24. Aggregate reporting- IND annual reports

Investigational New Drug (IND):

Once the preclinical stages including the required short term animal studies have been completed, the drug is ready to be moved into human testing. Before this can happen permission for human research must be obtained by submitting an Investigational New Drug (IND) application to the Food and Drug Administration (FDA). An IND application is a request for authorization from the FDA to administer an investigational drug or biological product to humans. 

IND annual report:

An IND Annual Report is required to be submitted in yearly intervals within 60 days of the anniversary date of the IND effective date. This report is required annually until the final Clinical Study Report for studies filed under the IND has been submitted to the FDA or the IND has been withdrawn. Some of the IND Annual Report required information includes a brief summary status of each study in progress or completed during the previous year and the safety of the drug as defined by adverse event tables and listings. This brief report concentrates on the safety of the drug is IND Annual Report (IAR). 

Sections of IND annual report:

Section 1: Individual Study Information

A brief summary of the status of each study in progress and each study completed during the previous year. The summary is expected to include the following information for each study: 

1. The title of the study (with any appropriate study identifiers such as protocol number), its purpose, a brief statement identifying the patient population, and a statement as to whether the study is completed.
2. The total number of subjects initially planned for inclusion in the study; the number entered into the study to date, tabulated by age group, gender, and race; the number of participants who completed the study; and the number who dropped out of the study for any reason.
3. A brief description of any available study results.

Section 2: Summary Information:

Information obtained during the previous year’s clinical and nonclinical investigations conducted under the IND application, including: 

1. A narrative or tabular summary showing the most frequent and most serious adverse experiences by body system.
2. A summary of all IND safety reports submitted during the past year.
3. A list of subjects who died during participation in the investigation, with the cause of death for each subject.
4. A list of subjects who dropped out during the course of the investigation in association with any adverse experience, whether or not thought to be drug related.
5. A brief description of what, if anything, was obtained that is pertinent to an understanding of the drug’s actions, including, for example, information about dose response, bioavailability, or relevant information from controlled trials.
6. A list of the preclinical studies (including animal studies) completed or in progress during the past year and a summary of the major preclinical findings.
7. A summary of any significant manufacturing or microbiological changes made during the past year.

Section 3: General investigative plan for next year 

1. Rationale 
2. Indications
3. General Plan
4. Planned Trials/Expected Subject Recruitment 
5. Anticipated Risks of Particular Severity 

Section 4: Investigator Brochure updates

Section 5: Significant protocol updates – A description of any significant Phase 1 protocol modifications made during the previous year and not previously reported to the IND in a protocol amendment 

Section 6: Summary of foreign marketing experience – A brief summary of significant foreign marketing developments with the drug during the past year, such as approval of marketing in any country or withdrawal or suspension from marketing in any country

Section 7: Outstanding business – If desired by the sponsor, a log of any outstanding business with FDA with respect to the IND application for which the sponsor requests or expects a reply, comment, or meeting.

The following are examples tables:

Note: To promote global harmonization, FDA has indicated that it will accept DSURs instead of IND Annual Reports as long as they have all the requirements of the US Annual Report in the region specific appendices of the DSUR.