Consensus is a false god and a time sink.

We all work in increasingly complex research communities, and it is not getting any easier to get things done, despite heightened urgency, potentially plentiful resources, exciting scientific advancements and loads of talented people. Middle and senior managers are tasked with moving their organizations to get things done – faster, cheaper, and always with uncompromised quality.

If only it was as simple as this diagram suggests!

Complex to Simple

Complexity, by its nature, takes many forms. From a management perspective, complexity is contributed by upper management pressures, responsibilities to your staff, the uncertainties of clinical research itself, the unknowns we are trying to discover and then overcome, and the interdepartmental, inter-company collaboration which is increasingly the norm.

The complexity you face is probably not your fault personally, but we do make it worse. We contribute to it by how we react to it, and how well (or not) we understand it. It is only going to become more common, so learning to embrace it, and to simplify it, will greatly benefit your organization and your career.

Histories and Personalities

Organizations have histories and personalities, strengths and fears, just like individuals do. This is so important to recognize, because just as we are influenced by how we handle things, and what has happened to use before, so do companies. Sometimes we call this “culture,” and too often our scientifically trained minds wander when we hear that. But in our increasingly interconnected and interdependent approach to Clinical Development, we are entwining histories and fears and personalities. For instance:

• Your research partner had a 483 just last year, but you never have.
• Your CRO is a big advocate for using the latest technology, but your company had bad experiences ten years ago.
• The little biotech you bought has been obligated to work fast, decide fast, and can’t afford to think about it, but your value is in your maturity and experience to inform and evaluate their thinking.
• Your research partner has dozens of products to develop, manufacture and sell, but your whole world is this one candidate you brought painfully into the clinic.
• Your CRO’s business model is completely different from yours, and this is compounded by four additional niche service providers who you need but don’t trust or understand.

Embracing & Understanding Complexity

 Our complex organizations and relationships in Clinical Development cry out for strong effective leadership – that’s you! That leadership you exhibit must embrace and understand the complexity. Understanding starts with:

• What are the stated Key Business Drivers for the organization and how does your work demonstrably contribute to them?
• What are the unwritten power relationships in your organization?
• Who is doing what, when? – where are the overlaps in responsibility and accountability, and how may are they competing or contradictory?
• Where’s the money and who controls it?
• How can you exploit peer self-interests, instead of only being frustated by them? Can you understand their personal and departmental professional and financial incentives?

Don’t Just Cope, Simplify

 Complexity is Clinical Development has been sneaking up on us for decades, like the proverbial lobster slowly boiling in the pot. Since we all still have our “day job”, all we often have time for is coping:

• Firefighting the day’s issues
• Accepting compromise and suboptimal performance
• Protecting core interests and budgets
• “There’s always next year….”

But there is a more productive use of our time and skill – to recognize the complexity and actively seek to simplify it. For instance:

• Overlapping accountabilities can be split up & apportioned for mutual benefit, so that everyone has a piece of success.
• Look for the facts in a given situation, and leverage it to overcome political or personality obstacles.
• Remind peers & superiors that you all have common purposes.
• Exploit power discrepancies appropriately because you are in the best position to recognize how to appeal to all points on the circle.
• Most importantly, seek commonalities rather than

Consensus is a false god and a time sink. We use it because we think it leads to political correctness, as if that was key to productivity or efficiency or progress. It is not important to sit in a room until everyone agrees on something. But it isimportant that we get most people to recognize what they have in common, and how what they are going to do will serve that.

“But It is Complex….”

Some readers, and/or some colleagues, may object to this approach thinking it is minimizing the technical, scientific, financial and interpersonal obstacles to Clinical Development today. This is understandable but doesn’t lead anywhere. Reassuring ourselves that our work is difficult is only slapping our egos on the back. Of course we need to ensure nothing important to patient safety, or colleague respect, or financial viability is tossed under the bus in our desire for simplicity. But there is a broad middle ground to operate in to improve our focus.

Focus Focus Focus

Having and maintaining focus is the key to managing in a complex organization and reaching your goals within it. Trim the to-do list, trim the cross-project links, trim the Inbox, and trim the promises you and your staff make to others. By focusing on agreed-upon priorities, and only those priorities, you can achieve a series of victories which will create progress, and positive momentum. You can create your own positive feedback loop.

If something is intractable, move on to a parallel shared point of focus. If something new looks more attractive, think long and hard about changing direction – can you finish something on your current work before switching and moving on? If you demonstrate you can be successful, more trust and virtual power will flow to you: most everyone wants the complexity simplified, unless they are hiding poor performance underneath it.

Your organization will be excited that progress is being made, and they will understand what and who was the catalyst. Be the catalyst that simplifies complexity, and everyone will reap the benefits.

“Progressive improvement beats delayed perfection”. – Mark Twain

Churning and Aligning Instead of Doing: Operational Inefficiency in Clinical Development

Steve Shevel, Senior Associate at Waife & Associates, Inc. writes…

Just the other day I was talking with an old friend and the conversation came around to the question of why people involved in clinical development are so busy all of the time?   We went back and forth on some of the usual theories, such as, too many meetings, too many conflicting initiatives and working within the confines of a regulated environment.  But, after much discussion and debate, my friend proposed a very simple but insightful theory which consisted of two principal observations of corporate life:

• We are different people.
• We almost never do anything alone.

This may be self-evident, but the implications are often overlooked and undervalued in addressing the inefficiencies and churn encountered in moving along the clinical development timeline.

My friend gave me a very salient example to illustrate his point:  His company has been discussing the use, and implementation of, Real Word Data (RWD).  After numerous phone calls and meetings, aligning everyone simply on the definitionof Real World Data was still elusive.  We discussed many possible reasons for this churn (and delay in forward progress).  I wondered whether our analytical natures (so integral to drug development), combined with our egos, intellect, need for affirmation, and etc., actually impede operational efficiency and progress.  We rely on these very same qualities to spur innovation, and yet they may be the culprits that prevent us from effectively executingon that innovation.

When reflecting back on my time working in the corporate world and my time consulting to it, it becomes apparent to me that what takes up the most time in any initiative is not the “physicalscience” (the action itself) but rather the “socialscience” (the act of engaging your colleagues and peers in deciding what action to take).

For example:

• Consensus, or at least a mutual agreement on how to proceed, is a paramount value in biopharma organizations.
• Interactions with our colleagues and peers are often influenced more by allegiances and biases then by what is best for our company.
• The circuitous trap that there may be multiple answers to any given question and wanting to explore all available options before deciding on the “best” one.

Clinical Development is complex and the companies that work within this field are filled with intelligent, passionate and innovative people, all with their own ideas, opinions and agendas.  But we should ask ourselves if we are making the operational aspects of clinical development so complex for the right and necessary reasons?

Drug development is, by nature, a slow process and that protracted timeline has contributed to our lack of urgency and our willingness to tolerate delay since the negative feedback for that delay is not immediate. Some may suggest that because we are impacting the health and lives of people, this level of caution and re-thinking is warranted. This is a valid argument for the science, but maybe not so much for the operational aspects of how we execute on the science.   The reason why managers’ calendars are so crowded is because they are spending most of their time talking to, convincing, and aligning people on how to move initiatives forward.

Interpersonal inefficiencies are not something AI or any new information technology will completely solve, as those innovations are more likely to disrupt only the transactional tasks as opposed to the social paradigms, while creating new, as yet unknown, consequences. And yet industry attention is always attracted to the impersonal (and therefore easier to contemplate) promise of technical progress.

We continue to lag behind the pace of physical science with concomitant innovation in the social science of our workplace and processes. We will need both to truly innovate and improve drug development.

Virtual Clinical Trials Reality or Just Virtual Reality?

Approximately two years ago I was attending the plenary session of an industry conference where the speaker was a representative from the FDA.  After his talk there was the standard question and answer session and one of the audience members asked him how the agency viewed the veracity of “virtual trials” in support of NDA submissions.  I watched with interest as a veil of confusion descended over the speaker’s face as he requested additional clarification on the meaning of virtual trials. After some back and forth, there was a rudimentary explanation about conducting research outside of the investigative clinic, and his response was essentially to re-affirm the required involvement and responsibility of the investigator in seeing the research subject and then he quickly moved onto the next question.  The inescapable irony of all of this was that the program for this conference, as well as many others that year and in years to come, was riddled with the topic of virtual trials, how to run them, and anecdotes of pilot programs.

The term “virtual trial” has now made its way into the lexicon of contemporary buzzwords in the clinical research industry and in doing so, has perhaps muddied the waters as to the meaning and intent of what companies are actually trying to accomplish.  My colleague Ron Waife has often stressed to me and others that “terminology matters”, and in this case it is especially true.   Thus, it may be helpful to deconstruct the terminology from the intent, and then re-brand the outcome, so as to better discuss the definition, advantages and regulatory perspectives of this important trend.

Patient Recruitment & the Virtual Response

If you ask managers at most biopharma and device companies what their primary challenges are in conducting clinical trials, the one that consistently boils to the top of the list is patient recruitment.  That is, finding good study candidates in a relatively short time.  If one delves further into the challenges surrounding patient recruitment, much of the research performed to date points to two significant factors that directly influence enrollment, namely:

1) Protocol complexity

2) Subjects’ geographic proximity to study sites.

The intent of “virtual trials,” among other imperatives, was to address both of these concerns, especially the second one, by facilitating study visits either in the patient’s home environment or at a nearby “virtual” location by leveraging the use of telemedicine technology and third-party healthcare providers.   The suggestion is that by making the experience more convenient for a subject, we can increase their willingness to participate in a trial, even one with more demanding procedures.   And this is where the “virtual” terminology becomes confusing and problematic, as there is nothing “virtual” about this interaction!  Someone who works for a company that provides this type of remote visit service recently used the term “decentralized trials”to describe the approach, which I think is a more accurate term.

There is real credence and value to a decentralized trial, especially for certain visits which only require that rudimentary procedures to be performed, and a number of companies are racing to fill this need, as the evolution of technology and remote capabilities has far outpaced the regulations that were put in place many years ago. The problem is that when we use the term “Virtual Trial” with regulators, a cold shiver justifiably begins to descend down their spines as they envision a situation where investigators never actually see or interact with subjects and physical clinics are non-existent, or worse.

Virtual Trial as in Something Else Altogether

What if there are no subjects or investigators at all? A number of talks and articles have been presented advocating for these types of trials, where the entire trial is conducted within an artificial intelligence program that promises to leverage “real world data” to predict the safety and efficacy profile of a molecule by simulating how the human body would react.  This illustration is probably a more accurate use of the term virtual, but it is very different from our previous example, and while innovative in its purpose, poses a significantly higher hurdle to acceptance by any regulatory authority, especially for a new drug/device/biologic application.  The hurdle is justifiably high since our knowledge of the human body is still so insignificant after all these millenia, as the CEO of Novartis, Vas Narasimhan, recently opined at the JP Morgan conference: (https://www.forbes.com/sites/davidshaywitz/2019/01/16/novartis-ceo-who-wanted-to-bring-tech-into-pharma-now-explains-why-its-so-hard/#28569fec7fc4).

So, it is safe to say that we are not yet at the stage where “deep learning” or AI is going to impute for us the complete metabolic impact of a particular drug or biologic, based strictly on existing EHR and other real-world data.   In fact, the entire premise of AI is that it needs to have clean structured data in order to learn from, and with such large gaps in our understanding of current human physiology, the existing datasets are not complete enough to fill in those gaps.

On the other hand, there is significant advantage and value to the concept of decentralized trials, which with continued efforts and innovation, can result in greater access to patient populations in need of new experimental treatments.  This remote model may also serve to decrease the non-safety related dropout rates from clinical trials as convenience factors are improved.

Instead of hamstringing ourselves by using equivocal buzzwords, it may be worthwhile to consider using definitive terms to explain the concept of conducting clinical trial visits outside of the investigative site. So that we have more time to focus on the perceived benefits of non-traditional trial designs and methods. The German philosopher Arthur Schopenhauer probably said it best: “one should use common words to say uncommon things”.

Contact Steve Shevel, shevel@waife.com, to discuss this further.

The drug development process by its scientific nature is one which is closely controlled, informed with rigor and volumes of data. But there is an interesting bifurcation between the research (in vitro) phase and the clinical (in vivo) phase. We can and must carefully control the first stage, but when we move to administering new drugs to humans, we enter the enduring mystery and variability of biology and environment. In human trials we have to let our discovery go off into the world, like a child sent to college on her own. What happens next we cannot control – we can only observe, record and analyze.

Our business lives and dies on the results of these clinical trials we have so little control over. But there are aspect of this stage which we dohave control over: the processes and infrastructure in support of the trials themselves. An yet most companies ignore or are unaware of this opportunity. Yes, everyone is busy running the current trial; yes, we need to get more patients enrolled more quickly; yes, we need to organize the next investigator meeting; and yes, we need to make sure that documents are being collected and data is being cleaned.   But meanwhile we may be missing a very real opportunity to address the one thing that we can control, and that is the process of how we go about executing any one, or all, of those workstreams. 

Clinical trial process optimization is often recognized as a need but rarely prioritized. Executive management is hesitant to assign resource time and budget to these initiatives in the midst of a clinical trial for fear that staff will be distracted and the trial progress will suffer. Additionally, initiatives for optimization are not milestones that can be advertised to Wall Street as progress, and so they end up being assigned to the “nice to have” category on the priority list.  Middle management may have the vision and energy to spearhead these efforts, but without strong executive support their efforts usually fall short, since the task remains subservient to a multitude of other trial-related needs.  Unfortunately, this lack of priority leads to failure, and with each failure comes a negative psychological bias and associated fatigue around operational improvement which directly impacts any future initiative.

The irony, is that assigning meaningful resource and budget to the process of conducting clinical trials and how the organization is structured to support those trials, is something we can in fact controland those efforts will have a direct downstream impact on the tangible, reportable outcomes, such as:

• Collecting and analyzing data more quickly
• Helping improve enrollment
• Increased productivity
• Avoiding duplication of effort
• Effective scalability and consistency
• …and more.

Often our industry uses the excuse that we work in a highly regulated environment and that this is the reason for our lack of innovation in trial operations or how we adopt new technology.  In the past this may have been understandable, but the regulatory agencies have recognized the importance of streamlining the drug/device/biologic development process and are in fact encouraging companies to become more efficient.  In fact, departing FDA Commissioner Scoot Gottlieb made reference to this point which you can read in the following link: (https://www.fiercebiotech.com/biotech/gottlieb-criticizes-sponsors-continued-reluctance-to-rethink-clinical-trials).

Focusing on how we conduct clinical trials will differentiate one organization from another beyond the science, and perhaps provide that oft sought-after competitive advantage.  Whether you are looking to bring the next CAR-T treatment to market, or the newest gene therapy, or the next Alzheimer’s treatment, once the trials have begun there is very little you can do to influence the success or failure of those experiments scientifically. What you caninfluence is all of the supporting factors that facilitate starting, conducting and completing those trials as quickly as possible, and getting and analyzing the data as expeditiously as possible. Trial results – the culmination of the scientific effort – will make the difference in your clinical, corporate and personal success. Obtaining those results with the appropriate quality and speed are the things you can control, and are worth investing in improving.