Integrated Summaries (ISS/ISE) are often required by health authorities when submitting a new drug application. It is important to note that integrated summaries are not simply study summaries, but rather they are an analysis of results that determine the safety and effectiveness of drugs in development. ISS and ISE are also an integral part of the Common Technical Document. CROS NT discusses how to get full value from integrated summaries.
The FDA requires both ISS and ISE for New Drug Applications and an electronic submission of a CTD. In Europe, the EMA requires ISS and ISE for regulatory submissions and new drug applications. Integrated Summaries for European submissions include not only statistical analyses of safety data and meta-analyses of efficacy data, but also expert medical writing.
Avoiding High Charges from CROs for Integrated Summaries
Costs associated with integrated summaries can be astounding – from documentation, submission, statistical analysis and programming to meeting tight timelines. Therefore, how can these costs be reduced?
The biggest impact on costs is timelines. Reducing time and being more efficient will inevitably reduce costs. Centralizing clinical data can be the first step towards reducing time and costs. Having data management, statistics, programming and medical writing services with the same specialist provider will allow for data traceability, data quality and, in terms of cost, an economies of scale model for services provided.
Consistency is the key in ensuring that integrated summary preparation goes as smoothly as possible. This means that the clinical data aspect of the study should also be consistent and ideally centralized for maximum collaboration. Since integrated summaries provide statistical evidence based on consolidated data to support an analysis of the benefits and risks of a drug in development, the methodological biostatistician should be involved at every step. This guarantees consistencies in the dataset variable which makes for swift and efficient preparation.
Another way to reduce costs is through standardization. This includes using similar structures for datasets, for example, CDISC standards. Standardization is also applicable to reporting and using standard formats for tables, figures and listings, CDISC guidelines can be useful when preparing integrated summaries from a statistical perspective. According to ICH guidelines for electronic CTD submission, CDISC Study Data Tabulation Model (SDTM) is preferred. The CDISC-compliant Analysis Data Model (ADaM) for statistical analysis in integrated summaries is also supported. Statisticians and programmers who are familiar with CDISC methods are at an advantage when preparing integrated summaries.
As planning is an important step in preparing integrated summaries, there should be a good communication plan defined between the CRO and the Sponsor. Agreeing on a statistical analysis plan, methodologies and programming formats can reduce the number of reviews, therefore saving time and costs.
As drug development companies complete ISS/ISE as part of New Drug Applications, they do not need to face exuberant costs from the CRO. Centralizing clinical data and working closely with the methodological statistician from the early planning phase can reduce timelines and eventually costs.
Need support with Integrated Summaries preparation? Consult one of our expert biostatisticians.