If you have clinical data for your product, then your goal for this sub-section is to provide the FDA with concise data summaries along with key learnings and findings from your studies. Remember, full study reports or detailed data sets are generally not appropriate for Pre-IND meeting information packages. Consider dividing your information into the following three sub-sections:
Natural history studies
Prior clinical experience
Planned/Upcoming clinical studies
Continue reading to learn more about what you can include under each.
Natural history studies
It may be helpful to include natural history studies to provide the scientific foundation upon which your product development program can be built. Additionally, the data from the studies can be more informative in the Pre-IND phase to help design efficacy trials.
What is a natural history study?
A natural history study collects information about the natural history of a disease in the absence of an intervention, from the disease's onset until either its resolution or the individual's death. Its purpose is to identify demographic, genetic, environmental, and other variables (e.g., treatment modalities, concomitant medications) that correlate with the disease’s development and outcomes.
Although the knowledge of a disease's natural history can benefit drug development for many disorders and conditions, natural history information is usually not available or is incomplete for most rare diseases; therefore, natural history information is particularly needed for these diseases.
In addition to natural history studies being highly encouraged for rare disease by the FDA, there are ways in which they can help you in your clinical development plan. These have been summarized into four sections below. (If you are curious to know more about natural history studies and how exactly they tie into your clinical development plan, the FDA has specific guidance you can find here: Rare Diseases: Natural History Studies for Drug Development | FDA). [11]
Benefits of natural history studies | ||
|---|---|---|
Identifying the patient population A well-designed natural history study may be useful in understanding which patient subgroup(s) may benefit from a particular drug trial |
| Identification or development of Clinical Outcome Assessments A natural history study can help evaluate the ability of a new or existing COA to detect change in a particular disease or a pattern of progression of a disease or symptoms of disease |
Identification or development of biomarkers A natural history study can help identify/develop biomarkers that can be diagnostic of the disease, prognostic of the disease’s course, predictive of treatment response, or useful in guiding patient selection and dose selection in drug development programs | Design of externally controlled studies Data and information from a natural history study may provide an untreated, external control group for use as the comparator to the treatment group(s) in an investigational drug trial | |
Prior clinical experience
In the event that there is clinical data from your product, then it is recommended for you to include a summary of the key learnings and findings along with key data sets under this sub-section. If more than one study has been conducted, separate the section out by each study. To ensure you are effectively communicating all aspects of the study conducted, consider following the outline below for each:
Study title
Study objectives and criteria for evaluation
Methodology
Diagnosis and main inclusion criteria
Treatment arms and dosing regimen
Study results (For easier visualization of your data, consider having it in a tabular or graphical format)
Study site/s
Drug manufacturing site
You can include your study reports in the appendix section of your Pre-IND MIP.
Planned/Upcoming clinical studies
Before moving on, it is recommended that you conclude the sub-section with a summary of any planned/upcoming IND opening clinical study. This will be the critical part of the clinical section. This includes providing the FDA with a clinical study synopsis or draft outline for the studies that you plan to conduct in your clinical development plan. Consider a tabular description of all study-related events and assessments, including, but not limited to:
Investigator/study center
Trial design
Subject screening and enrollment (e.g., patient population or healthy normal controls, inclusion, and exclusion criteria)
Safety assessments
Efficacy evaluations
Pharmacokinetics sampling (e.g., immunogenicity markers, viral vector shedding, other laboratory detectable metabolites, biomarkers if applicable)
Route of administration
Proposed treatment regimen
Stopping rules (a set of criteria that specify when dosing an individual subject, cohort and/or trial should be suspended)