In Keeping With The FDA’s Regulatory Environment
The FDA and the ICH both have similar requirements for designing clinical protocols. These protocols are outlined by the FDA’s regulatory environment. The regulation outline is consistent with developing protocols which are scientific in nature, promote safety, and clinical transparency.
Regulatory Framework for Level of Evidence and Study Design
3.1 The Statutory Standard for Approval of a PMA: Reasonable Assurance of Safety and Effectiveness
3.2 Valid Scientific Evidence
3.3 Benefit-Risk Assessment
3.4 Clinical Study Level of Evidence and Regulation
3.5 The Least Burdensome Concept and Principles of Study Design (FDA, 2013).
Under guidance 3.1 The Statutory Standard for Approval of a PMA: Reasonable Assurance of Safety and Effectiveness, a clinical trial must be designed with a reasonable assurance of safety and effectiveness. This is a specific regulation which is specific to the persons or group who will be using the device or drug. As well as person specific, the regulations also require that the conditions of use such as prescription, dosages, and other recommendations must be listed. As well, a risk benefit analysis must be created (FDA, 2013).
Under Guidance 3.2 Valid Scientific Evidence, a clinical trial must be designed such that all findings are based on scientific evidence. Valid scientific evidence is defined as “evidence from well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts” (FDA, 2013) This requirement for scientific evidence provides a clear overview of the workings of the device or effects of a drug which can be analyzed and replicated in other studies.
The risk benefit analysis, under FDA guidelines requires specific information concerning the drug or device being tested. The design of the clinical study must show the following information:
· the type of benefit(s),
· the magnitude of the benefit(s),
· the probability of the patient experiencing one or more benefits, and
· the duration of effect(s).
· Factors that FDA takes into account when considering the extent of probable risk(s) or harm(s) include:
· the severity, types, number, and rates of harmful events associated with the use of the device,
· the probability of a harmful event,
· the duration of harmful events, and
· the risk from false-positive or false-negative results for diagnostic devices (FDA, 2013).
This same risk assessment is defined under ICH Q9 Quality Risk Management which is handled as a risk assessment of the drug or device (FDA, 2015). There are more guidelines with ICH due to this method of analysis. The ICH looks to cover potential dangers as well as dangers reflected in research. However, both the ICH and the FDA require that the design of the trial be backed by research and evidence that conforms to scientific standards. This is stressed in ICH Q9 and other sections of the ICH protocols as well as in the FDA3.4 Clinical Study Level of Evidence and Regulation (FDA, 2015).
Another area comparison between the ICH and the FDA clinical design requirements is the focus on ethics. The ICH and the FDA both stress ethics but the ICH has a larger more comprehensive view which takes into account a variety of factors such as collection of foreign data and informed consent. This difference is understandable due to the ICH being focused on international standards whereas the FDA is more concerned with regulatory compliance and ethics focused on domestic studies.
FDA. (2013, Novemeber). Design Considerations for Pivotal Clinical Investigations for Medical Devices — Guidance for Industry, Clinical Investigators, Institutional Review Boards and Food and Drug Administration Staff. Retrieved from Food and Drug Administration: http://www.fda.gov/RegulatoryInformation/Guidances/ucm373750.htm
FDA. (2015). ICH Guidance Documents. Retrieved from Food and Drug Administration: http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsandNotices/ucm219488.htm