An independent safety officer (ISO) is a clinician or researcher who is independent of the clinical study team and helps to monitor a clinical trial for research participant (patient) safety, adverse events, trial progress, and data quality. An ISO has relevant experience with clinical trials as well as with the patient population and intervention being studied. Clinical trials using an ISO are usually smaller, single-site trials with a moderate to minimal risk intervention.
Safety surveillance of a clinical trial should be in proportion to the risk and complexity of the trial. [1] [2] Large, multi-site clinical trials are commonly overseen by a Data Monitoring Committee or Data and Safety Monitoring Board (DSMB) consisting of expert clinicians, biostatisticians, and ethicists or patient advocates. [3] [4] Small, minimal risk studies may be monitored by the principal investigator according to the data and safety monitoring plan (DSM plan) approved by the institutional review board (IRB). [5]
For clinical trials with intermediate complexity or risk, the use of an ISO can be very helpful to monitor the trial for research participant safety, adherence to the protocol, and collection of good data. Examples of studies monitored by an ISO might include a trial involving Food and Drug Administration (FDA) approved drugs used in unapproved indications, [6] non-significant risk medical devices, nutritional products used as a drug, research-only interventions such as an insulin clamp, or behavioral interventions with the possibility of psychological adverse events. Monitoring by an ISO may also be appropriate for higher risk single-site studies of short duration, such as pilot studies, for which convening a full DSMB is not feasible. [7]
An ISO is usually a physician or investigator with experience and training in both the disease and the intervention being studied. This allows the ISO to assess the safety of the research participants throughout the course of the trial. In addition, an ISO has experience with clinical trials so that they can monitor the progress of the trial for adequate enrollment, appropriate follow-up, adherence to protocol, and good data collection. Finally, the ISO is independent of the clinical trial they are monitoring. They are not a part of the study team and have no financial or scientific conflicts of interest with the clinical trial or the principal investigator. [7] [8]
The DSM plan, which is approved by the IRB before a trial begins, will stipulate the use of an ISO for monitoring. In addition, the specific responsibilities of the ISO for that trial are defined by the ISO charter written by the principal investigator and the ISO. The charter typically sets out the aspects of the trial that will be reviewed, the frequency of data review and written reports, a plan for adverse event identification and reporting, a plan for monitoring of data quality and accuracy, and the criteria for decision-making regarding continuation, modification or termination of individual participants or the clinical trial. [5]
An ISO meets regularly with the principal investigator and study team to review the progress of the trial. In these meetings, the ISO discusses: 1) a review of any adverse safety events; 2) protocol deviations and exclusions; 3) enrollment and follow-up of participants; 4) missing data and data quality controls; 5) any new medical advances that may require changes in the study protocol. The timing of the meetings depends on the risk to the participants as well as the degree of oversight needed for a particular trial. [7]
If a clinical trial has regulatory lapses, excessive adverse events linked to the trial intervention, or fails to recruit adequate numbers of participants, the ISO may recommend that the clinical trial protocol be modified or the trial terminated.
Occasionally, additional expertise beyond the ISO is needed to accomplish a comprehensive review. With additional personnel, this is considered a Safety Committee. Most frequently a biostatistician will be the additional reviewer. Other additions can include a content expert for nonclinical issues, a methodology consultant, or another clinician that has additional specific expertise. [5]
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted.
In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. In some cases, while blinding would be useful, it is impossible or unethical. For example, it is not possible to blind a patient to their treatment in a physical therapy intervention. A good clinical protocol ensures that blinding is as effective as possible within ethical and practical constraints.
Pharmacovigilance, also known as drug safety, is the pharmaceutical science relating to the "collection, detection, assessment, monitoring, and prevention" of adverse effects with pharmaceutical products. The etymological roots for the word "pharmacovigilance" are: pharmakon and vigilare. As such, pharmacovigilance heavily focuses on adverse drug reactions (ADR), which are defined as any response to a drug which is noxious and unintended, including lack of efficacy. Medication errors such as overdose, and misuse and abuse of a drug as well as drug exposure during pregnancy and breastfeeding, are also of interest, even without an adverse event, because they may result in an adverse drug reaction.
An institutional review board (IRB), also known as an independent ethics committee (IEC), ethical review board (ERB), or research ethics board (REB), is a committee at an institution that applies research ethics by reviewing the methods proposed for research involving human subjects, to ensure that the projects are ethical. The main goal of IRB reviews is to ensure that study participants are not harmed. Such boards are formally designated to approve, monitor, and review biomedical and behavioral research involving humans, and they are legally required in some countries under certain specified circumstances. Most countries use some form of IRB to safeguard ethical conduct of research so that it complies with national and international norms, regulations or codes.
Clinical monitoring is the oversight and administrative efforts that monitor a participant's health and efficacy of the treatment during a clinical trial. Both independent and government-run grant-funding agencies, such as the National Institutes of Health (NIH) and the World Health Organization (WHO), require data and safety monitoring protocols for Phase I and II clinical trials conforming to their standards.
A serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose
An investigational device exemption (IDE) allows an investigational device to be used in order to collect safety and effectiveness data required to support a premarket approval (PMA) application or a premarket notification [510(k)] submission to Food and Drug Administration (FDA). Clinical studies are most often conducted to support a PMA. Only a small percentage of 510(k)'s require clinical data to support the application. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated.
Good clinical practice (GCP) is an international quality standard, which governments can then transpose into regulations for clinical trials involving human subjects. GCP follows the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), and enforces tight guidelines on ethical aspects of clinical research.
A data monitoring committee (DMC) – sometimes called a data and safety monitoring board (DSMB) – is an independent group of experts who monitor patient safety and treatment efficacy data while a clinical trial is ongoing.
A case report form is a paper or electronic questionnaire specifically used in clinical trial research. The case report form is the tool used by the sponsor of the clinical trial to collect data from each participating patient. All data on each patient participating in a clinical trial are held and/or documented in the CRF, including adverse events.
In drug development and medical device development the Investigator's Brochure (IB) is a comprehensive document summarizing the body of information about an investigational product obtained during a drug trial. The IB is a document of critical importance throughout the drug development process and is updated with new information as it becomes available. The purpose of the IB is to compile data relevant to studies of the IP in human subjects gathered during preclinical and other clinical trials.
In natural and social science research, a protocol is most commonly a predefined procedural method in the design and implementation of an experiment. Protocols are written whenever it is desirable to standardize a laboratory method to ensure successful replication of results by others in the same laboratory or by other laboratories. Additionally, and by extension, protocols have the advantage of facilitating the assessment of experimental results through peer review. In addition to detailed procedures, equipment, and instruments, protocols will also contain study objectives, reasoning for experimental design, reasoning for chosen sample sizes, safety precautions, and how results were calculated and reported, including statistical analysis and any rules for predefining and documenting excluded data to avoid bias.
Cancer and Leukemia Group B is a cancer research cooperative group in the United States.
A Clinical Research Coordinator (CRC) is a person responsible for conducting clinical trials using good clinical practice (GCP) under the auspices of a Principal Investigator (PI).
A glossary of terms used in clinical research.
The following outline is provided as an overview of and topical guide to clinical research:
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for drug safety in a few human subjects, then expand to many study participants to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays.
Ansuvimab, sold under the brand name Ebanga, is a monoclonal antibody medication for the treatment of Zaire ebolavirus (Ebolavirus) infection.
A platform trial is a type of prospective, disease-focused, adaptive, randomized clinical trial (RCT) that compares multiple, simultaneous and possibly differently-timed interventions against a single, constant control group. As a disease-focused trial design, platform trials attempt to answer the question "which therapy will best treat this disease". Platform trials are unique in their utilization of both: a common control group and their opportunity to alter the therapies it investigates during its active enrollment phase. Platform trials commonly take advantage of Bayesian statistics, but may incorporate elements of frequentist statistics and/or machine learning.
