Importantly, for any new company to perform clinical research they must first obtain an IND from the FDA. This is the license it allows for controlled human testing to proceed (done by GCP, good clinical practice standards). The FDA’s chief concern is safety of human subjects for which they will evaluate carefully especially concerning:
- CMC – The manufactured product must meet certain specifications to show it is safe. We will discuss CMC more in future blogs.
- Clinical plan – The initial protocol for the initial clinical trial is included in the IND submission. It must include the following design features (please see CFR21 sec 312.23 for a more complete description) so examine the protocol generally for the following information:
- Purpose statement of the study
- Inclusion and exclusion criteria
- Inclusion criteria should carefully define the population in whom efficacy and safety of the medicine for the desired indication will be tested.
- Exclusion criteria should remove subjects from consideration who would diminish the validity of the trial results or for whom the study would be unsafe. Be careful though, if possible, not to have so many exclusions that recruiting becomes problematic and increases costs in time and money.
- Design – This section includes the type of control group to be used, if any, and a description of methods used to minimize bias on the part of subjects, investigators, and analysts.
- Dose justification – This section provides the rationale for determining the administered dose(s), the planned maximum dosage, and the duration of individual patient exposure to the investigative product. Justification should be derived generally from the GLP toxicology study primarily, as well as from preclinical studies for efficacy, safety and PK. Dose justification will have been included in the IND document.
- Clinical measures – This is a description of the observations and measurements to fulfill the goals of the study. Carefully consider the following measures:
- Primary efficacy variable – This should be a common and well accepted clinical measure of the targeted disease. Further the FDA should have approved the use of this variable and clinical its measures in the IND. Likewise the method of measure should be well accepted by the clinical community and the FDA as a relevant measure of the status and changes in the targeted disease.
- Additional tests – The protocol should include a description of additional clinical procedures, laboratory tests, or other measures used to monitor the potential effects of the drug in human subjects and to minimize risk. These tests should especially include safety measures that might be anticipated based on preclinical studies including GLP toxicology, CMC issues and potential adverse events based on prior research, clinical reports or the mechanism of action of the medicine.
- Sample size – For an initial study, which would be Phase I or II, the number of subjects based on the study medicine in ophthalmology is typically between 40 and 200. In these early studies the sample size is often not statistically powered. Regardless, the sample size should be justified to the FDA that it will show initial safety, possibly a clinical effect while not over-exposing unnecessarily too many subjects to an experimental medicine.
- Dosing level and frequency
That is enough for now! The next blog will talk about GCP and trial conduct. Thanks for joining me. I look forward to seeing you next time.
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