Commercial Deliverable R&D

Target Product Profile (TPP)

What is a Target Product Profile (TPP)?
A target product profile refers to what the expected properties of a drug will be once development (ie studies) are complete. It usually consists of many elements including information on expected dosing, route of administration, potential efficacy and safety profile, etc. As new data emerge once studies readout the TPP is generally updated to reflect the latest knowledge.

The TPP is an important strategic tool used within pharma companies to plan for and assess investigational agents including the market potential, potential marketing strategies, etc. It is also important to levelset between various functions and can serve as a potential base case to compare actual results against. Finally, TPPs can be shared with regulatory authorities in earlier discussions as study design and other decisions are being talked through and made.

Deliverable R&D

Clinical Study Report (CSR)

What is a Clinical Study Report (CSR)?
A Clinical Study Report (CSR) is a key deliverable that is required in many regulatory submissions and containing information about the methods and results of a clinical trial or clinical study. The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) provides an E3 guidance which orders the structure of the information presented within the document.

This information includes specifics on the proposed course of treatment, the medical information derived from the patients, patient demographics, and other information that gives insight into the trial methods and results. Specifically, it starts with a summary of the content to be presented within the document followed by a methodology section. Next, the results and data that were collected are presented followed by conclusions about the data. Safety and efficacy results and/or pharmacodynamic and pharmacokinetic results may be found in CSRs depending on what the aims of the specific study were. Section 14 consists of all the TFLs (tables, figures, and lists) which organizes the data from the results. Section 16 is an appendices section and can include any other documents that are required or are related to the report.

This document is mainly written by a medical writer but at times, a statistician can be a part of writing certain sections such as the efficacy results. The data presented in the TFL is what is used by the medical writer to analyze and describe in the CSR. Multiple cross-functional team members will work on the document, and it will most probably go through several drafts before being submitted with each subject matter expert serving as a reviewer for their relevant sections (eg Clinical Development personnel would ensure the trial design is properly described).

CSRs help provide the final key piece of information about a clinical trial for regulators. While they would have seen the study protocol and other information on trial design and the statistical analysis plan prior to study commencement and data collection, the CSR is generally the first time they are seeing detailed overviews of the results. Regulators use the information that is provided to assess the outcome of the clinical studies. CSRs are very long documents as they are highly technical and detailed. A short summary of a CSR known as a CSR synopsis which touches on important points such as where the trial was conducted, phase of the study provided, length of study, the participants, and the objective of the study is also produced for a quicker high-level read of what is in the broader document.

Deliverable R&D

Common Technical Document (CTD)

What is a Common Technical Document (CTD)?
The Common Technical Document (CTD) provides a shared format that is accepted by various regulatory bodies including the European Medicines Agency (EMA) in Europe, the Food and Drug Administration (FDA) in the United States, and the Ministry of Health, Labour and Welfare in Japan. It is mandatory to use this format for any new drug applications in Europe and Japan, and is recommended for new drug applications (NDAs) in the United States. This documentation is part of the application when registering a human pharmaceutical product. The guidelines for the CTD were developed under The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and is called the ICH M4 guidelines. The main purpose of the CTD is to provide a common format that reduces the time and resources to complete an application for registration across various jurisdictions. This also simplifies the communication between the applicant and regulatory bodies as the standard format is something that everyone involved is generally familiar with. One of the aims of the CTD is to allow for transparent and clear display of information. The ICH guidance specifies the type of paper it should be printed on, the font, font size, usage of acronyms, and more.

What are the sections of a CTD?
CTDs are divided into five main modules: 1-Administrative and prescribing information, 2-Overview and summary of modules 3 to 5, 3-Quality (pharmaceutical documentation), 4-Non-Clinical reports (Pharmacology/Toxicology), and 5-Clinical study reports (Clinical Trials). Module 1 is not always included in the CTD since the documents from the module are specific to each respective region. Module 2 contains 7 sections and gives an overview of the document with summaries. It introduces the drug stating its pharmacological class, proposed clinical use, and its mechanism of action. Next, it summarizes the quality of information and the Non-Clinical and Clinical overviews. These summaries reflect the information that is presented in the next modules.

Module 3 focuses on aspects including quality, manufacturing, chemistry, and controls reports. This section also includes information on the drug substance and drug product. Module 4 incorporates the non-clinical study reports. These sections are titled pharmacology, pharmacokinetics, and toxicology. This section takes a deep dive into the science behind the drug. Lastly there is Module 5, the clinical study reports. The reports of biopharmaceutic studies, studies pertinent to pharmacokinetics using human biomaterials, human pharmacokinetic studies, human pharmacodynamic studies, efficacy and safety studies, post-marketing experience, case report forms, and individual patient listings are all included in this module.

The use of CTD has significantly improved the application process but there are some discrepancies between countries. For example, the FDA requires submission of an Integrated Summary of Efficacy (ISE) and Integrated Summary of Safety (ISS) which was initially thought to be replaced by the Clinical Summary section of the CTD but persists as a separate requirement. Overall, this document positively impacted the regulatory review processes and created a simpler method of electronic submission. For the pharmaceutical industry, it no longer requires companies to reformat information in applications when submitting to different ICH regulatory authorities.

Who writes CTDs?
CTDs are generally written by medical writing groups in collaboration with broad cross-functional teams which hold expertise in specific elements contained within the document. Regulatory personnel will ensure it meets agency needs and aligns to broader regulatory strategy.

Medical R&D

Post hoc analysis

What is a Post Hoc Analysis?
A post hoc analysis is any analysis of a dataset that was not pre-specified prior to data collection. In pharma, it is most often used in the context of clinical trials and refers to analyses which were not specified in the original statistical analysis plan. Post hoc analyses may look at subgroups of interest or different endpoints than those in the primary analyses.

Post hoc analyses are often conducted following primary result communication and publication of clinical trials, especially pivotal studies. They can be a way of better understanding the trial results and population, although caution should be used given the higher potential for bias and cherry-picking once the broader results are known.

Functions R&D


What is Biostatistics?
Biostatistics is a specialization in statistics that focuses on application of statistical methods to studies within the realm of biology. In the context of pharma, biostatistics is a function which owns the statistical work associated with clinical trail design and analyses.

Specifically, biostatisticians in pharma can be part of clinical development teams and advise on things like proper sample sizes to ensure power, the types of statistical analyses which might be appropriate for the endpoints of interest, potential issues which may make statistical interpretation difficult and how to avoid them, etc. They help ensure that the clinical trials run by pharma and the associated statistical analysis plans are in line with broader statistical good practices.

Once data are collected, biostatistics also owns the actual execution of analyses per the statistical analysis plan. Biostatistics in pharma is often also charged with owning the post-hoc analysis work for presentation at congresses or publication as well as for potential uses for regulatory of health technology assessment purposes.