Finally, just because a laboratory has analyzed a sample and generated a report does not mean the data have been successfully transferred to the sponsor. How does the lab send the data? By FedEx? By email? In what format is the report? Is it a printed form or a spreadsheet? This is a stage of data handling and needs quality control with written procedures.

Clinical labs are often very large places. Therefore, it is important not to get lost when conducting an audit. To avoid getting lost, focus on the areas important to the specific study.

It is worth noting that there is one place that clinical laboratories are subject to GCP regulations. The investigator is required to maintain adequate and accurate subject case histories.⁸ Laboratory reports are frequently part of those case histories, which is one reason why the investigator needs to list the clinical lab on Form FDA 1572 required by regulation.⁹

Site management organizations

Many sponsors are using SMOs in an effort to improve subject recruitment and GCP compliance. However, it is a mistake to think that SMOs are regulated the same way as CROs. In fact, the regulations treat them both quite differently.

Why is this the case? It is a question of responsibility.¹⁰ Where the regulations allow the sponsor to contract certain responsibilities, they require the investigator to "personally conduct or supervise" the study.¹¹ Since the SMO contracts with the investigator and not the sponsor, it assumes responsibilities assigned to the investigator in GCP regulations.

Most SMOs provide study coordinators and other study staff. Staff members often participate in the recruitment of subjects and obtain informed consent.¹² Study staff will maintain study records, including disposition of the study drug/device¹³ and subject case histories. These are specific regulatory responsibilities of the investigator. If the FDA has a problem with the conduct of the study, it is the investigator, not the SMO, who receives regulatory correspondence, including a warning letter, from the FDA. This should be understood by every investigator prior to subject enrollment.

An SMO may have functions that are contracted responsibilities of the sponsor. These functions include the selection of a qualified investigator to conduct the study, test article accountability, and safety reporting.¹⁴ If an SMO has contracted with the sponsor or subcontracted with a CRO to perform regulatory responsibilities, then it can be held accountable by FDA. This certainly can be confusing. It's a question of responsibility—so the sponsor, investigator, and any contractors need to know exactly where responsibilities lay. This makes the auditing and qualification of an SMO a challenging task. Let's break things down into manageable portions.

SMO breakdown. An SMO is going to be critical to both data integrity and the protection of human subjects. Sometimes both of these FDA concerns are addressed in the same function. When a study coordinator elicits adverse events from a subject, there is concern regarding whether the data are accurate. There is also concern regarding whether the safety of participants in a clinical trial is being reviewed and addressed by the investigator or some other individual. So a primary concern should be the qualification of study staff.

Originally, most study coordinators were registered nurses. Nurses are trained to elicit adverse events from patients and know when to refer issues to a physician. Currently, study staff members are frequently not licensed medical professionals and there are no regulations that require an investigator to use nurses or other licensed health care workers. So it is important to examine how the investigator will delegate responsibility and supervise the trial. This should be established prior to subject enrollment and be periodically reviewed by monitors and auditors throughout the study. In addition, it still is important to have quality control with written procedures for each stage of data handling.