As a global medical device CRO, IMARC is sometimes asked to “clean up” clinical research sites after things have gone wrong due to poor management or other issues.
Of the 113 sponsor, monitor, and CRO inspections the FDA’s Bioresearch Monitoring (BIMO) Program noted in its fiscal year 2019 report, 27% had some type of deficiency that required either voluntary action or official action.
The most common observations included:
- Failure to select qualified investigators or monitors and ensure the study is conducted according to the protocol
- Failure to maintain adequate records in accordance with 21CFR 312.57; accountability for the investigational product
- Failure to bring non-compliant investigators into compliance
These observations are often a symptom of larger problems our team discovers later, when we begin working with a sponsor or site after they have received a warning letter.
Here are the scariest issues we encounter at clinical sites — and how to avoid them.
7 Scary Issues At Clinical Research Sites
1. 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.
2. 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 for 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.
Enlisting the help of a monitoring CRO gives your trial objective oversight and a consistent approach in this area.
3. Inadequate Training
Training is the foundation of 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, 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.
4. 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.
The acronym ALCOA-C is a good guideline for clinical trial documentation practices. All documentation should be attributable, legible, contemporaneous, original, accurate, and complete.
5. 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. Clinical research coordinators or monitors may not always have the infrastructure or resources to promote timely data entry or completion of required follow-up visits with study participants. 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.
6. 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 at clinical research sites.
7. High Turnover
Sponsor, site, and monitor turnover is common within the research field, especially for those clinical trials with long-term follow-up requirements. The average turnover rate among clinical monitors at contract research organizations (CROs) in the US hit a five-year high of nearly 30% in 2018, an increase from 25% in the previous years, according to a 2020 study by BDO.
High turnover can lead to inconsistency in the management 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.
Avoid These Issues at Your Clinical Research Sites
Hiring an experienced contract research organization from the beginning can help sponsors and clinical research sites prevent serious problems that can lead to delays or violations.
IMARC has more than 20 years of experience helping clinical trial sponsors and sites achieve compliance and earn approval.
Our team becomes an extension of yours. We can assist with clinical planning, protocol development, and risk assessments before your study begins, setting a strong foundation. During your study, we can help you implement risk-based monitoring, train your study team, and assist with data management and safety monitoring.
After your study is complete, we can assist with final audits, data lock and analysis, and conduct a Trial Master File audit to ensure all your documents are in order.