Completeness is an essential component of TMF health. A TMF’s purpose is to tell the story of a clinical trial. An incomplete TMF is like a book with missing pages—even if the story is well written, it is inaccessible to any reader. In a few previous blog posts we’ve discussed how an incompleteness crisis can be prevented from the very first moments of a trial: by incentivizing TMF health, by defining and communicating TMF objectives, and by recognizing that no CRO or third party can truly take on all the responsibility for your TMF. Sometimes, however, a clinical trial does not go to plan. More often than ever, sponsors are discovering upon closeout that their TMF is woefully incomplete.
It’s essential to adopt an incremental approach in response to a TMF completeness crisis. After reestablishing a dialogue with TMF stakeholders and regaining visibility of the TMF, a list of action items and/or missing documents can be developed. Closing out this list of action items is not a simple task. Beyond the number of action items (which could number into the thousands), site level documents will likely need to be recovered. Reflecting on the most common completeness crisis scenario, where a sponsor discovers the TMF is incomplete at, or even after trial close-out, sites may have received their own close-out monitoring visit, moved on to new protocols, or even archived documents off-site. Trial sites, already inundated with correspondence from sponsors, may not react positively to TMF queries, and may even avoid or ignore document recovery attempts. So how can our completeness action item list be closed? LMK’s top four principles for TMF site-contact respects the limited resources of trial sites and ensures document recovery does not come at the expense of the site-sponsor relationship.
Identify your contact
Despite the growth of multi-center and international clinical trials, maintaining a healthy working relationship with each trial site remains a critical component of the success of the clinical trial and TMF. The first step in building a healthy relationship with a trial site is to know the name and role of the person you are calling. Certainly, when trying to close out a long list of TMF action items, there will be temptation to skip the niceties and simply cold-call for a document. However, emailing a shared inbox, calling to speak with a staff member who no longer works at the site, or asking for a document from an anonymous voice on the other end of the line is not likely to successfully close an action item.
Consider who else may be contacting the site
Clinical trial sites and their clinical research coordinators are flooded with emails and phone calls every single day. Your protocol represents only one concern among many. Multiple contacts for the same issue results in contact fatigue and can cause a trial site to avoid any contact with your team altogether. Many modern CTMS systems allow a log of site contact to be created. Sadly, due to the administrative overload of clinical operations professionals, the site contact log feature may not be used. Still, your team should consider employing this feature when resolving TMF queries: nothing frustrates a clinical trial site more than receiving the same request for a document that they have already received or resolved with another member of your team. Respect a site’s time and resources by reducing the instances of contact as much as possible and you’ll find site staff will be much more willing to support your goal of TMF health.
Learn the whole story
Just as the TMF tells the story of a trial, a missing document usually has its own story to tell. Solving the underlying cause of a site’s incompleteness might be necessary to truly resolve outstanding TMF action items. For example, did the site experience a PI change or other staff change? Did the site have many different monitors, enrollment trouble, or a long period of inactivity? Might the site’s TMF incompleteness be the product of a specific event or overall unhappiness with the protocol or methods of the sponsor or CRO? Each clinical trial site has unique needs and challenges—and these needs and challenges should be understood before picking up the phone or sending an email to request a document.
Don’t just check a box
Have you been tasked to collect a TMF document and felt like you were assigned a fool’s errand? Too often, TMF SOPs specify incompleteness due diligence activities or a number of contact attempts that result in frustration for all parties, both at the CRO or sponsor and at the trial site. The above suggestion implores TMF professionals to take the time to understand a site before initiating a document collection step. If the story of a site already contains multiple failed attempts and a deteriorating or combative relationship, then perhaps ‘going through the motions’ is not in the best interest of anyone involved. As we’ve discussed, a TMF completeness issue often signifies other compliance or performance issues. If contacting the site feels futile it’s time to have a deeper conversation with the entire clinical operations team about what went wrong, and how such mistakes can be prevented in the future.
Although a common occurrence, contacting sites for a missing TMF documents may suggest poor TMF health and may cause a Regulators to suspect more serious forms of non-compliance. When the TMF is incomplete and site contact is required, it’s important to realize that all TMF-related site contact has the potential to strain the sponsor/CRO and site relationship, document collection is time consuming, and site contact does not often result in the missing document being successfully collected. Site contact for missing documents, therefore, should be carefully considered and limited in scope. Careless and excessive site contact can potentially deepen, rather than mitigate a completeness crisis.