Homeostasis and medical device clinical trials

Danny talks about how to strike a good balance between people and technology for monitoring medical device clinical trials.

Are real-time alerts too much of a good thing for monitoring your study? Maybe real-time alerts for patient compliance in medtech studies is just a fad – a fad just like WhatsApp.

I had a conversation with my friend John who has worked for years in digital technologies in the public education space. With over a billion people on social media, John was concerned that the human element is getting trashed.

My answer to him was – “No way”. People, both individually and collectively after they go through a change (especially a big technology change) they tend to return to a state of homeostasis.

The homeostasis of information

Stop for a moment and consider how much of your data sharing and private messaging interaction is digital and how much is paper and then ask yourself why clinical trial compliance monitoring is still dependent upon paper interactions.

If you are a CRA, then you have responsibility for ensuring compliance with ICH GCP regulations, timely reporting and compliance of the trial to the study protocol and timely reporting of adverse and severe adverse events.

– Reflect on what’s happening to email as more and more of your activity is via your phone.
– Reflect on children who do very little on email and almost everything in WhatsApp and Instagram.

It is May 2018 and a large proportion of our interactions with friends (and colleagues and increasingly customers) are in real-time over WhatsApp – and fewer and fewer of your interactions are via email.

With the shift to a mobile-first culture – and as the younger users become the adults – the importance of messaging apps will only increase.

Then reflect on your own personal ups and downs – the times in your life when are more social or less social – when you are more wired or less wired, when you need to be with yourself and write code or when you need to be with friends and drink beer.

Homeostasis (from Greek: ὅμοιος, “hómoios”, “similar”, and στάσις, stásis, “standing still”) is the property of a system that regulates its internal environment and tends to maintain a stable, relatively constant condition of properties such as temperature or pH. It can be either an open or closed system. In simple terms, it is a process in which the body’s internal environment is kept stable. It was defined by Claude Bernard and later by Walter Bradford Cannon in 1926.

I said – “Look, people have small numbers of really good friends in real life and online.” The statistics of Facebook statistics official website shows that the average number of Facebook active users’ friends was 130, and an analysis of a dataset of Twitter conversations collected across six months involving 1.7 million individuals found that users kept stable relationships with 100–200 users. The “economy of attention” is limited in the online world by cognitive and biological constraints as predicted by Dunbar’s theory.

Even if a person has a huge social graph of 15,000 friends – she will still need the physical connection with a friend over coffee for important decisions and challenges.

Even as we develop friendlier and faster cloud applications and more usable and faster mobile apps, online interactions will never replace the physical connection. I believe that the need for physical connection is not age-dependent (teenagers exchange hundreds of WhatsApp messages a day) but for important transactions (like closing a contract), we need direct interactions.

As if providing my point, this morning, a neighbor runs into me on the street. Sarah didn’t send me a WhatsApp or a FB private message or update her status (even though we are friends on FB). It was an epiphany moment when you learn something important and just have to share. She has a great physician-patient relationship with her GP and just had to share some important guidance she received from her family doctor.

“How many people do you know who say they don’t want to drink anything before going to bed because they’ll have to get up during the night!?”

I replied – “I imagine all the guys over 50 and that’s a bunch of people”.

She says – let me share guidance I received from my family physician this morning (it’s 40 centigrade today in Israel and really hot; the topic of drinking water always seems to comes up).

Gravity holds water in the lower part of your body when you are upright (legs swell). When you lie down and the lower body (legs and etc) seeks level with the kidneys, it is then that the kidneys remove the water because it is easier. I knew you need your minimum water to help flush the toxins out of your body, but this was news to me. Her doctor used the word homeostasis – which I remembered from high school biology

The correct time to drink water is actually very important – drinking water at a certain time maximizes its effectiveness on the body:

– 2 glasses of water after waking up – helps activate internal organs.

– 1 glass of water 30 minutes before a meal – helps digestion.

– 1 glass of water before taking a shower – helps lower blood pressure. 1 glass of water before going to bed – avoids stroke or heart attack.

Her physician added that water at bed time will also help prevent night time leg cramps. Our leg muscles are seeking hydration when they cramp and wake you up with pain in your legs and knees.

In the body, most homeostatic regulation is controlled by the release of hormones into the bloodstream. The kidneys are used to remove excess water and ions from the blood. These are then expelled as urine. The kidneys perform a vital role in homeostatic regulation in mammals, removing excess water, salt, and urea from the blood.

So what does homeostasis have to do with clinical trial monitoring of compliance to the protocol?

Everything.

Just as homeostasis in the body ensures that internal body environment is kept stable, monitoring is a process in which the internal environment of the clinical research is kept stable.

In medical device clinical trials monitoring of patient and PI compliance with the protocol required. Timely data collection is crucial to measuring and assuring a rate of patient recruitment that will sustain the statistical power for the study. Clinical trial monitoring means being in close touch with patients – especially in medtech studies, where patients are using the device in a near-real-life experience and they may (they will) do unexpected things – taking the treatment on non-treatment days or forgetting to report 24 hour follow-ups in the ePRO system.

The traditional method of SDV – source document verification basically involves the site monitor comparing source documents with the data recorded in the EDC. This is an extremely expensive and wasteful process which results in less than 3% of the EDC records being updated according to a study performed by Medidata. Our own research shows that less than 1% of the data points in a medtech study are updated due to SDV.

Site monitoring costs eat up 30 percent of medical device clinical trial budgets;1 of that, more than half is spent on source document verification (SDV). Why waste precious time and resources checking all data if you only want to verify critical data? (Risk-based monitoring in the clinical cloud)

The reason for this is that clinical data collection in sites is slow and easy
to verify. The CRF forms are validated with online edit checks at source – and
as a result, there is little added-value to be gained from a manual comparison
between a paper form and a digital record.

In medtech studies, where the data is collected digitally in real-time, SDV does
not even have a role to play at all.

More crucially – SDV and onsite visits totally overlook the human element.

In a sense, if you are a CRA – it is easier to stay in a comfort zone of faxes,
paper and filing and and submitting site visit reports than to use online
real-time alerts of non-compliance. We see this all the time with the early-adopter customers
who use our compliance as a service product.

The business process disconnect between study monitors and sponsors

While a sponsor of a medtech study understands  the crucial importance of patient compliance to the study protocol in terms of time, money and statistical significance; a study monitor  focuses on executing a process unrelated to time to market of the medtech product.

However, digital tools can improve processes.

Online alerts and trends are a great way for a smart CRA to save time and improve GCP compliance
with less work and focus attention on higher-risk GCP issues. Site visits become more productive,
since they are not devoted to processing paper by improving processes.

In our social interactions – most homeostatic regulation is controlled by
sharing and private messaging, online and offline. When you need it a personal interaction – you have
a 1:1 meeting and when not, WhatsApp is extremely useful.

Our interactions with patients and research sites is no different. The online digital tools help focus on the real issues and resolve them in real-time.

Mindful interaction with patients and sponsors is best when you get out of your fax-comfort zone.

Whether good news, bad news or just a Happy Birthday – sometimes you just need the personal and physical touch of a real, warm human being and not just a fax.

Danny Lieberman – check me out on LinkedIn

Physicist by training, medical device security expert, serial tech entrepreneur.

Flaskdata.io | The team behind the world’s fastest patient compliance system Helping over 300 sites around the world and thousands of patients/month

Leave a Reply