Unfortunately, sites are used to many frustrating things in clinical trials. As more frustrations feed the irritation fire, it gets to a point when sites would just rather focus on something else.
To speak in clinical trial results language – picture a graph where along one axis we have irritations, and the other axis is time. As irritants increase over time, they compound and get to the point where the site has had enough and it’s not worth it anymore.
It’s a little like how a forest fire might start – there’s a spark or two that lands on something combustible and then it sits there and smoulders. It may take minutes or hours, but unless it is addressed and put out, it can turn into a raging fire that consumes everything around it.
The irritation effect often begins before a study starts. The most frequent trigger I hear about for sites is currently with Investigator and staff training. Frequently, the training is too long, redundant, inefficient, unproductive, and plagued with a host of technical problems: trouble logging in, links that don’t work, or problems receiving completion certificates. Sites are never compensated adequately for the training they are asked to do.
Other pre-study irritants include not receiving all the information needed in enough time prior to study start; constant revisions to reg docs; CRAs who don’t have the information to answer questions at prestudy and initiation visits; and budgets that are far too low for the work involved.
Most often, study materials (i.e. lab manual) arrive last minute and then begins the pressure to start seeing study candidates when the site hasn’t had the time to review or organize everything.
The next wave of irritations occur as the study is starting. Additional requirements come to light that weren’t in the protocol or prestudy information. Regularly, there are delays in receiving study supplies.
Some CROs convince Sponsors that more frequent check-ins with the study coordinator will be the thing that improves site engagement and motivation. I can tell you from 27 years of experience that this approach typically has the opposite effect. Requiring the weekly check-ins and copies of the pre-screening logs only serves to further frustrate the site and the check-ins cause the site to checkout. CRA check-ins are a delicate dance. There are some CRAs that approach the site with an attitude of partnership and understanding. The Partnership approach views the site as a true partner (and not a subordinate that needs to be told what to do) and has a goal to help the site reach their potential on the study. The Understanding comes in when the CRA appreciates how busy the coordinator is and how hard they are working. Those CRAs are worth their weight in gold and their check-ins are welcomed.
Poorly designed site documents or tools create more work than they save. Examples of this include 50+ page consent forms, Lab Manuals, or other study materials with errors or incomplete information. Protocols with inconsistencies or unclear information further exacerbate the frustrations. Difficultly getting responses from the CRO or sponsor cause temperatures to rise.
Oh, yeah – I almost forgot – the revolving door of the constantly changing CRA. The amount of extra work that this adds for the site continues to grow. It often results in repetition of work that has already completed, new tasks for the coordinator and delays in key items. Usually, the thing that gets sacrificed is drug reconciliation. Shelves of returned drug waiting to be, well,… returned. All these things lead to more expense for the site with no compensation. We need to start seeing fees in study budgets to compensate the site when the CRA changes.
Next topic of irritations – cash flow of the site. Let’s talk payments. Or rather, the lack thereof. Here’s the short version – rarely, rarely, are site payments made on time in accordance with the contract. Can you imagine if the site failed to follow the terms of the contract? But when the payment isn’t made on time – what happens? Well, for starters, the site dips into their line of credit to pay the bills. It’s no wonder that Sponsors and CROs who pay monthly and on time get rated higher by investigators. If all things are equal and two studies are going well and one pays monthly and the other, pays quarterly or is late by six months or more – which study do you think gets the attention?
In most clinical trials, there will be things that come up that don’t go smoothly. That’s just what happens in clinical research. The degree of impact and how they are handled determine how serious the irritation becomes.
When this happens, the 5 Cs come into play: Critical, Clear, Concise, Commitment Communication is the key to keeping the site engaged in the study. The site needs to believe that as a sponsor and CRO, you are taking the situation seriously and doing everything possible to resolve it. Far too often, sites experience long delays in getting issues addressed. Take for example, the case of the malfunctioning eCOA or ePRO. This happens with alarming frequency in clinical trials. A backup plan must be in place before the study starts, and when issues arise, it must be addressed with the vendor expeditiously. It’s immediately critical if the issue affects the conduct of the participant visit. All too often, sites are told that the vendor is “working on it” and that can drag on for weeks or months. In an era of “patient centricity”, anything that affects the proper, efficient conduct of the participant visit is an immediate, significant motivation and momentum killer.
Applying the 5 “C”s”
When an issue arises, it is Critical that it is escalated, dealt with swiftly, and an initial response informs the site immediately that the notification of the issue was received and was escalated. The initial response must be followed by a detailed plan for resolution. The plan should be Clear and Concise on the plan to resolve the situation. Don’t forget to include the Commitment Communication.
Notice that “Commitment Communication” is actually one item. It’s not Commitment and Communication. They are one action. Def: “Commitment Communication” – a form of communication that expresses one’s commitment to fix the problem the site is experiencing and details the steps being taken.
Please don’t leave sites in the dark when issues arise. It causes the site to lose confidence in the study leadership and will negatively affect Investigator and site motivation.
Clinical Research 