Integrated summary

Process Changes for Improved Heat Integration—Summary... 

Atkeson T, Axelrad D, Pollman C, Keeler G. 2003. Integrating atmospheric mercury deposition and aquatic cycling in the Florida Everglades integrated summary. Tallahassee (FL) Florida Department of Environmental Protection, p. 75-90. 

THE NATURE OF CHEMICAL PROCESS DESIGN AND INTEGRATION - SUMMARY... 

Mushak P, Crocetti AF. 1989. Determination of numbers of lead-exposed American children as a function of lead source Integrated summary of a report to the U.S. Congress on childhood lead poisoning. Environ Res 50 210-229. 

Therefore, if final, fully quality-assured individual study reports are not available at the time of IND submission, an integrated summary report of toxicological findings based... 

The NDA is a layered document. There are summary documents, individual study reports and actual data tabulations. It differs in two main ways from the dossier submitted in the European Union (1) in the amount of raw data contained in the NDA submission, and (2) in the presence of expert reports in the European dossier, compared with well defined integrated summaries in the NDA. This resulted from historical, cultural... 

These particular points relate to each individual trial, but equally there will be similar considerations needed at the level of the development plan. In order for the overall, ordered programme of clinical trials to be scientifically sound there needs to be a substantial amount of commonality across the trials in terms of endpoints, definitions of analysis sets, recording of covariates and so on. This will facilitate the use of integrated summaries and meta-analysis for the evaluation and presentation of the complete programme or distinct parts of that programme, and outside of that, will allow a consistency of approach to the evaluation of the different trials. 

Ensure quality and consistency of the individual reports, individual summaries, and integrated summary documents... 

The quality of a submission depends not only on the content of the submission but the tools provided to facilitate the review process. Now more than ever, FDA reviewers are receptive to electronic review aids and the use of electronic files. Simple and relatively inexpensive approaches are available. Important issues to consider during planning include the need for electronic review aids. These are electronic tools requested by the reviewer outside the electronic submission policy. Examples of these include book-marked, searchable versions of the integrated summaries and final clinical study reports for the core studies on CD-ROM or Microsoft Word versions of summaries that reviewers can cut and paste for their reviews. Since the preparation of the review summary can often be the longest part of the review, providing these tools can be useful in significantly reducing the total review time. 

Toxicology, including an integrated summary of toxicological effects of the drug, including results from acute, subacute, chronic, and in vitro toxicity tests, the effects on reproduction and the fetus and special toxicity tests. A detailed tabulation of toxicity data for each study should be included. 

Integrated summary of data from all studies and analysis of pertinent findings for interstudy and interspecies comparisons. Narrative summary for each study report describing the notable features and results of each study. A comprehensive study for notable findings in related studies for each species and notable species differences should be provided. 

Integrated summary of data from all studies and analysis of pertinent findings. 

Drug abuse and overdosage information Integrated summary of benefits and risks of the drug... 

An overall risk assessment should be included. This is intended to be a brief integrated summary that analyzes the preclinical and clinical data in relation to the potential risks and benefits of the proposed trial. Safety margins should be expressed on the basis of relative systemic exposure rather than applied dose. 

Moreover, although the regulation does not specifically require individual toxicology study reports to be submitted, referring only to an integrated summary of the toxicologic findings, the requirement for a full tabulation of data from each study suitable for detailed review has led most sponsors to provide detailed reports of each study. 

If the integrated summary is based upon unaudited draft reports, sponsors should submit an update to their integrated summary by 120 days after the start of the human studies identifying any differences found in the preparation of the final, fully quality-assured study reports and the information submitted in the initial integrated summary. If no differences were found, that should be stated in the integrated summary update. In addition, any new finding discovered during the preparation of the final, fully quality-assured individual study reports that could affect subject safety must be reported to the FDA as an IND safety report. 

Usually, 10 to 15 pages of text with additional tables as needed should suffice for the integrated summary. It should represent a perspective on the completed animal studies at the time the sponsor decided that human trials were appropriate. Use of visual data displays (e.g., box plots, histograms, or distribu-... 

The integrated summary of the toxicologic findings of the completed animal studies to support the safety of the proposed phase 1 human investigation should ordinarily contain the following information ... 

It should be noted that the information described in the last three points may be supplied as part of the integrated summary or as part of the full data tabulations described in the next section. 

An applicant may provide an overall summary of data from controlled studies. This section is optional and many firms do not include it because the results of the studies are presented in the integrated summaries of efficacy and safety, which will be discussed later in this chapter. The Guidelines for the Clinical and Statistical Sections of a New Drug Application also address the format and content of an integrated clinical/statistical report for a clinical study this too will be discussed later. 

This section should provide an integrated summary of the data demonstrating substantial evidence of effectiveness for each claimed indication. It should also include a summary of the evidence supporting the dosage and administration section of the labeling, including the dose and dose interval recommended. 

An analysis of responses in subsets of the overall population is required. The extent of this part of the integrated summary of efficacy will depend to a large extent on the drug and its intended patient population. Subsets of interest may include sex, race, age, disease severity, concomitant illness, concomitant drugs, smoking and alcoholism, and prior therapy. 

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