This one-day course will provide attendees with an in-depth review of the Clinical Research process, including investigator responsibilities, adverse event (AE) reporting, Data & Safety Monitoring and Good Documentation practices for a clean audit all designed to protect the safety of human subjects and to ensure data integrity. The Selected Topics are Important to those in the Clinical Research Industry who conduct or otherwise are involved in research studies involving human subjects.

1. The Secret of Study Conduct Documentation to ensure a successful Audit: What the Inspectors / Auditors look for

Overview: All Clinical Research protocols have the procedures and processes needed to collect the data as it happens. The FDA guidelines and regulations for the conduct of research involving human subjects were developed to ensure complete and credible data and, of course, to safeguard the health and safety of human subjects. This is further emphasized in the ICH E6 2.10: "All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification", which will allow the creation of a clear and followable data trail. The rules of collecting, correcting, and caring for all original (source) documents must be known by the entire study staff under the direction of the PI. In the end, the entire investigation team is charged with ensuring that the data obtained from trial subjects is accurate and valid. The presentation lays this on the table.

2. How does a Research Site get the Principal Investigator Involved and how this involvement / commitment affects study Conduct

Overview: When the PI signs the FDA form 1572 (for IND studies) or the "Statement of the Investigator (for IDE studies), she / he is signing a legally binding document committing themselves to follow all of the appropriate regulations. Named in the 1572 is 21 CFR 50 (Protection of Human Subjects), 21 CFR 56 (Institutional Review Boards), and 21 CFR 312 (Investigational New Drug Application / IND). For Device studies, 21 CFR 812 (Investigational Device Exemptions / IDE) is added in place of 21 CFR 312. Additional responsibilities are clearly outlined in The GCP Guidelines of E6 (4), the Compliance Program Guidance Manual (CPGM) 7348.811, and the new (October 2009) Investigator Responsibilities Guidance document. To follow the regulations is Good Clinical Practices (GCP) and common sense. To not know and follow these regulations is folly

3. Why is Accurate Adverse Event Reporting essential for drug safety - How to Identify, Assess and Report AEs and SAEs

Overview: The principal objective in a new drug development program is to assess the benefit / risk ratio. Therefore risk information must be collected, documented and reported accurately. The single most important function of the Principal Investigator and the study conduct team is the awareness, assessment, and management of Adverse Events occurring during the conduct of clinical research with drugs or devices utilizing human subjects. AE’s are one of the key ways the Clinical Investigator has of monitoring the safety of subjects or patients in her/his charge. To obtain 'commonality' in reporting investigative sites require familiarity with one of the Adverse Event Terminology systems such as MedDRA. As codified in 21 CFR 312.64(b), an investigator shall promptly report to the sponsor any adverse event that may reasonably be regarded as caused by, or probably caused by, the drug. Determining the relationship between the study drug and an AE requires a practiced power of observation & great care (good medical judgment).

4. Why Study Participant / Patient Recruiting is Vital to Success in Clinical Research and how to insure this success.

Overview: The ability to bring in (recruit) on-time study participants whether they be ‘normal healthy adults” or patients with the condition being studied is essential for a CRO, a site, a CPU/CRU for conducting on-time study starts with the full complement of volunteers. For this reason the recruiting process is a top priority of those in management including the PI. The challenges are many but, in the end, it is following the logical steps of the recruitment process that is paramount to a full and on-time study start. First a plan must be developed for each study based on the particular protocol at hand. Second, a strategy must be chosen based on resources’ available and the usual barriers from a complex protocol to study participant mistrust of research. Then the plans of how you are going to reach potential volunteers and track the results must be implemented.

5. What is the role of Data and Safety Monitoring in Clinical Research Involving Human Subjects – When are these committees needed and how are they set-up

Overview: All Clinical Research protocols have a prominent safety monitoring “plan” as part of the overall research plan / protocol. This "plan" is to ensure the safety of participating subjects and to ensure the validity and integrity of the data. Safety monitoring is mandated in 21 CFR 312.50, 312.56, and 600.80 for drugs and biologics and 21 CFR 812.40 and 812.46 for devices Depending on the nature of the test agent, the length of the study or the number of sites conducting the clinical study, the "Plan" may set the "Charter" of what is called a Data and Safety Monitoring Board (DSMB) or Committee (DMC). DSMB's and their composition play an increasingly important roll in both multi-center studies and where there are expected or possible adverse events. The "Stopping Rules" are an important element in the Charter. The overriding reason for a carefully selected DSMB is to promote and guarantee human subject safety as well as data integrity.

6. Your Choice - TBD

• How does compliance with 21 CFR Part 11 help ensure data integrity and subject safety in Clinical Research. (A review of electronic data processing for the non-computer geek)

• What is the latest on how to go through an FDA inspection? (a review of how to be audit ready and thoiughts from the recent 2009 FDA Inspections Summit)