The source data verification of clinical trial data is approach to linking quality of data and for being harmless side of regulatory. However, the regulations do not define the limit of Source data verification. This flexibility gives a chance to introduce innovation and application of various methods, targeted and remote monitoring, adaptive monitoring schedules and real time reporting. The remote site monitoring is one of these innovative methods to ensure the quality of data which can save time and cost, which can be utilize on more productive activities such as R&D, implement new technology etc. And most importantly, it increases the work life balance of monitors.
However, remote monitoring involves verification of site documents from remote place. It has challenges as well. The source documents should be certified copies of electronic records, which might not be the case. Hence, remote monitoring cannot be totally replaced with on-site visit which can allow to see how site works. All trial should have delicate balance of remote and on-site monitoring throughout the study.
In this article, we will discuss potential opportunities and challenges of remote site monitoring along with potential solutions to overcome challenges. I am utilizing “Remote Monitoring” term to means a remote evaluation of clinical data at a location other than investigational site.
The Monitoring has been always a considered a vital activity in order to conduct clinical trial and to ensure quality of data and procedures followed for particular protocol. First, I would like to mention about what remote monitoring us NOT. Very often, remote monitoring is confused with Risk-Based Monitoring, Remote monitoring allows monitoring activities which are previously conducted on-site, increase efficiency and speeding up time to market. CRA plays very crucial role, but without spending time onsite or travelling. Instead the CRA performs all the study monitoring processes remotely, using a secure online platform.
“The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).” Section 5.18.3 of Guideline E6 states: “The sponsor should ensure that trials are adequately monitored. The sponsor should determine the appropriate extent and nature of monitoring. The determination of the extent and nature of monitoring should be based on considerations
such as the objective, purpose, design, complexity, blinding, size and endpoints of the trial. In general there is a need for on-site monitoring, before, during, and after the trial; however, in exceptional circumstances, the sponsor may determine that central monitoring in conjunction with procedures such as investigators′ training and meetings, and extensive written guidance can assure appropriate conduct of the trial in accordance with GCP. Statistically controlled sampling may be an acceptable method for selecting the data to be verified.” So, the next question is why industry still wants to focus on site monitoring for 100% source data verification for most of trials?
It has been always believed that more source data verification assures better quality data. Especially when regulatory does not define how much source data should be verified, sponsor and monitors are on the side of caution. In fact, FDA recommends a review of a “representative” number of subject records and not all records . In August 2011, Monitoring Guidance Document (1988) is replaced to adopt Risk-Based Approach to Monitoring (Draft) [3,4]. To removing the stigma that 100% source data verification is the only way to product approval, FDA is encouraging sponsors to take credit for activities that are conducted throughout the study that contribute to the
responsibility of monitoring.
Remote monitoring has been challenging to date because
of the accessible infrastructure compliant to HIPAA and 21 CFR
Part 11 which allows access to patient data, trial master file and
Remote monitoring concept is future of clinical research, and
we are not fully convinced to adopt this concept. We must make
several practical consideration about therapeutic area phase
and complexity of trial etc., and clearly this carries the risk of
missing critical issues. Technological considerations related
to data, hardware, and connectivity as well as expertise in
implementing and integrating remote clinical trial components
are also essential for the success of this concept. Although
it may be expected to have remote monitoring method cost
effective, initial implementation will likely be more expensive
than traditional approach. Because, it required require parallel
processes in place. The air of resistance toward this concept
from clinical research teams and clinical research sites must be
met with a gradual culture change to propel clinical trial conduct
in the next wave of innovation and better serve the patient of the
future. The digitization of clinical research through the remote
trial concept is an essential step in that trend.
Instead of making frequent periodic on-site monitoring
visit, it can be performed at flexible interval based on each site’s
performance and risk level as the study progresses. Sites deemed
low-risk less often and Sites deemed high-risk would be visited
more often. Although the remote monitoring may reduce shortterm
costs may prove to have long term consequences. Hence,
remote or on-site monitoring is not to mutually exclusive, but
should be combined with overall review process and excellent
communication throughout will result in high quality data and
securing compliance. In turn, balanced combination approach
can give confidence that that patients enrolled in their trials
have been protected, their data is accurate.
Amazingly, some sponsors and sponsor representatives are
still embracing the On-Site monitoring process and focusing on
what could go wrong rather than the positives and understanding
the intent of the FDA Guidance. I am hopeful that we will all take
that critical step forward and embrace the change that is on our