Objectives

Patient-Reported Outcomes (PROs) are widely used in clinical studies to assess treatment benefits for patients. Currently, there is increased interest in examining the wording and types of PROs contained within approved product labels. Information about these medical products is widely available on regulatory agencies' websites. However, there is no single website that summarizes all the evidence about PRO claims in the labeling of medical products for disease areas, conditions, and manufacturers.

In order to bridge this gap and provide easy access to this information, Mapi Research Trust, in collaboration with Mapi Values has created the PROLabels database.

PRO definition

According to the EMEA (CHMP, 2005)¹: "Any outcome based on a patient’s perception of a disease and its treatment(s) scored by the patient himself is called a Patient-Reported Outcome (PRO). PROs are a large set of patient-assessed measures ranging from single item (e.g., pain VAS, overall treatment evaluation, and clinical global improvement) to multi-item tools. Multi-item tools can be mono-dimensional (e.g., measuring a single dimension such as physical functioning, fatigue, and sexual function) or multi-dimensional questionnaires measuring several of the following: symptoms, functional status, satisfaction, well-being, or health-related quality of life (HRQL). In general terms, PROs provide information on the patient’s perspective of a disease and its treatment."

The FDA suggests the following definition²: "Any report coming directly from patients (i.e., study subjects) about a health condition and its treatment."

By definition, medical products for which there is evidence of physician-reported outcomes in labeling are not included in this database. However, we included proxy- and caregiver-reported outcomes, especially in the cases of psychoses, dementia and pediatric studies.

1 CHMP: COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE. Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medicinal products. 2005. Available here.

2 U.S. FOOD AND DRUG ADMINISTRATION. Guidance for Industry. Patient-Reported Outcome measures : use in medical product development to support labeling claims. Draft guidance. 2006. Available here.

Information sources

We review the information on human medical products published on the websites of the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). If a marketing authorization is withdrawn or discontinued, the corresponding product in the PROLabels database will be displayed with an orange background.

The process used to develop the database involves examining each drug authorization report published on the FDA and EMEA websites and extracting valuable information about the medical products for which a PRO claim was granted in the label.

• EMEA data : On its website, the EMEA publishes reports for all the drugs approved since a centralized procedure was established in 1995. We examine the European Public Assessment Reports (EPARs) of all approved drug products, with special attention to the Summary of Product Characteristics (SPC). To complete our records, we search for clinical studies which included Patient-Reported Outcomes (PROs) endpoints (whether primary or not) and, when necessary, retrieve additional information in Scientific Discussion documents.
  
  
• FDA data : On its website, the FDA's Center for Drug Evaluation and Research (CDER) publishes reports for all drugs approved in the United States since 1998. We examine all product labels of New Molecular Entities (NMEs). We retrieve additional information in the Medical Review when necessary. In addition, we have undertaken a large development plan to include, from 2008 on, all New Drug and Biological Approvals (i.e. NMEs, BLAs, revisions, efficacy supplements) in the database as soon as they are published on the FDA website. We have also started a retroactive review from 2007 and working backwards.

In summary, the primary source of information on the PROLabels database is the Clinical Studies section of the Summary of Product Characteristics (SPC) for the EMEA (mainly from section 5.1.) and/or the product label for the FDA. We only consider efficacy studies and not safety studies.

Information analysis

Once we identify the evidence of a PRO labeling claim, we include the corresponding medical product in the PROLabels database. We then complete the record by gathering the following information in five sections:

• Clinical study details
• Claim: the PRO claim itself, as mentioned in the source document. When the results are only presented as numerical data, we include a copy of the table from the primary document.
• Design: summary of study characteristics e.g., number of patients, treatment arms, duration, etc.
• Study endpoints : the primary endpoint(s) of the study, the PRO endpoint(s) which are reported in the label and the additional PRO endpoint(s) that are not reported in the label. This section also reports the definition of the response when available in the primary documents.
• PRO information: which PRO is assessed, how is the PRO evaluated and, in case a PRO instrument is used, a brief description of the instrument with links to additional information sources.


• Pharmacological action details
• Anatomical Therapeutic Chemical (ATC) Code of the drug: this classification, provided by the WHO (World Health Organization), divides drugs into different groups according to the organ or system on which they act and their chemical, pharmacological, and therapeutic properties.
• Mechanism of action.
• Therapeutic area: this comes from the MeSH (Medical Subject Heading) classification of diseases, provided by the U.S. National Library of Medicine.
  Please note that a drug may be classified under more than one therapeutic area.
• Therapeutic indication (general): this is the MeSH term equivalent to the term used in the source document.
• Therapeutic indication (specific) as stated by the sponsor in the indication section.
  
  
• Application details
  
This section gathers all practical information about the application:
• Source of the data and approval identification number(s).
• Marketing Authorization Holder: name and location.
• Date of approval and, when relevant, the date of last available revision.
• FDA Division
• Involvement of the Study Endpoints And Labeling Development group (SEALD)
  
  
• Information sources
• Regulatory documents : links to the authorization reports (i.e. product label, SPC) on our website and on the regulatory agency website. This document can be viewed in PDF format (Portable Document Format).
• Bibliographic reference(s): if present in the primary source
  
  
• Selected bibliographic references
  
Same or different clinical study involving the drug of interest in the same therapeutic indication where PROs have been used, and retrieved from Medline

Database content and search options

We review all drug marketing authorizations available on the EMEA website since 1995 and on the FDA website for New Molecular Entities (NMEs) since 1998. After logging in on the PROLabels home page, you will go directly to a table that lists the medical products within the database under these headings:

• International Non-proprietary Name (INN)
• Brand name
• Marketing authorization holder
• Therapeutic area(s)
• Therapeutic indication(s)
• PRO (reported in label)
• Date of approval
• Regulatory agency
• FDA Division

The medical products list is automatically sorted by INN in order to display – on two consecutive rows – a product authorized by different regulatory agencies. However, any column may be selected to sort the data by simply clicking on the top of that column.

You will also find a search form on this page that will enable you to search the entire database. This simple search engine retrieves results based on the exact wording of the phrase you type in. Advanced search options are also available to perform queries on up to ten criteria and even combine queries with the usual AND, OR, and NOT operators.

On the "subscriber-only" part of the database, the content is further subdivided by information source, year of approval, therapeutic area, and PRO instrument used in the clinical studies. You can find the previous month's additions listed on a separate page, for a quick update on recent changes made to the database.

A click on a line of the table, in the 'Details' column, opens the results page which contains the full record organized as described below.

Results display

The full record for a given medical product / regulatory agency is displayed in a separate page featuring different headings, as described above in the information analysis section:

• Therapeutic indication
• Clinical studies details
• Pharmacological action details
  
  
• Application details
  
  
• Information sources
  
  
• Selected bibliographic reference(s)

As an example, here is the page on Taxotere, an antineoplastic drug for which a PRO claim was granted by the EMEA in 1995.

 

 

 

Database update

The PROLabels database is updated once a week, in order to give you the latest comprehensive information on medical products. This update includes new marketing authorizations published on the FDA and EMEA websites, as well as variations of already approved products.

Quality check

The definition of the inclusion criteria was performed by Marie-Pierre Emery, MSc (Director of the Information Resources Centre of Mapi Research Trust) and Catherine Acquadro, MD (member of the Mapi Research Trust Scientific Advisory Committee (SAC) and the Scientific Advisor to this project), with the collective support of the following members of the SAC:

• Dick Joyce, PhD
• Donald L. Patrick, PhD, MSPH
• John Ware, Jr, PhD
• Albert Wu, MD, MPH

A quality check of the database is performed on a regular basis.

Future developments

Currently, PROLabels is based on information from the FDA and EMEA websites, but data from other regulatory agencies will be included.

We welcome your suggestions and comments, so that the PROLabels database will better suit your needs. Contact Us.