What did you do in the last meeting you attended? Assuming you weren’t running it yourself, did you listen to what everyone was saying? How many times did you check your email? How many websites did you visit? What proportion of the meeting would you say was important to you personally in getting your work done? I know the answers to these questions. I don’t know the answer to this one: why do we do this to ourselves?

After securing food, shelter, clothing and sex, early humankind’s next step (or detour) on the road to civilization was probably having a meeting. The next step after that was to not pay attention when someone else was grunting about something irrelevant to the next wooly mammoth hunt. Today we can look back with pride and marvel at how far we have advanced from our primitive beginnings. Now, unlike our distant ancestors, we have agendas!

I have written before about the strange rite of the weekly meeting, whose frequency is determined by an arbitrary astronomical rhythm, and not at all by a connection to the work at hand. But if meetings are perhaps inevitable, at the very least let’s pay attention! What is rampant throughout clinical development, and probably the entire pharma enterprise, is what should be called “unattended meetings.” We should suggest to Microsoft, makers of the ubiquitous Outlook software for scheduling meetings, that they add another choice to meeting requests other than “Accept”, “Accept Tentatively” and “Decline”: “Attending But Not Listening.”

This Time, Technology is Not the Answer

One thing we know, technology has only worsened the unattended meetings phenomenon. Twenty years ago the worst thing we probably did when we weren’t paying attention was to doodle (with a pen, on a piece of paper). It is technology that enables us to supplant doodling with checking, and writing, emails; surfing the web on phone, tablet or notebook; or just doing other work. Simple telephone conferencing has created the modern marvel of enabling us to not pay attention to meetings from across the globe, in real time! Alexander Graham Bell could never have anticipated such value added.

What’s the Cause?

Why are we not attending to the meetings we attend? The list of reasons is long: certainly a lack of relevance and a surfeit of meandering discussion is the first cause. But there are worse reasons, such as attending the meeting only in order to assert authority, or defend a staffer from another department, or because your company values “consensus” at all costs, or because we are afraid of being left out. Then there’s misplaced politeness, basic mistrust, and the ultimate time-waster: if she’s going to come, you’re going to come too!

One of the key motivations for attending, yet not attending, meetings is that there may in fact be a moment in that meeting – brief but critical ­– when there will be a kernel of information that actually is relevant to your work. But what a cost to get it! And what a risk that you’ll miss it, even if you are not surfing!

The root cause of this time-wasting may be that we mistake a meeting as a medium of getting information. There can hardly be a more inefficient means of sharing, getting or requesting information. Instead, this is what today’s technology is indeed useful for. Clinical development is an arena filled with software applications generating data at our fingertips. While the software might not be good at turning that data into information, that’s what we humans can do, as long as we don’t spend our time in meetings instead.

Justifiable Risk

There are really only two good reasons to have a meeting: discovery, and decision-making. Discovery is a powerful purpose; decision-making is a necessary one. A meeting for discovery is how a staff group formally explores a research or process problem; if well run, these meetings can be exhilarating, and put other meetings to shame. Group decision-making may indeed be critical, and if so, no one should feel the need to drift to the electronic ether while the decisions hang in the balance.

Short of eliminating all of the meetings that we actually do not attend, we should be helping each other scrutinize the reasons why a meeting is being called. Is it because we don’t think about the topic until we walk into the room? Is it because the way we use our technology tools is failing to inform us? Is it because we outsourced the work but can’t trust who we outsourced to? Is it because we are afraid to act on the obvious, without using a multidisciplinary group to cover our tracks? The time we are wasting is our own. No one can afford it, and we all pay for it. Let’s have a meeting to discuss this.

With the rise of mega-CROs, and the widespread willingness of large pharma to outsource clinical development to them, is there anything left for a sponsor’s clinical development group to do? Indeed yes. More than ever, there are hyper-critical functions that sponsors must execute effectively to produce success in clinical development. This can be summarized as implementing a performing process for managing outsourced development.

It is a truism that pharma “hates” their CROs, while at the same time pharma is using those same service providers more and more. The current fashion for “strategic” relationships has not ameliorated this at the operational level, although perhaps at the executive level. Much like what happened with software providers, where the failure of clinical development applications could often be traced to poor implementation by the sponsor customer, so too can frustrations with CRO performance be traced to suboptimal vendor management by sponsors. Both sponsors and their providers can benefit greatly from improved provider management, which can create a positive cycle of trust, high performance, and higher value.

Those with long outsourcing experience understand that it takes robust internal project management to ensure high provider performance. This is also true when offshoring functions. Too frequently, however, this increased oversight is not budgeted for. Most importantly, as similar as the functions of clinical operations are, whether done in-house or by a provider, the process for managing, contracting, measuring and ensuring high performance must be substantially different in the two scenarios. Again, too frequently, new processes, and the subsequent re-definition of roles and responsibilities, along with concomitant training, are not designed and implemented.

Moreover, if outsourcing was chosen in order to eliminate interdepartmental conflict, it is likely that the conflict will continue when the services are outsourced; essentially the conflict is simply outsourced along with the function. If clinical and data management mistrust each other when both are in-house, this mistrust is likely to continue if outsourcing one or the other is all that is done to try to fix it. Without open recognition of existing issues with governance, interpersonal conflict, differing philosophies (about data cleaning, about the purpose of monitoring, about the role of science, etc.), these factors – all creators of suboptimal performance – will persist and likely be exacerbated in an outsourced operational model.

How would we recognize a performing process? There are a number of indicators:

· Fewer agenda items about conflict or performance at the Joint Operations Committee meetings

· Lower staff turnover on the service provider team, and seamless execution when it does happen

· Full transparency for both sponsor and provider on the status of all trial elements (from protocol changes to deliverable delays) and on the reasons for these changes

· Fewer amendments, fewer change orders

· Both sponsor and vendor feeling safe to tell each other the truth

· Ready knowledge of which vital few metrics are important , and where “we” (sponsor and provider) stand on those metrics

· Easier contracting and faster study startup because of the trust and transparency built – not from a “strategic” handshake, but from demonstrable high performance.

We can’t successfully outsource what we don’t respect or don’t understand. The long-term danger in prolonged outsourcing is that the fundamental and critical knowledge of operationalizing a protocol will have disappeared from sponsor staff. We must be vigilant to prevent this. Active and fully funded vendor management is one step in preserving operational understanding in the midst of scientific inquiry. This ensures an environment that creates the opportunity for innovation in high performing processes and development excellence.

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.

Sometimes, when the resistance is greatest, the treasure being guarded is the most valuable.

“The path of least resistance” is a seductive phrase. It is used so often by those made nervous by change, or those who simply want to avoid conflict. It is seductive because it sounds wise, mature, even efficient. And sometimes I suppose it is. But often as not, the path of least resistance is very winding, indirect by definition, filled with backtracks, detours and roundabouts. It may have the least resistance, but sometimes it is the slowest path, without any guarantee that you won’t come to a dead end.

Boulders Aplenty

The path we take to arrive at change – in a process or strategy or the tools we use – is a key determinant of success. The resistance that we usually seek to avoid can take innumerable forms, and so these seem like daunting boulders in our way. Let’s list just a few:

§ Inertia, the immutable law that states that an employee entrenched tends to stay entrenched

§ Lack of a perceived demand for change, or “what’s everyone so upset about?”

§ Distractions, as in “I’m too busy figuring out how the latest merger affects my retirement plan”

§ Alternative priorities (“I have my own agenda, thanks very much”)

§ Compliance, as in “I’m not sure which one, but I’m sure the regs don’t allow that”

§ We have a process for that, where “process” means bureaucracy

§ We have channels for that, as in “go see the contracts office”

§ Personalities (take your pick, from passive or hostile to know-it-all)

§ And the ultimate boulder, the budget (“sorry, we didn’t budget for that this decade”).

When faced with this landscape, no wonder we typically look for less resistance, but if we try to miss all the boulders, how will we ever find our way?

Examples Aplenty

Throughout clinical development there are many boulder-strewn pathways to greater efficiency. Let’s think about just two examples: reducing source data verification (SDV) and improving protocol feasibility. First let’s look at the paths of least resistance.

SDV is a sacred cow milked by data management, monitoring, statistics and QA. And time-and-materials-based CROs endorse the labor-intensive policy wholeheartedly. The path of least resistance will lead us past these pools of quicksand on a route that nods empathetically to each of the resistant constituencies. We will concede that once you start looking at one field on the eCRF, you might as well look at them all. We will let statistics throw more queries on the truck. We won’t try fighting QA’s fears by taking the time to read the regulations more carefully. And we will give in when the CROs warn how expensive it will be if they have to change their SOPs just for us. The path of least resistance will lead us to a minor reduction in SDV, with virtually no efficiency benefit, but lots of arguments avoided.

With improving protocol feasibility as our destination, the path of least resistance will take a very wide turn around the medical affairs staff who just joined industry from academia yesterday, abdicating our responsibilities as clinical operations professionals. We will go miles out of our way to accommodate key opinion leaders essential to research paper authorship, but out of touch with patient populations and their health behaviors. And we will take the superhighway to the advertising agencies who will “rescue” our study after infeasible enrollment targets are missed.

There’s Gold in Them Thar Resistances

We cannot base our work on the paths of least resistance. Of course we want to work without acrimony, arguments, and escalations. But our industry is suffering from this ingrained fear. Complacency and inertia have led to a degree of ineffectualness that triggers executive dismissal of the clinical development function. So far, that means simply transposing the inefficiency from internal resources to external ones. A better analysis would recognize that sometimes, when the resistance is greatest, the treasure being guarded is the most valuable.

Facing the resistance should not be corporate suicide; instead it can take the lid off of hidden misunderstandings and past grudges. For instance, challenging traditional SDV policies head-on, if done correctly, generates a healthy debate that puts the issue in the context of modern realities instead of 1990’s assumptions. Similarly, maintaining weak protocol evaluation practices to protect interpersonal scientific relationships will only cost us time and money we do not have. A direct comparison of expert opinion with properly collected data on patient populations, distribution and attitudes can have a lasting improvement on clinical development performance.

If we can get past entrenched self-interests defending the current SDV policy, by confronting the boulders head on, we will discover remarkable reductions in necessary data monitoring effort. If we face the rock cliff of infeasible protocol designs at the first gate, and dare to say that climbing it is more important than ego, then we may find a much shorter path to full enrollment on the other side.

The path of most resistance may be arduous at first, but as with all pathfinding, the more we travel it, the smoother and faster the path will become.

The cost of dysfunctional relationships is very high in time, money, reduced motivation, and reduced productivity.

This column marks the beginning of a new series of essays for the ACRP Monitor entitled “Operating Assumptions.” Its focus will be on the process of clinical research – the good and the less good, the way things are and the way they should be. We will range over the broad spectrum of clinical research conduct and look at the operational challenges – tactical and strategic – that we will be facing in the coming decade.

As the title indicates, we will be targeting “assumptions,” the sacred cows of operational conduct. One such bovine is the common phrase, “it’s not personal, it’s just business,” a phrase used most often to be mean exactly the opposite (not unlike another classic, “with all due respect,” when no respect is being paid at all). Clinical operations success is all about the personal, but our skills in this arena, and our willingness to engage in interpersonal challenges, are limited.

It is Personal

Coping with the personal side of business is a daily task and the source of universal frustration. What is key to recognize is that dysfunctional people create dysfunctional processes. An analysis of poorly performing clinical research groups usually reveals an illogical or flawed process that has its roots in an accommodation to a dysfunctional key player, or flawed leadership, or fatal compromises designed to avoid political conflict.

When we say “it’s not personal,” we are trying to push away this most difficult part of our work, and we are trying to pretend, or hope, that somehow de-personalizing the process makes it “just business,” by which we mean that somehow personalities will be replaced by virtual machines. This example of wishful thinking is rarely satisfied.

Actually, it’s all personal. Let’s think about a not-so-exaggerated workday for a Clinical Project Manager. When she opens up her email in the morning she finds a hundred new email messages. Her study’s CRO project manager has changed again and she learns she has to provide an orientation to the new guy as soon as possible. Her boss returns an email she wrote yesterday, saying she is complaining too much and she should fix her problems with her CRO by speaking directly with them. QA is writing to point out how one of her studies is not following SOPs. Contracting wants her to switch CROs on her program for the next trial because they have negotiated a better deal. Program management wants her to revise next Quarter’s spend estimates.

She checks her calendar and sees that the department admin has her triple-booked all day. She looks up from her desk and some management consultant is waiting at her door for an interview she is already late for, but does not know why it is scheduled.

She goes to her first meeting of the day, a study team meeting. The clinical data manager wants to revisit the edit checks agreed to last week. The statistician is objecting to one of the eCRF designs, even though FPI is only 4 weeks away. The clinical supplies representative hasn’t been coming to these meetings until today, and now announces they can’t possibly have study drug in time. The in-house CRA, who works for her, reports that she’s been too busy and the TMF isn’t up-to-date. Her Blackberry is filling up with new emails and it’s only 9:30.

Not such a farfetched scenario, and most will say that this is just the reality of clinical research operations. But what may be behind this acid-churning hour of work? All kinds of pathologies.

Pathology is Personal

There are several common personal pathologies in clinical research organizations:

Passive-aggressive behavior. Does any of this definition sound familiar?: “Passive–aggressive behavior, is passive, sometimes obstructionist resistance to following through with expectations … marked by a pervasive pattern of negative attitudes and passive, usually disavowed resistance …It can manifest itself as learned helplessness, procrastination, stubbornness, resentment, sullenness, or deliberate/repeated failure to accomplish requested tasks for which one is (often explicitly) responsible…”

Avoidance of confrontation. For various reasons (discomfort, fear of reprimand or reprisal, corporate cultural taboo), we dance around what we want to say and never quite get the topic on the table, thus ensuring the dysfunction will occur again.

Pressure, fear, intimidation. Intertwined with the pathologies above is the pressure to perform with fewer resources, meet the trial timelines or the regulatory deliverables, and keep one eye always on regulatory compliance. The fear means we are afraid to sanction dysfunctional behavior and afraid to fire people who are damaging to the group environment. Many research managers say “it’s impossible to fire anyone around here.” Ironically, the fear factor also means we are afraid to be more inquisitive during the hiring process, which could help us avoid the dysfunction before it starts.

Conflicting agendas. If left without vocal and consistent executive leadership, various groups will pursue individual vertical goals or philosophies that clash with those of other groups. For instance, data management may assume it is the sole entity responsible for data cleaning, while statistics, CQA and drug safety may also feel equally, or more, responsible.

Obscurity and opacity. Each discipline in clinical research preserves its value and job security by speaking in its own professional language, jargon, and unnecessary detail. This enables internal and external staff to shield problems, underperformance or conflicting agendas from those who might object. It is particularly frustrating when all parties are sincerely trying to cooperate, but have lost the ability to communicate with one another.

Incompetence. I can feel readers cringe as they read that word – it is so politically incorrect. But what do we all talk about half the time? Incompetent leadership, incompetent service providers, incompetent staff, incompetent sister departments. Sometimes it’s true – they really are incompetent. And if you can’t fire them (see above)….well, talk about dysfunction!

These pathologies are ubiquitous in research organizations and yet the typical clinical operations manager or employee is not equipped with the training to recognize and improve on interpersonal dysfunction, nor do we commonly work in cultures that protect and nourish interpersonal effectiveness.

Essentially it’s willy-nilly: the people we work with like us or not, have another agenda or not, respect our authority or not. And thus our interpersonal success seems like the luck of the draw – a good boss or a bad boss, a good employee or a bad one. But leaving it to chance is very risky. The cost of dysfunctional relationships is very high in time, money, reduced motivation, and reduced productivity.

Have a Better Day

How do we fix this clinical project manager’s day? Any improvement will be a step forward, so it can be taken in pieces – how expectations are set with employees and CROs, how meetings are run (not for getting through the agenda, but for effective decision-making), writing consistency and cooperation into service provider contracts, and more. These steps may seem small, but they can have great impact.

The larger challenge is to improve the company culture. Many clinical research organizations, perhaps because they are science-based but required to be business-like, are passive-aggressive cultures. Other clinical research units, such as some CROs, are run in climates of intimidation. How do we change a culture? Company culture is a rollup of personal attributes, rewarded explicitly or implicitly over time.

Leadership can improve (if not “change”) culture. If you think you have these problems, share this column with your leadership, and start a dialogue. Be frank, which means you have to be prepared for hearing frank things in return. It may not achieve what you are hoping for, but frank dialogue will cut through the Jell-O of animosity, incompetence and obstinacy.

What is wrong with the catchphrase we started with is its false duopoly: clinical research is a business that is manifestly personal. We need to celebrate, learn about, and become expert in both. Our companies need to value, and professionalize, “the business of people” for clinical research to be a cost-effective success.