Although it can be tricky to acquire proper clinical site training, inadequate planning for a research study’s training needs will create unnecessary, avoidable costs down the road. Let’s take a look at a not-so-uncommon scenario. You budgeted about $20 million dollars to complete your Phase III clinical trial.  You spent months fine-tuning the protocol to perfection.   All of your third-party vendors are engaged and their systems are operational.  Regulatory and ethics approvals are expected any moment and the investigational drug is at the depots ready for distribution. Your investigational compound is meeting an unmet medical need so your clinical sites are especially motivated to start enrolling.  In fact, 100% of the site staff have completed their required online training modules – a first in your organization’s history!  What could possibly go wrong?

We’ve compiled our all-time favorite list of things that can go wrong when it comes to sites actually implementing that perfect-on-paper protocol.  If you can answer yes to all these questions then YOU DON’T NEED US!  You’ve mastered the art and science of effective site training and preparation. Congratulations! But if you can’t answer yes with confidence to even a few of these, you may want to put us on speed dial.  All of these lend themselves to our virtual protocol simulation training approach. We’ll give your protocol a test drive through our dissection and analysis process.  We’re confident that we can find a thing or two that could derail your study.  We’d be delighted to help eliminate those pesky deviations from rearing their ugly heads before it’s too late.   

 

Without calling you in a panic, will your sites know what to do if…

Enrollment

• A potential subject doesn’t have a documented history of one of your I/E criteria?
• The perfect pre-screen-qualified subject takes a prohibited medication the evening before the randomization visit?
• The subject wishes to participate but their personal physician doesn’t want them to?
• The central reader’s image uploading portal goes down while they are submitting a critical source document needed before randomization…and the subject is waiting in the office?
• The site can’t get the centrally provided ECG machine to work?
• The subject tests positive for THC the morning of the randomization visit?
• The central lab results conflict with the local lab results?
• The subject got a late start on the prohibited medication washout period and the screening period is running out?
• The site realizes they enrolled a subject who was not eligible?
• The subject’s source documents reveal conflicting information about a certain eligibility criterion?

Study Drug Prep and Administration

• The study drug arrives out of the required temperature range?
• The study drug appears contaminated when they check it?
• The site finds out at the last minute that the subject can’t swallow pills?
• The subject isn’t tolerating the dose?
• The subject is non-compliance with the dosing regimen?
• The subject forgets to take their medication?
• The subject takes their medication at the wrong time…with or without food (in contravention of the protocol requirements)?
• The site forgets to follow the dose tapering schedule?
• The site realizes the study drug just expired and the subject is due for a refill that day?
• The subject reports that another family member took several doses of the study medication?
• The site inadvertently breaks the blind when administering the study treatment?
• Weight-based dosing is required and the subject’s weight changes during the study?

Visit Schedules

• The subject has to miss a visit due to a family emergency?
• The subject is a no-show for a visit?   
• The subject is a no-show for several visits?

Study Procedures / Equipment

• The required equipment doesn’t work or breaks just prior to the study visit?
• The staff person certified / approved to perform certain tasks is unavailable for a given day?
• The subject is not complying with their ePRO requirements?
• The subject’s wearable device stops working?
• Study supplies don’t arrive in time for a subject’s visit and the visit window is expiring that day?

Safety Management and Reporting

• The subject has an AE of Special Interest?
• The subject received a prohibited medication for an AE that occurred while they were out of the area and the PI couldn’t be contacted?

 

(In case you were counting that’s only 32 and not 150 things that could go wrong, but you get the idea).  Send us or share your trickiest “what if” scenario.  We’ll add it to the list and see if we can’t just find a way to create a good simulation vignette of it!

I have seen in my own life the power of nature vs. nurture.  I was adopted at birth and recently connected with six birth siblings.  It is interesting to observe both the power of nature and nurture.  We were raised in different homes and environments that helped shape who we became as adults.  At the same time, you notice similarities with each sibling that comes from the genetics that we all share.

I think corporate culture is similar.  There is both the nature of the culture that you want to develop while also nurturing its application in your company.

At Pro-ficiency, we determined the nature of the culture and values that we wanted to establish for our company.  The below chart is an expression of our cultural aspirations.

Our team is a mix of artists, scientists and business experts.  We intentionally constructed the DNA of our values to be as unique as the team that we have assembled.  We wanted to avoid traditional corporate jargon.  We settled on four core elements of our values:

• Pioneer
• Solidarity
• Spirit of Service
• Relentless

Surrounding those values is a 360 circle of trust among team members.

We are pioneers.  This reflects both the spirit of our founder Dave Hadden and the uniqueness of our solution.  As we grow our business, we will look for expansion opportunities by seeing both the problem that we are solving and our solution in a unique way.  There are several Albert Einstein quotes that we love at Pro-ficiency that captures our spirit as Pioneers:

• “A person who never made a mistake never tried anything new.”
• “No problem can be solved from the same level of consciousness that created it.”
• And his best quote… “learning is an experience, everything else is just information.”

Secondly, we value Solidarity.  Our success comes as a team, not as an individual.  We value diverse thought while focusing on the same outcome for our customers.  We move and operate as a team guided by True North for our business and our “OKR Management System” as our organizing framework.  We share a common goal with our customers of improving the operation of clinical trials.

Third, we operate in a Spirit of Service.  We want to better enable our customers to accelerate drug discovery.  This is personal for each of us as we have family members that have been impacted by miracle therapeutics developed by the industry that we serve.  There is no higher calling than helping improve human health and quality of life.

Our Spirit of Service also extends to the communities that we live in.  We encourage our team members to share their unique talents and resources in their local area.  Last week we had our first community service event Filling the Bus with school supplies for students in the Durham County school district near our office.

Finally, we are relentless.  We are driven by being the best at what we do.  We aspire to delight our customers in the design, delivery and support of our simulations that transform protocol delivery.  We value having high-performing, execution-driven team members.

With those four attributes of the “Nature” of our culture, how do we “Nurture” them?  

First of all, it starts with the individuals that we bring onto the team.  We interview carefully for these values.  We also make these values inherent to the performance review process for each team member.

Secondly, we review our core values in each monthly All Hands Meeting.  We want these values to be more than a slogan hung on a wall.  

Third, we embed these values into how we operate.  As we built out our company growth playbook, we focused on new pioneering innovations rather than “me too” technologies.  Our “OKR Management System” is also an example of how we restlessly measure our execution against the key performance indicators for our business.

Finally, we live out every day in the Spirit of Service to our industry and our community by providing exceptional products and services.

Ultimately, the most valuable asset in our company is our people.  The culture is simply an expression of the values that guide our journey to True North.

Jim Collins is one of my favorite teachers of what makes great companies tick.  He has authored amazing books like Good to Great, Built to Last and How the Mighty Fall based upon his 25 years of research.  Here is a quote from Jim on developing a great culture.

Disciplined people who engage in disciplined thought and who take disciplined action—operating with freedom within a framework of responsibilities—this is the cornerstone of a culture that creates greatness. In a culture of discipline, people do not have jobs; they have responsibilities. When you blend a culture of discipline with an ethic of entrepreneurship, you get a magical alchemy resulting in superior performance.

We believe that we have settled on the perfect cultural framework for our team.  Experience the Pro-ficiency culture by having us partner in the delivery of your next clinical trial.

Are Your Sites Failing Your Training?  If Not, They Should Be! 

Did you know that 100% of a seasoned clinical research audience attending a recent webinar all agreed on the key metric that should define investigative site training success?  Can you guess what that was?

It had nothing to do with timely completion of training, accuracy on protocol knowledge checks, or site satisfaction of the training approach.  Instead, there was unanimous agreement that site training success should be defined as zero defects.  More specifically zero IMPORTANT protocol deviations.  That’s a lofty goal for sure, especially since we know that too many of these IMPORTANT protocol deviations can sink your trial.  But we are convinced that the goal of zero important deviations is absolutely achievable with the right training strategy and methodology.   Certainly, this assumes a reasonable study design but barring insurmountable protocol-related issues, there is really no reason why studies should suffer from “deviation-itis.”  

As an industry, we’re getting better at identifying and tracking deviations in real-time.  Catching and mitigating deviations early on are one weapon in our arsenal for combatting deviations but the damage is already done by the time the deviation has occurred.  The subject and/or data integrity may have already been put at risk.  It’s like trying to put the toothpaste back in the tube.  You may be able to salvage what’s left but you’ve already wasted that resource (granted, toothpaste isn’t as precious an asset as a clinical trial subject, but you get the point).

The other limitation with linking zero defects to training success is that it’s a lagging indicator.  Not that it shouldn’t be a key metric, but it doesn’t allow the sponsor or CRO to identify which sites / site staff are most and least likely to deviate, and in which areas the deviations are most likely to occur.  

Enter protocol simulation training.  By simulating the most realistic scenarios that sites will face in the study, you can actually measure how they will perform.  Will they make the right decision on:

• What to do if the subject takes a restricted medication just before the randomization visit?
• How to address a temperature excursion of the investigational product?
• Whether an AE is reportable as an SAE or event of special interest?
• What should be done if the subject misses a dose or study visit where a procedure can’t be completed?

Identifying and taking action on any potential deviation such as these is one thing, but ideally the training allows the learner to critically think through preventive actions.  The simulation scenarios should not only model what can go wrong and assess potential corrective actions, but more importantly, how the issues can be prevented.

Simulation allows the site staff to practice the protocol in a safe environment before exposing real subjects and real data to potential risks.  There is a well-known adage that real learning takes place when you make a mistake.  So we actually want our sites to fail in the training.  In fact, failing fast and failing often in the simulation accelerates their protocol learning curve.  Conversely, the more the sites know the material, the quicker they can get through the training and have their competency for making the correct decisions reinforced.

Simulation can be done in live Investigator Meeting Workshops, during Site Initiation Visits and through eLearning. Simulated eLearning however provides a number of advantages.  One can measure the number of times it takes the learner to get to the correct information.  These analytics provide a leading indicator of the site’s performance in the trial.  It also creates an opportunity to provide feedback and mentoring in a consistent manner if the learner makes a mistake.

Here’s to allowing sites to FAIL in the simulated trial so they can SUCCEED in the real one!

They all started in a garage.  

Our founder Dave Hadden is a serial entrepreneur.  He has founded several successful companies in his career with Pro-ficiency being his most successful to date.  After building the foundational software technology for creating simulations, Dave needed a studio to shoot the video elements of simulations.  His garage was the perfect location for setting up the first Pro-ficiency studio.

By the end of 2020, there were more than 800K businesses in the US that were less than one year old.   The data further shows that the largest number of new startups likely took place during the COVID year of 2021.

A study conducted by IBM Institute for Business Value (IBV) and Oxford Economics found that 90% of start-ups fail within the first five years due to the lack of innovation and unique business models.  Dave has a track record of developing companies that uniquely solve problems in the healthcare segment.

According to Artem Minaev, 7.1% of the startups in the world operate in the Fintech industry. Followed by Life sciences and healthcare with 6.8%, Artificial intelligence with 5.0%, Gaming 4.7%, Adtech 3.3%, and Edtech with 2.8%. Even though there isn’t completely accurate data about industry distribution, it’s clear that modern startups gravitate towards the internet and digital technologies.

Dave’s selection of healthcare and life sciences was not by accident.  He had seen the challenges first hand with inadequate, outdated approaches to preparing clinical trial investigative teams for their critical role in drug discovery.  These didactic training approaches had changed little since the days of Socrates and led to protocol deviations and systemic delays. Dave’s vision was to create an immersive training experience that improved the execution of clinical trials.  

Fatimah Lateef, from Singapore General Hospital, has proven that simulation is the most effective way to develop health professionals’ knowledge, skills, and attitudes, while protecting patients from unnecessary risks.  He also points out in his article, Simulation-based learning: Just like the real thing, that healthcare should embrace simulation training tools just like the fields of aviation and military.

How has the Pro-ficiency simulation training approach worked in the real world?  The ultimate measure of success is whether the training assisted the site staff in avoiding protocol deviations.  Over 87% agreed or strongly agreed with that statement in a recent survey conducted with almost 1,500 investigators that leveraged the Pro-ficiency simulation training platform for a clinical trial.

Pro-ficiency has come a long way since that first simulation video shot in Dave’s garage.  We recently opened our own full-time studio in Research Triangle Park managed by Bobby Natassi, our Emmy award-winning producer.  We also now serve the simulation training needs of over 65K investigators around the world.

Much like HP, Microsoft, Google and Amazon we desire to make a meaningful, global impact.  Join Pro-ficiency in helping accelerate drug discovery by eliminating protocol deviations.

Decisions, Decisions….

 

Yale Medicine posted the following article on July 15th.

Delta is the name for the B.1.617.2. variant, a SARS-CoV-2 mutation that originally surfaced in India. The first Delta case was identified in December 2020, and the strain spread rapidly, soon becoming the dominant strain of the virus in both India and then Great Britain. Toward the end of June, Delta had already made up more than 20% of cases in the U.S., according to Centers for Disease Control and Prevention (CDC) estimates. That number is rising swiftly, prompting predictions that the strain will soon become the dominant variant here.

Just when travel internationally was starting to open up, the Delta variant has paused some of those efforts.  The Delta variant also appears to also affect individuals that have been vaccinated.  The challenge for sponsors now is how to best launch training for a new trial in this uncertain environment.

Many investigators believe that the Pro-ficiency is a superior alternative to in-person investigators meetings.  It is not surprising that they prefer the Pro-ficiency simulation approach over being trapped in on-line Zoom sessions or other eLearning platforms.  The following results, however, are a higher bar.  It appears that investigators are not longing to return to in-person training in a hotel ballroom.

With almost 90% neutral to positive, imagine providing a better training experience without the cost and uncertainty of clinicians traveling into an investigator meeting.  

The ultimate measure of success is whether the training assisted the site staff in avoiding protocol deviations.  Over 87% agreed or strongly agreed with that statement.  

 

In summary, there are many advantages to the Pro-ficiency approach illustrated in this data:

• Investigators prefer the simulation training approach over all other methods
• Simulation training is an efficacious and efficient means of educating site staff

Let Pro-ficiency keep your study launch on track in these uncertain times with our simulation training platform!