By Kelly Jasko, Lead Clinical Research Associate
Every year, the U.S. Food and Drug Administration (FDA) releases metrics detailing the outcomes of the Bioresearch Monitoring (BIMO) inspections done at facilities conducting clinical research within the previous year. Of the 104 Sponsor/Monitor/Contract Research Organization (CRO) inspections done in fiscal year 2017, 36 percent were found to have some type of deficiency, resulting in either a Voluntary Action Indicated outcome or an Official Action Indicated outcome.
These outcomes often demonstrate that deficiencies in complying with the regulations were observed. In some cases, the deficiencies may be minor in nature, and in other cases, the deficiencies may be more severe, pointing to data integrity conflicts or even a human subject protection issue. These more severe types of deficiencies are usually evidence of a study that has gone “off the rails” for one reason or another. Maybe you’ve been part of a study team that allowed for study conduct to get out of control, or maybe you’ve “inherited” a study mid-stream that seemed disorganized and chaotic.
Detailed below are seven common causes of a noncompliant study, along with five suggestions for getting your study back on track.
7 Common Causes
- Poorly Written Protocol
Perhaps the biggest, and potentially most frustrating risk that could lead to a poorly run study is a poorly written protocol. Having a poorly written protocol may leave what should be straightforward protocol questions up for interpretation. The protocol is typically the gold standard reference document for study teams, and if everyone is interpreting the same document in different ways, this can lead to inconsistency in the messaging between the study team and with the study sites. Protocols written with this “gray-area” interpretation can cause differences in study conduct among sites and potential loss of data.
- Mismanaged Study Team
Whether the study team on your project is within your company or contracted externally to a CRO, they need to be managed. An inexperienced or ill-equipped study team can have a negative impact on overall study conduct. The monitoring team is the sponsor’s eyes and ears in order to maintain human subject protection and data integrity. Setting clear guidelines on how study teams should conduct potential site assessments, site initiation visits, periodic monitoring visits, close-out visits, and general site management will enable an effective delegation of responsibility and appropriate oversight.
- Inadequate Training
Training is the foundation to clinical trial management. If the study team is not knowledgeable in the protocol, applicable regulations, standard operating procedures, national and international guidelines, the investigational product under study, and any reviewing IRB/EC requirements, then inevitably mistakes will be made, and study mismanagement is likely. An untrained study team will not have the basis in which to adequately face challenges that arise throughout the clinical trial.
- Inadequate Documentation
There is a common adage known to many researchers: “If it’s not documented, it’s not done.” Inadequate documentation will not allow for the traceability required in clinical trials. Unfortunate consequences of poor documentation can include questions from an FDA auditor that you are unable to explain years after their occurrence. This may be most commonly noted in those “inherited,” long-term ongoing clinical studies.
- Lack of Resources
Both appropriate monetary and personnel resourcing are important for the success of a study. Lack of communication, a lag in enrollment and failure to address issues in a timely manner, among other issues, can quickly combine to push the study out of control from a budgetary standpoint. In addition, it is not uncommon for study teams to be consistently pressed for time and working on numerous trials. The research sites may not always have the infrastructure or resources to promote timely data entry or completion of protocol-required follow-up visits. This could lead to issues with obtaining informed consent, delays in enrollment, inadequate data entry, inadequate product accountability, failure to identify adverse events, lapses in IRB/EC approval and more. Each of these could lead to potential data integrity and/or human subject protection issues that, if left unaddressed, could cause issues with the overall study.
- Ineffective Leadership
Strong leadership to motivate a study team toward a common goal is vital to keeping a clinical trial on track. Ineffective leadership can be detrimental to a clinical study and typically starts with inadequate communication and a lack of management of vendors, sites, and CROs. A lack of oversight and leadership to contest the potential lags in enrollment, protocol changes and unexpected issues known to arise in the clinical trial process could cause a wide array of deficiencies within your clinical trial.
- High Turnover
Sponsor, site, and monitor turnover is common within the research field, especially for those clinical trials with long-term follow-up requirements. High turnover can lead to inconsistency in the running of the clinical trial, loss of historical knowledge of how something was handled, and a loss of efficiency from one person to another as the baton is passed.
Overall, the FDA’s common findings following an inspection are the same from year to year and include failure to follow the investigation plan/agreement or regulations, inadequate record keeping, inadequate monitoring and failure to bring investigators into compliance. Identifying the common causes that may impact your study will enable you to better safeguard your study against pitfalls in compliance. However, despite best efforts, once your study is off-track, it’s important to know “what’s next” in study recovery.
Download the complete whitepaper for 5 steps to study recovery.