“IRT needs to be considered as essential clinical research technology that is procured and implemented on an enterprise basis”

Today’s question is: do we learn from the past? In clinical research process terms, the learning seems very slow. In particular, I am thinking about information technology adoption, and today’s situation regarding adoption of IRT (interactive response technology, i.e., what we used to call IVR). Using technology to facilitate subject randomization and drug supply accountability and distribution has become an essential element of clinical operations. As more and more regulatory and sponsor attention is focused on this area, it is surprising that IRT is generally approached with two key old-fashioned attributes: it is mostly still arranged for by individual study teams (i.e., clinical personnel), and it is still mostly delivered under the complete control of outside vendors. Both of these characteristics are antique in the twenty-first century world of clinical research informatics, of which IRT should be a part.

Briefly put, IRT needs to be considered as essential clinical research technology that is procured and implemented on an enterprise basis, just like electronic data capture (EDC) and clinical trial management systems (CTMS). The history of these two earlier technology adoptions teaches us that sponsors suffered (and suffer still) from poor strategies, low process comprehension, and underestimated techn0logy implementation efforts. IRT implementations in 2013 need to benefit from these experiences. Learning from the past, we need to get it right the third time.

Not Again!

We can see the same mistakes being made with IRT as were made with EDC and CTMS to a remarkable degree. We may observe that there is an inevitable arc to technology maturation but it would be unwise to take comfort in that. The pace of quality and compliance imperatives is much faster now than in the ‘90’s, and we should not be satisfied to watch IRT mosey along.

EDC and CTMS also started as technologies selected by individual study teams, with different vendors and processes used from group to group and year to year. Being new to the technology, sponsors accepted what the software vendors told them about how best to use it, and willingly paid the vendors to do the then-mysterious steps of design, configuration and programming necessary to get the tools to work for them. Sponsors were at the mercy of vendor quality, vendor schedules, and vendor opacity. Sponsors had to adapt their processes to the vendor, and had to trust whatever training and help desk services the vendor offered would be sufficient for their sites and staff. With so little internal focus, the fact that these technologies required internal change management was simply not recognized or prioritized.

All of these factors created considerable inefficiencies in EDC and CTMS adoption, created widespread user confusion and frustration, and undermined the benefits that were supposed to be derived. Sponsors generally have fixed these problems now, after many years of hard lessons learned. Thus it is sad and surprising that the above paragraph can be applied to IRT use today. Why is it important to treat IRT as an enterprise tool and apply comparable rigor to it? The answer should be obvious to all, and yet the dilemma is that randomization and drug supply optimization have been sequestered on the clinical side of the fence, away from the data folks who traditionally handled EDC, or the informatics folk off to the side. As with all clinical research technology adoption, it is only the occurrence of compliance audit issues that has triggered even the recognition, much less the action, that IRT perhaps should be addressed in a more organized fashion.

Key Points of IRT Failure

The risks of IRT failure should be apparent: one line off in a randomization table can trash the study data. Errors can lead to unintentional unblinding. Treating randomization and drug supply issues simultaneously (with the same technologies, vendors and internal staff) can hopelessly muddy the correct processes. And as with many clinical research technology issues, confusion or disagreement about internal governance and responsibility prevents a timely solution.

Unfortunately, for the most part, IRT technology vendors have presented IRT to their clients in an overly technical fashion, which has confused clinical personnel’s understanding of what configuration settings mean and what the system will do. The older vendors also have a deep vested interest in labor-intensive opaque processes. This has compounded the lack of knowledge at many sponsors about the inner workings of IRT, what it is capable of, and what it should not be used for. The danger is that misunderstandings on both sides of the vendor/sponsor aisle are only realized downstream, when people actually begin using the system.

Factors that have contributed to this are as follows:

§ Extremely long and overly complex system specifications that are more technical in nature than user-based.

§ “Scope creep” on the utilization of IRT for data capture that would be more appropriately handled in other systems such as EDC.

§ Not having a clear picture of the intended final product until just before first patient in (lack of visualization during the development process).

§ Treating each new trial as a custom build (usually caused by out-of-date technology and financially beneficial to vendors).

§ Lack of centralized expertise at the sponsor that can speak to all of the primary components of IRT, medication dispensation and management, randomization and stratification, and unblinding.

§ Overly complex protocols which are extremely difficult to implement at the operational level.

Getting It Right

Each of these points have clear solutions. It starts with clear delineation of responsibility among the various departments involved and a singular focus of governance. Sponsors should consider IRT as another enterprise research technology and select it, design processes, and manage the change accordingly. Vendors have to recognize a new, leaner model of providing service or face being iced out by newer and more nimble competitors with superior technology. Sponsors must consider the impact of their protocol designs on the IRT arena as they are starting to do with EDC or eCOA. There are technical and tactical improvements that can improve the IRT process once better roles and tools are in place. All of this must start with a much improved understanding of IRT among clinical staff.

What are the business consequences of ignoring how IRT is used in our companies today? They will likely include embarrassing audit findings and trial delays. What are the personal consequences if we screw up again? The baseball metaphor would be “three strikes and you’re out.” Much as I love them, baseball metaphors don’t always apply to business, and sadly, since no one in clinical research ever seems to be held accountable for process failure, it is likely that no one will lose their job over an inefficient IRT implementation. Let’s think positively: another saying is “third time’s a charm.” We can only hope so.

“Fixing operational problems in clinical research, regardless of their cause, will usually end up requiring a discussion that we are trying to avoid.”

We humans are a mostly affiliative species. We like to be in groups, we like to do things together. In order to do things together, we have to get along. We all know how well people get along with each other – of such stories history is made! Corporations are the ultimate business expression of affiliation, and so they are the ultimate environments for people trying to get along. Most operational process problems in clinical research can be traced to people not getting along, for many reasons ­– philosophical, psychological, scientific, interpersonal, uninformed.

Fixing operational problems in clinical research, regardless of their cause, will usually end up requiring a discussion that we are trying to avoid, because of the inherent disagreement in the topic, or personal antipathy, or a power differential. These are difficult conversations to have. We avoid them for a short-term gain in affiliative peace. The long-term cost is a problem left to fester, a reinforcement of unproductive relationships, a solidification of the intimidation of power. In such an environment, true improvement is very hard to achieve.

Conversations Left Unsaid

There are dozens of conversations we should be having during the clinical research process that go unspoken:

§ How do we tell the sponsor physician that the key opinion leader is a lousy recruiter?

§ How do we call the bluff of the manager who says he “welcomes change” but never implements any?

§ How do we get the CEO not to promise a trial start date to Wall Street that is operationally impossible to meet?

§ How do we tell Quality Assurance that their interpretation of the regulations is incorrect?

§ How do we tell an employee, or a peer, that they aren’t good enough at their job?

§ How do we tell the functional director that sending a powerless representative to our meeting in her place is a waste of everyone’s time?

§ How do we tell the data management standards committee that the need for flexibility is more important than blind adherence?

§ How do we tell the boss that the process improvement project is a waste of time because we know she has no budget to implement the recommendations?

§ How do we contribute an honest “360-degree” performance review on our peers without having it backfire?

§ And most fundamentally: how do we call someone out for not doing what they were supposed to do?

I am sure you can supply your own examples. What is happening in each of these cases is that someone is failing to execute their work properly, affecting all of those around her, and yet we enable this failure by being afraid or embarrassed to try and do something about it. It is directly analogous to “enabling” an alcoholic.

Difficult Consequences

Unfortunately, there are very concrete consequences to our avoidance of difficult conversations. Let’s take a complex, real example which at first glance seems unimportant but which has considerable consequences: A study is in startup mode with a clear sequence of events, some of which include: finish the protocol, send it to the various site ethics committees (ECs), build the electronic case report forms (eCRFs) in the meantime, certify the sites’ knowledge of the trial software, distribute study drug, start enrolling. But what if one sponsor physician on the project insists that for marketing or professional reasons, Site “D” must be one of the first enrollers, and that Site is in a country that requires final eCRFs before EC approval. As we know, that interrupts the carefully planned, time-pressured startup sequence. To wait until final eCRFs are ready, and then wait for Site D’s ethics approval, will ruin the study timeline – but the study physician insists and he’s backed by his management.

A difficult conversation is required. The study manager (or worse from a political standpoint, the data manager) has to explain the timeline change and suggest letting Site D start enrolling later. In this example, no one on the operations side felt they could confront clinical affairs with this reality without being punished for not “helping the team” by “taking on the challenge.” Instead the corporate culture expected the operations team to perform their now customary heroics to cope with the site dilemma while preserving the timeline.

The consequences of avoiding the conversation are far-ranging. The study physician feels vindicated and immune from censure. The data manager feels de-motivated by the thought of the perpetual heroics required of her. The study manager quietly seethes and seeks a future opportunity to get revenge. All of these are the seeds of inefficient clinical research.

How We Can Talk

Some may despair at having difficult conversations, and some may shrug. Look at the power differential, look at the interdepartmental antipathy, look at the personalities involved. Shrugging or despair is not enough. The consequences on performance are too dire. While operational accountability has been loose for many years in our industry, this is ending rapidly. Inefficiency will mean your department ends up outsourced and your job (at sponsor or CRO) will be in jeopardy. In the long run it means foregoing clinical programs that may improve our medical care but we cannot afford to complete.

There are a few, challenging ways to have difficult conversations that may get us out of these situations:

§ Be courageous. Simply said and hard to do, but many situations described in clinical research operations can and are defused more easily that we expect – it just takes the courage to start the conversation.

§ Once engaged, depersonalize the situation, especially where the history of antipathy overshadows all. It’s not about what he or she said to you yesterday or last year, or what seems unfair, or what you think your career needs. It’s about the work, the study, the science.

§ Gather and focus on the facts. In all difficult conversations, the facts get lost in the power or the feelings or the legitimate stresses of time and money. Ignore these, and focus on facts that are indisputable and well-articulated.

§ Employ a work process that neutralizes the power differential, and actually makes difficult conversations routine. There are basic process designs that are intended to specifically overcome these difficulties.

§ And do not overlook the need for executive commitment to a culture that is both safe and efficient – safe for staff to challenge each other and those in power, and where staff are sincerely empowered to root out inefficiency.

Lots of things are difficult. Mostly we need to do them anyway. It is the responsibility we inherit to live in the remarkable society humans have created.

The first thing we do, let’s kill all the lawyers. – Wm. Shakespeare, Henry VI, Part 2, c. 1591

…And the procurement officers and outsourcing managers, while we’re at it. – Clinical Research Executive (Anon.), c. 2012

Professionalizing the contracting process in clinical development has gone astray. What was once meant to add a little bit of needed legal-oriented skill to project management has become a self-perpetuating web of complexity.

Here’s a true story: we were interviewing various managers of a sponsor’s clinical research department, exploring their skills at outsourcing. The departmental lawyer, the procurement officer, and the strategic outsourcing officer each said that s/he was the only one who was protecting the company from financial ruin, compliance risk and regulatory sanction. Not a single clinical person had the arrogance to assert such importance to the clinical research success. How did we get here? When and why did clinical trial expertise get so buried under layers of bureaucracy of our own making?

Every sponsor I visit has such a story. These days the stories are told as muted rumblings: monitors who report investigators furious at the site contracts sent by the sponsor’s legal department, trial schedules with built-in 3-6 month delays to allow for “CRO contract negotiations”, trial managers throwing up their hands at having to use the same CRO that failed them last time because “procurement likes them better.” Sometimes the storytellers don’t even sound like they are complaining – is this a sign of healthy acceptance, a sign of despair, or is it that no one remembers when life was easier?

When Bad Things Happen to Good Ideas

The overlapping sponsor roles of contracting/legal/procurement/strategic outsourcing all grew out of the rapid growth of CRO usage starting over ten years ago. This trend, combined with increased trial complexity, regulatory scrutiny and budget pressures, led first to a professionalization of Clinical Operations, which took responsibilities away from medical leadership, mostly appropriately. Clinical Operations diversified and specialized rapidly, and soon it was felt that study managers had too much learn, to much to be expert in, too much to handle – again, probably appropriately. One of the identified specialties was how to contract with the proliferating third parties.

But somewhere along the way, those who were supposed to advise study managers in contracting, and advise the enterprise in broad-based improvements such as standard contract terms and volume discounts, became in charge of these key elements of trial conduct. Indeed, at some companies they have become virtually in charge of the trials themselves, as a side-effect of negotiating with those who now actually do the trials (the CROs and sites, instead of in-house staff).

For instance, some companies report the procurement people now have more to say about which sites should be used than the clinical staff. While I am the first to criticize clinical managers for continuing to use under-performing sites because they want to use key researchers or long-time friends, it is no better to have procurement staff decide which sites to use on the basis of ease of negotiation or compatible liability clauses. One group should be advising the other, while the other actually decides. Now let’s see, should that be the outsourcing department or the medical director?

Professional procurement was intended to improve Clinical Operations management skills. But lawyers don’t manage trials and they don’t improve CRO relationships, although they can make them worse. The inappropriate empowerment of legal-oriented staff has introduced consistent and costly program delays; their issues can be an enormous time sink. Even the value of standardization is diluted by a level of inflexibility that is now getting worse and worse in sponsor contracting. And make no mistake: poor contracting experiences lead to poor vendor/site performance. This is strongly aggravated by the now common gamesmanship of sponsors delaying payments: poor payment performance starts site performance on a downward spiral. What was supposed to help is now aggravating and delaying the work. And the work, lest we forget, is drug development, not shiny and polished contracts. It is about good conduct practice, not good contract practice. It is, in fact, about people, not bid grids and invoice templates.

There is an assumption that contracting staff are better, indeed necessary, to create good arrangements with CROs. The thinking is that research doctors are not good managers, that individual project managers will only serve their self interest and not the company’s, and that the art of contracting is so arcane as to be unteachable. I think this assumption is abetted by both parties: study managers are happy to have one less thing to do and procurement staff want to perpetuate an aura of indispensability, as anyone does. But regardless of whether these are accurate assumptions, what was the purpose of this assumption? What was the problem we were trying to solve, and did we solve it, or did we solve something and create another problem? The solution has grown out of proportion to the problem.

Going back to our earlier example, one of the assertions of procurement indispensability is risk aversion – that we have professionalized risk management in these staff and so that is where protection lies. Generally speaking, risk aversion in this particular area of research is overkill. Site and CRO performance is not dictated by contract terms, but rather only by the skill with which Clinical Operations managers (people, not paper) learn how to monitor, measure, communicate and hold accountable their service providers. Contracting per se does not lower risk, people do. I remember long ago, my first corporate lawyer wisely advised me that if I ever actually needed to use one of his contracts to confront a business problem, I had already lost half the battle.

When Good Things Happen to Bad Ideas

Here’s a way to change the suboptimal status quo for the better. We need to vastly reduce the procurement/contracting/outsourcing infrastructure created in clinical research and instead rely on a handful of expert advisors who work with those who should be in charge: the clinical research managers. In this advisory role, procurement and legal experts can advise on the topics of good contracting, standardized terms, possible volume discounts, metrics and penalties. This advisory role, instead of a controlling role, is where the legal profession was always meant to be. It will keep us focused on executing clinical trials instead of executing lawyers, as Shakespeare would have it, while improving the relationships among the essential parties in conducting clinical research.