Whenever something is wrong, something is too big. – Leopold Kohr, The Breakdown of Nations

Size does matter when it comes to optimizing clinical development, but perhaps in ways we don’t expect. Certainly few in the clinical research industry seem to believe that “small is beautiful” anymore. Mergers of large pharmaceutical companies seem to occur monthly. Acquisition targets now even include large biotechnology companies, creating ever larger entities with contrasting cultures. The mergers and acquisitions continue despite producing equivocal benefits. The usual explanation is that somehow a larger mass of researchers will be (this time) the “critical mass” that will produce results. Meanwhile, CROs are, as usual, mimicking their customers, and so they too seek to grow as large as they can. They argue that being “global” (i.e., big and broad) is equivalent to providing the best service. Neither of these assumptions are absolutes, and there are good reasons why they should be re-examined.

Large Can Be Pretty

Merged companies usually merge their individual internal functions. So two monitoring groups become one, two data management groups become one, etc. Why? Well, either it is assumed that one department is more efficient to maintain than two, or because one company’s department is perceived as a better performer than the other. Ideally, a smaller proportionate overhead (so-called “non-performing assets” like trainers and standards/quality assurance personnel) is needed for the larger group of “deliverable-performing assets.” Each company’s methods can be examined for what seems to be more efficient, and these “best” (or better) practices can be applied to all.

Merged functions are also assumed to be more fungible (i.e., interchangeable, providing more flexibility in assignment). In this perspective, more personnel are always better than fewer. More people mean it is easier to respond to boluses of work or new initiative. More people can mean more time for process improvement because there are more “idle” hours to spread around to work on such initiatives.

Large is also assumed to be required for trial execution globally. And all trials are trending larger as we know, for various regulatory and scientific requirements, so we must be larger to respond and support. The large CROs base their business model on scale, and in fact do win a lot of business on scale alone.

And Ugly

While large means fungibility, it also means mediocrity, by definition. Why? Because of the inevitable human bell curve. The abuse of school grading (where a “B” is the new “C”), and Garrison Keillor’s Lake Wobegon (“where all the children are better than average”) notwithstanding, in real life if one gathers a large group of people together — be they the proverbial “man on the street” or all university-trained statisticians – the bell curve will apply, especially as the sample size increases. The more people, the larger the middle of the bell, the larger the pool of mediocre, or “average” talent. It’s not possible to hire a hundred outstanding data managers, or three hundred outstanding field monitors. For all sorts of reasons: vetting, timing, training, integration, consistency, quality control, motivation, life circumstances, instincts, etc. Nor, for the same reasons, is it possible to train them all to the same point of excellence, despite many companies and vendors assertions to the contrary.

Of course, large also exacerbates the extended litany of human foibles: bureaucracy, hierarchy, misunderstanding, mis-communication, mistrust. And large runs counter to the general corporate trend to minimize or reduce overhead, especially facilities. This in turn drives large organizations to geographically disperse, encourage working at home, and ultimately to outsourcing. Each of these in turn creates new dilemmas.

Let’s take a typical example of the impact of CRO scale on the quality of their services. First, all research sponsors have their tales to tell about mediocre project managers, who turn over inordinately. The big CRO has lots of project managers to throw into the fray, but a sponsor does not benefit from volume, only quality. And if a sponsor chooses to rely on a large CRO for a large trial it is running, precisely because of scale, and then learns that the CRO project manager is actually working from home a dozen states away from the sponsor and the rest of the CRO team, what advantage did we get from scale, from large size?

Small Can Indeed Be Beautiful

It may feel like scale is a necessity in today’s global research enterprise, but it should not always be considered an advantage. Indeed, some of the best industry operations examples are small, sometimes referred to as “skunkworks,” which live inside large organizations.

Why is small better? A number of reasons:

• A better environment to get the most out of individual talents

• Creates a group which is more unified, dedicated, and motivated

• Provides otherwise “silo’ed” specialist professionals with a common purpose

• Enables the goal to be “within sight,” leading to interim, achievable victories

• Easier to control

• Easier to prevent mediocrity –the bigger the scale, the more certain the bell curve rules.

One of the truisms of a career in pharma clinical development is that so many people can go through their entire working history and only touch on a series of compounds or devices passing by. And as functional groups get bigger, roles within the function can get ever more specialized, further reducing the scope and sense of ownership for each individual. Smaller functional groups help preserve a breadth of professional contribution, and can be structured so that it is more likely the staff will see a candidate through the end of clinical development.

The Best of Both

It is very important to emphasize that pharma can and should structure their development organization to gain the best of both large and small models. A key component of this is the misunderstanding people have in reacting to words like “standards,” “innovation” and “scale.” These do not have to be incompatible concepts. While we associate “standards” with large bureaucracies, and “innovation” with small teams, we can definitely have both.

Innovation can operate within standards, especially those established primarily as professional foundations, which is what most clinical development folks mean by “standards”. And of course ultimately, the regulations are the ultimate common standards that we all must live by. Even within our highly regulated process, innovation can and does flourish, if the opportunity is provided. Most importantly, small scale does not require loose standards in order to be effective. In fact, standards and other controls free the small group to focus on their output and not their process or compliance.

Nor does small have to mean inefficient. Using the principle of core functions, one can maintain professional and process standards as much as desired across the company, thereby ensuring consistent use of methods known to be optimally efficient in your company. A functional core is not a silo under another name; rather it is a professional development center which provides the time and place for standards creation & maintenance, and a place for common training and professional development. This provides two additional key benefits: it addresses the concept of fungibility without mediocrity, and it provides employees a familiar professional identity that will mean “security beyond the team” during their career.

E. F. Schumacher wrote what was then a landmark book, in 1973, called Small is Beautiful. Among other nuggets, he memorably and presciently wrote:

The most striking thing about modern industry is that it requires so much and accomplishes so little. Modern industry seems to be inefficient to a degree that surpasses one’s ordinary powers of imagination.

This certainly strikes powerful echoes for clinical development, more than a generation later. For a large organization to work, according to Schumacher, it must behave like a related group of small organizations. Interestingly, the title of his book was in turn a quote from his teacher, Leopold Kohr (quoted at the beginning of this column), who went on to say:

It is because human beings, so charming as individuals or in small aggregations, have been welded into overconcentrated social units.

Large or small, size does matter. And what matters most is whether we are managing correctly to the size we have chosen. Functional managers personally face the challenge of making the choice succeed. In the end, small may indeed be beautiful, and should be tried more often in clinical development.