What you should know about the ISS/ISE (ISR)

There are many reasons to integrate and to summarize all the data from a clinical trial program. Each clinical trial in the program is unique in its objective and design. Some are small safety studies among normal volunteers, while others are efficacy trials in a large patient population.

The primary reason to create an integrated summary is to compare and to contrast all the various study results and to arrive at one consolidated review of the benefit/risk profile.

A second and important reason is to reach a defensible statistical conclusion, through an exploration of the integrated data, that no competing alternative hypothesis that can reasonably account for the observed findings exists.

Third, pooling the data from various studies enables the examination of trends in rare subgroups of patients, such as the elderly, those with differing disease states (mild vs. severe), and those with comorbidities at baseline. Last, providing such a summary in the new drug application is required by the Food and Drug Administration (FDA) and other international authorities.


ISS will have all the clinical trial data, collected form a normal volunteers (from phase 1 study) and patients (all other studies).

ISE will have the clinical trial data only from the phase II and Phase III and phase IV and not of Phase I. The reason behind this is, Phase I study is conducted to identify the safety and not the efficacy of the drug, so the data from the Phase I study will not be there in the ISE.

ISE should have a description of entire efficacy database demographics and baseline characteristics.

ISS should have the details including the extent of the exposure of drug by the patient, different characteristics of patients enrolled in the study, listing the deaths occurred -during the study, How many patients are drop-outs from the study and Potential SAE, other AE and lab results.

ISS is considered as one of the most necessary document required for filing the NDA (new drug application). The safety data from different trials can be integrated by pooling all the safety data together and then to identify the AE, that are rare. The data integration approach for the ISS and ISE are entirely different, whereas pooling the efficacy data from different studies is not required, although pooled data will give more information regarding the efficacy of the drug. Pooling all the safety data is necessary in making the ISS. ISS needs a thorough research because it involves with the safety and safety parameter is considered important than the efficacy in a clinical trial, because study should always benefit patients.


ISR (integrated summary report):

It is a compilation of all the information collected from the safety and efficacy analysis in all the studies. ISS and ISE are different parts of ISR. Both the ISS and ISE reports are necessary for all the new drug applications (NDA) in the United States.

Every clinical trial is different, because each one is conducted for a specific purpose (Phase I for safety in normal population and all other for efficacy in patients).

The reason behind creating the ISR will be to create an integrated report to compare and to differentiate all other study results and to get one conclusion after reviewing the patient benefit/risk profile. It requires by the FDA is the other reason. Last but not the least reason for this is to reach a definite conclusion through thorough checking all the data which is integrated.


source: Encylcopedia of biopharmaceutical statistics page no: 486-489


INTEGRATED SUMMARIES OF SAFETY AND EFFICACY ( ISS AND ISE):




INTEGRATED SUMMARY of SAFETY REPORT




CTD – ISS/ISE: Introduction and Summary of Issues


Robert J. Temple, M.D.
Associate Director for Medical Policy
Center for Drug Evaluation and Research
U.S. Food and Drug Administration

Tips for Producing Comprehensive Integrated Summaries



Integrated Summaries of Effectiveness and Safety: Location Within the Common Technical Document