The Digital Paradox: Research Sites and the Clinical Trial Protocol

The research shows that investigative site staff reference the protocol online via a desktop computer, through hard copies, and by asking study monitors. The process by which site staff find information from the protocol is electronic, but it lacks the accessibility, convenience and immediacy typically associated with digital.

There are a few contradictions. For example, while the protocol may be electronic, it is most often referenced via a desktop computer in a fixed location. Questions are commonly answered by scrolling through the index to find a page number or by asking someone else. And while the most commonly accessed sections of the protocol are eligibility criteria and schedule of visits, the protocol doesn’t tend to be stored where patients are seen.

The conduct of clinical trials is guided by “electronic paper”

Research staff are interacting with the protocol more as “electronic paper” than as a digital resource. This is illustrated first by the fact that the protocol is most often referred to on a desktop computer. Very rarely are respondents using mobile devices, such as tablets or smartphones. Considering that most are scrolling through an index to find a page number, it is not surprising that they aren’t accessing the protocol via devices with smaller screens. Even the modes of search are manual – looking up a page number, scrolling through perhaps dozens of instances of a keyword search, or asking someone else.

In some ways, a desktop computer is perhaps even less convenient than paper in that it is in a fixed location. While staff may think they are “digital” because they are referring to an online version of the protocol, truly digital would be untethered access with instant, contextually aware answers to precise questions rather than broad brush category references. It’s the difference between finding the page number for the schedule of assessments section and getting answers on what specific procedures must be performed during Visit 3.

There is a degree of separation between the protocol and the patient

The protocol is treated more like a static reference, rather than a real-time resource to guide the conduct of clinical trials. Patients’ lives have adapted to include the investigational products of clinical trials, they’re living with – and possibly because of – these treatments. AEs don’t know office hours, they can impact patients at any time, which therefore necessitates that research staff have immediate access to quickly and correctly make decisions.

There are inefficiencies and time lost in providing answers for research staff when they are engaged with a patient. Typically, physicians won’t have more than a few minutes with a patient to determine if he or she is eligible, and for which clinical trial. If information is not readily accessible, this can lead to challenges with enrollment, which we already know is a problem for many sites.

Study design complexity presents challenges for staff to find answers in the protocol

The way research staff find answers in the protocol is time consuming and manual. Managing toxicity and adverse events are typically guided not only by sponsor SOPs but also other regulatory and safety reporting guidelines. As a result, these sections of the protocol could have potentially confusing or contradictory instructions when considered against these other sources.

Medical monitors are not frequently a direct source of information for sites. With the CRA often as the intermediary between sites and medical monitors, this delays answers and also limits the visibility of medical monitors into the trial performance.

It's time to redefine the digital protocol. Here's why.

Benefits for Investigative Research Staff

Electronic and digital aren’t the same thing. So, what does it mean when the protocol is digital? We believe that answers are available in seconds, contextually aware, and present with the patient.

Answers in Seconds

In the digital world, you ask a question and you get an answer. Under the covers, the search engine is analyzing all of the available information to generate the most relevant results – in seconds.

In clinical trials, there are multiple questions. And answers may come from a variety of documents beyond the protocol, including investigator brochures, lab manuals, CTCAE, etc.

What if any research staff could type a question into a search bar from any digital device and the results are returned in seconds after analyzing all available documents? The focus then shifts to the best answer instead of what section of a document. It reduces the burden on the user because the best answer is found among all of the documents. And it also eliminates any worries about document version because answers are only returned from the approved, current protocol for that site.

Contextually-Aware Answers

Let’s take the example of “hypertension.” It may be part of the eligibility and so it may appear in either the inclusion or exclusion criteria of the protocol. But if during the trial a patient develops hypertension, the word could also appear in the toxicity management section of the protocol.

A simple scroll through the index of a PDF directs the user to a list of topics but doesn’t necessarily answer the specific question. Similarly, doing a keyword search in a PDF would return multiple hits to the keyword, which then puts the onus on the user to look at the context of each instance of the word.

What if a physician could just type in eligibility 140/90 – and get an answer whether the person is eligible for a clinical trial? Or dose 160/95 to understand whether to modify dosage based on the current blood pressure levels? Physicians and nurses can spend less time and be more precise to find answers in the context of their questions.

Present with the Patient

Time with patients is limited. Decisions need to be made quickly and in compliance with the protocol.  Whether the patient is eligible for a given clinical trial, what conmeds are permitted, and which procedures should be performed for a given visit, investigators and research staff need to make decisions from the latest study information.

From any smartphone or digital device, answers from the protocol are always where the patient is. This means physicians and nurses can focus on patient care. For example, protocols may be amended to update enrollment criteria. Therefore, it is critical investigators and research staff have the latest study information when they are with patients to enroll the right study participants and reduce errors. Gone is the need to walk to another room to log into a computer or flip through paper.

What’s in It for Sponsors and Monitors

If sponsors and monitors aren’t asking how research sites are interacting with the protocol, they should.

First, it is a measure of how engaged sites are with the trial. Actively looking at eligibility criteria, for example, is a good indication of whether sites are trying to recruit for the study. It also speeds enrollment of the right patients because research staff are confirming the criteria on the spot. Second, conducting trials strictly by the protocol reduces errors, minimizes deviations and protects patient safety.

Sponsors and monitors have a role to play in helping to alleviate the burdens on research staff in conducting trials. And they both have something to gain with better visibility and earlier insights into trial performance.

Better Visibility

It may sound obvious, but paper protocols don’t give sponsors or monitors any idea who is looking at the protocol or what answers they are trying to find. Similarly, “electronic paper” documents don’t offer much more insight.

Usage trends of portals are nice to have stats – if you can get them in the first place. And unless you are regularly running a report, they offer a picture that is after the fact. And usage still doesn’t answer the question of what the person was really looking to answer.

When the protocol is truly digital, sponsors and monitors can see in real time who is looking at the protocol, how often and what they are trying to find. In fact, remote monitoring necessitates this digital insight.

CRAs can target precise support for sites who aren’t meeting their enrollment targets. Site queries can also be handled faster. And central monitors can compare usage trends across sites to evaluate key indicators, such as enrollment or protocol deviations.

Early Insights

With real-time insights, sponsors and monitors can proactively address risk factors. High profile search terms may indicate safety issues, while high frequency search terms could highlight where further clarification is needed.

Let’s take the example of toxicity management. If there are known symptoms that could be an early indicator of a known side effect, alerts when sites are searching for this would allow sponsors to react more quickly to guide the investigator on specific actions.

Similarly, if there are consistent questions in the same area, such as permitted conmeds or certain eligibility criteria, sponsors could provide clarifications to monitors and site staff so that everyone has consistent, real-time guidance.

Sponsors have a window to see into the trial performance. By connecting sponsors with the staff conducting the trial, they have a better understanding of performance and can proactively offer guidance or additional support for items blocking sites and trial success

Where Do We Go from Here?

At the end of the day, it’s about making it simpler for research staff to safely conduct clinical trials so that life altering treatments can safely come to market faster.

We see that research sites are stuck in a bit of a time warp. Physical paper is still a dominant source of information. Even when the protocol is referenced “electronically,” it is used more like paper on a desktop than a digital resource. There is still a reliance on CRAs as an information source, which delays responses to questions.

If you think about the patterns in your own life, how much of it is digital and mobile? Physicians, nurses and CRAs aren’t any different. And as we have more “digital native” staff, it is unlikely that they will be satisfied with antiquated practices.

With COVID-19, paper itself poses risks of contamination. And with more remote monitoring, clinical trials must move to be more digital.

Speed and quality of answers are critical to any clinical trial. In a digital world, answers for research staff are just a couple of clicks away – anytime, anywhere. Every answer provided itself tells a bigger story for sponsors and monitors to evaluate trial performance and proactively address issues.