Conducting the study
Once participants are enrolled, the study team can start to conduct the study and collect the data. The conduct of the study follows the procedures outlined in the study protocol as well as applicable guidelines, regulations, and standards.
A study team can include physicians, nurses, data managers, data entry specialists, pharmacists, laboratory support staff, administrative support staff, statisticians, patient advocates, and others. The team collects information (such as medical history, physical examination results, responses to questions, results of imaging studies) and biological specimens (such as blood samples, tissue samples, genetic tests) from participants according to the schedule described in the study protocol and the procedures described in the study’s Manual of Operations. Each study participant receives a detailed schedule of when data will be collected and what each visit involves; the study team arranges follow up and provides on-going education. Participant information is captured in the study’s data collection system (sometimes using specific forms, called “case report forms”), which can be paper or electronic.
The study team will meet periodically to review accrual, discuss progress, and address any problems. Adjustments to the study procedures may occur, including revisions of the protocol if necessary.
Monitoring the study
To ensure that study participants are protected and to ensure the integrity of the data being collected, studies are monitored while they are taking place. For instance, researchers are expected to follow applicable guidelines and standards when conducting a clinical study:
Data and Safety Monitoring Committee
The FDA describes situations in which a Data and Safety Monitoring Committee is used and provides recommendations on procedures and process in its guidance on Data Monitoring Committees
. For example:
- The role of the Board or Committee is established before a clinical trial begins. Its functions typically include review of the protocol before it is implemented, review of study implementation and progress, and ongoing review of the accumulating data to detect evidence of early, significant benefit or harm for participants while the trial is in progress. This latter review serves as an additional protection for participants, beyond that provided by the IRB, but does not take the place of regulatory requirements for investigators to report serious and unanticipated adverse events to the FDA.
- The committee is normally responsible for defining its meeting schedule, based on the study's enrollment rate and the potential risk to participants.
- It may also establish "stopping rules" for halting the study based on:
- How great a difference in effects is required to demonstrate clear clinical significance and make the data convincing to clinicians, and
- Statistical techniques designed to preserve the final significance level of the trial.
- Who serves on the Committee depends on the research question and the funding mechanism of the study. Some mechanisms have these Committees built-in to their networks; other times, the Committee monitors the specific trial, so their membership is tailored to the expertise specific to that trial(s). Other features of the Committee include:
- Five to seven members, including one or more of the following individuals: clinicians with expertise in the specific disease and/or treatment under study, biostatisticians, epidemiologists, and ethicists/patient advocates.
- Members may also include a clinical researcher and a representative from the IRB.
- Normally, members are not employees of the NIH or from the same institution as the principal investigator (PI).
The Data and Safety and Monitoring Committee or Board may meet on a regular basis in either "open session" or "closed session." NICHD staff who participate in the trial as investigators do not attend "closed sessions" during which safety and efficacy data are reviewed; however, staff who are representing the interests of NICHD or who are program officials attending in an ex officio
capacity may attend such sessions.
NICHD staff may attend "open sessions" to provide the Committee with relevant updates in the field under study that might impact the Committee’s deliberations, to supply additional details on implementation or conduct of the trial, and to answer questions from Committee members.
The Committee recommends continuation, modification, or termination of the trial after each meeting. These recommendations are usually reported to the NICHD, any additional study sponsors, the clinical investigators, any data coordinating centers and the IRBs of participating institutions. through an established information flow. Typically the recommendations are accepted and implemented.
Resources for conducting and monitoring the study
- ICH Guidelines
- FDA Guidelines
- NIH Guidelines
- Office of Human Research Protection
- NICHD Guidelines
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