PROs and Data Collection

Site: EUPATI Open Classroom
Course: Documentation & Management
Book: PROs and Data Collection
Printed by: Guest user
Date: Thursday, 28 March 2024, 11:00 PM

1. Types of Data Capture

(This section is organised in the form of a book, please follow the blue arrows to navigate through the book or by following the navigation panel on the right side of the page.)

Data in a clinical trial are generated and collected by the investigator, the study staff or directly by patients (called patient-reported outcomes - PROs).

This can occur in the traditional way on paper or in electronic form:
  • CRF - Case Report Form - on paper including patient diaries or questionnaires.
  • eCRF - Case Report Form – electronic.
  • DDC - Direct Data Capture i.e. through electronic devices, data entered automatically into a database.
  • PRO - Patient-Reported Outcomes - patient questionnaires and diaries - on paper.
  • ePRO - Patient questionnaires and diaries – electronic via hand-held instruments like mobile phones or tablets.

2. Paper CRFs

Paper CRFs are designed for entering handwritten data. They are cheap to produce and allow the creation of direct copies through carbonless copy papers and faxing. Through new technology like optical character recognition (OCR) computers are able to ‘read’ the data written by the staff and to enter them automatically into a database.

Advantages

  • Low-tech - can be accessed anytime without a computer.
  • Easier to correct if problems are discovered during study conduct.
Disadvantages

  • Volume of paper to store during and after the study.
  • No automatic warnings concerning faulty data entry.
  • Additional step required to enter data into database (one more step where errors could be made).

3. Electronic CRFs


Electronic CRFs are increasingly popular but are much more complicated to produce and need to adhere to strict regulations in Europe and the US:
The computer systems and the eCRF software must be validated and it must be possible to see every correction that has been made to the data entered (audit trail). It must be ensured that only authorised persons have access to the programme and data. A back-up of the data has to happen regularly and automatically.

eCRFs in a study require that all investigator sites have sufficient and reliable access to computers and Internet. Intensive training of the site staff in using the eCRF is required, often also supported by a help-desk.

Advantages

  • The eCRF has automatic checks to reduce data entry errors and gives a warning if an error is made when entering the data (e.g. body temperature 370.6°C instead of 37.6°C). This also helps to avoid violation of protocol requirements.
  • The entered data is immediately available to the sponsor who can see whether the site has entered data correctly and when this took place.
  • Questions for further information on the entered data can be raised faster than in a paper-based system.
Disadvantages

  • Potential technical problems related to eCRFs or to the study site’s technical infrastructure.
  • Study staff may need specific training or be capable of using a particular electronic system.

3.1. Regulatory Requirements

The EMA issued a reflection paper in 2010 summarising what GCP inspectors will accept as electronic data capture. Read the complete document.
This document states, among many recommendations, that:

  • There must be criteria under which NCAs will consider electronic records and signatures to be trustworthy, reliable and generally equivalent to paper records and handwritten signatures executed on paper.
  • There must be a system validation to ensure accuracy, reliability, consistent intended performance (i.e. validation of the eCRF software), and the ability to discern invalid or altered records.
Likewise the FDA has issued very detailed and demanding rules under which conditions they accept electronic data capture. In a guidance for industry the FDA has explained how to use eCRFs in clinical trials. The Guidance for Industry recommends that:

  • The protocol should identify when a computerised system will be used to create, modify, maintain, archive, retrieve, or transmit data.
  • Documentation of software and hardware used should be kept with study records (in the Trial Master File (TMF)).
  • An electronic record is the source document if the original observation is entered directly into a computerised system.

4. Examples of Direct Data Capture (DDC)

Instruments that create data in a digital format are a usual source of information that gets directly linked to the study database. This sounds attractive but such connection must also follow strict rules and may be difficult to achieve. For example, when different laboratories are involved, they all have to adhere to the same data entry standards, normal ranges of their analytical methods, etc.

Some examples of direct data capture (DDC) are:
More recently, mobile apps can provide data by monitoring for example physical activity or quality of sleep.

5. Patient Reported Outcomes (PROs, ePROs)

The term PRO (patient reported outcome) is used for all data that is directly provided by patients. This includes all types of questionnaires and diaries either in paper or electronic form. If an electronic hand-held system such as a tablet or text messaging (SMS) are used, it is called ePRO. Typically this electronic data is either in a daily diary form in the patient’s hands, or questionnaires administered during site visits.

In our rapidly developing electronic world the technical tools that can be utilised to receive this data in an efficient, patient-friendly manner are constantly evolving.

Advantages of ePRO

  • Higher quality of data:
    • Automated edit checks ensure PRO data is often 100% clean – no need for extensive data cleaning.
    • Alarms and context-sensitive eDiary design achieves higher adherence to protocol.
  • Immediate intervention possible when problems or deviations occur.
  • Allows clinicians to concentrate on treating their patients - and spend less time on data entry.

Disadvantages of ePRO

  • Greater technical effort and therefore more expensive than paper.
  • Not all patients are familiar with modern technology.
  • Like every electronic instrument there can be failures and break-downs.
  • More time required for the site staff to explain the use of the system to the patient.
  • Access to the internet needs to be available.