The quality assurance program selected for a research study may be completed either through a monitoring process or an auditing process. Monitoring and auditing are different processes to achieve the common goal of assuring the safety of patients enrolled in clinical trials and the integrity of the research process and data collected. Both methods of quality assurance evaluate compliance with regulatory requirements, IRB functions, informed consent content and process, compliance with study policies and procedures, participant eligibility, control of research drugs and devices, and the accuracy of data submitted [1]. All studies completed under an IND or IDE must undergo monitoring as required by the FDA [2].

The purpose of monitoring is to document the progress of the clinical trial from all aspects, including regulatory, data submission, adherence to study protocol and procedures, and includes a data safety monitoring plan. Monitoring is completed by the study sponsor and requires 100 % verification of study data. This is accomplished through regularly scheduled periodic visits to the sight to oversee the study. Depending on study accrual and the frequency of data collection, these visits may occur as frequently as monthly.

Auditing is an intermittent evaluation of study progress that evaluates a subset of the data collected at a specific time point in the study. Many studies require that 10 % of the patients accrued are audited. It provides a determination of compliance with study policies and procedures, regulatory requirements, and confirms crucial data points through source verification. Audits are generally conducted within the first year of the first patient enrollment and then every 3 years if the site has a successful audit. However, this may be modified at the discretion of the sponsor depending on site performance and accrual.

Guidelines from the FDA state that the IRB review is completed “to assure, both in advance and by periodic review, that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in the research. To accomplish this purpose, IRBs use a group process to review research protocols and related materials (e.g., informed consent documents and investigator brochures) to ensure protection of the rights and welfare of human subjects of research” [3]. The IRB evaluates research protocols for safety and clarity. Some institutions use the IRB to evaluate studies for scientific merit and other institutions use other research committees to serve this function. A review of scientific merit will address ability of the study design to achieve the primary and secondary objectives and feasibility of the study. The primary and secondary objectives and the inclusion and exclusion criteria must be clearly stated. The study calendar identifies the timing of the study procedures and the study reports that are to be submitted. In designing a clinical trial, clear delineation of the components to the study are necessary to establish an effective monitoring or auditing program. The quality assurance program will be designed using the study parameters listed above to ensure research compliance and to ensure that the integrity of the study will be maintained allowing the primary and secondary objectives to be met. The audit or monitoring team works with the IRB representatives, the research staff, and the principal investigator to provide an assessment of the research integrity.

All quality assurance programs start with the study document and then create an auditing or monitoring program from that document that is in compliance with federal guidelines. The design of the study document plays a role in the future success of the quality assurance program. The integrity of the study is affected by the adherence to study protocols and procedures by the research sites. If a study is written in an ambiguous manner that is open to interpretation by the sites, there will not be consistency in the completion of the study parameters. The auditors or monitors will evaluate the research site’s compliance with study procedures using their understanding of the requirements of those ambiguous parameters. For example, a study may require two different imaging modalities to assess response to treatment such as CT scan and plain x-ray. If the study does not specifically define which imaging study is to be used to determine response, some sites will use the plain x-ray and others will use the CT scan. This will lead to variability in the study results, and if the auditors have been instructed that the response criteria are based on CT scan, then those sites that used plain x-ray will receive a deficiency. Similar issues arise when inclusion criteria and exclusion criteria are not well defined. For example, many studies require documentation that female participants are not pregnant. The study must specify what documentation is required for women who are postmenopausal or perimenopausal. If this is not adequately clarified, sites would have to complete pregnancy tests on elderly women to document definitively that the participant is not pregnant. All components of a study must be carefully evaluated from a quality assurance perspective for clarity to ensure that the proper participants are recruited and that the desired data points are collected in the manner intended by the study plan. This will enhance the integrity of the study and improve the quality assurance performance of all of the sites.

An investigator will be most successful in completion of a study when he has an interest in the topic being investigated. It is also crucial that the investigator have equipoise on the study question. If the investigator already believes that the study question has been answered, he is less likely to enroll subjects on the study particularly if there is a possibility that his patient will not receive a treatment that he feels is already established as more beneficial. Studies are also more successful when the investigators were involved in the design of the study. Participation in the design allows the investigator to participate in the selection of the endpoints and the variables to be tested.

When an investigator is evaluating a study for possible participation, it is important to not only evaluate the study for scientific merit but also for feasibility and clarity. If components of the study are unclear, the investigator should clarify those with the study sponsor before initiating the study. As the study moves forward, the investigator should continue to communicate with the study sponsor if there are any parameters that are ambiguous or unclear to the investigator. The experience of the organization sponsoring the study is also important to consider. Research organizations with less experience will write protocols that are not clear and therefore require more amendments. Each amendment will have to be submitted and reviewed by the IRB which increases the burden on the research site both for workload and ensuring compliance with the protocol changes. Completion of a clinical trial is a joint effort between the site and the study sponsors. The personnel at each group also play a role in successful completion of the study and in the overall data quality. The study personnel at the site may include the study coordinator, data manager, IRB staff, and the principal investigator. It is the responsibility of the principal investigator to ensure compliance with study policies and procedures and regulatory requirements. At sites with inexperienced staff, the oversight of the principal investigator is even more important. Principal investigators should have regular meetings with study personnel to review the study protocols and participant enrollments to ensure that all personnel involved in the study are meeting the study requirements.