a successful submission and postapproval support is not something one can buy in a moment – it takes time, anticipation, skill and practice

Just such an emerging biopharma has demonstrated visionary practice in its small clinical group as the company gets close to submission. They have instituted a broad and deep review of their clinical SOPs and fleshed them out in the many areas where they were thin. These SOPs also serve to ensure that their clinical program is robust right now, as they expand the scope of their candidate’s indications, instead of continuing to rely on outsiders’ standards. And they have also recognized the importance of creating a legitimate pharmacovigilance function, with the appropriate tools, so that they are prepared to handle internally the safety monitoring needs an approved drug will require. In both cases – SOPs and pharmacovigilance – the company was able to internalize a compliant infrastructure at modest cost with many long-term benefits.

Using the Right Reasons for Vendor Selection

My last example for the year’s Pretty Good Practices is a company who has gone about technology vendor selection more efficiently than most companies do, because they focused on the right reasons for choice. Instead of spending months of intense effort to develop, define and document the functional requirements for a clinical IT software application (i.e., how should the commands appear on tab 12), they recognized that this would be reinventing the wheel. Clinical IT applications are so well defined in purpose and use that developing functional requirements for them de novo is akin to specifying how a word processor should work.

This company instead focused on business requirements: that is, what did the company need from the software and its vendor, rather than how the software should look or act. They focused on the imperatives they were facing, the skills of their staff, and the financial and time constraints of their particular development program at this point in time and the foreseeable future. These characteristics are not the same among all biopharmas; indeed they can vary greatly. And having identified what was important to them, they found specific, meaningful differences amongst the products and vendors that a functional review would never have revealed.

Four Common Qualities

There are common elements in these Pretty Good Practices: boldness, speed, simplicity, honesty. These are qualities sorely lacking in most pharmaceutical development operations. When you see them, good things are likely to follow. Whether or not the specifics of these stories apply to your company at this moment in time, these qualities will always serve you well.