Case Report Form (CRF) : Design and Development

ICRI

Overview

• Importance of collecting good quality data via paper CRF and eCRF

• Elements of good form design

Good Clinical Practice

Two main aims of GCP:

• Assurance that the data and results of the trial are accurate

• Assurance that the rights, integrity and confidentiality of trial subjects are protected

Case Report Forms (CRFs)

• Instruments used to collect data from clinical trials

• Designed to collect data points specified in the protocol

• Paper or electronic, even though electronic is becoming more common, paper still widely used

• Designed to help keep visit schedule and data collection in sync

Importance of well designed CRF

• Ensures consistency across patients

• Clear and easy for investigator

• Efficient for data management processing

• Appropriate, consistent, reliable and clean data for analysis

• Aids computerization of data

Form Design Principles(The 3 C’s)

• Clear

• Concise

• Consistent

Form Design Process

• define data items and timepoints

• draft

• pilot

• finalise questions

What to collect?    Primary safety and efficacy endpoints

demography (refer annexure 1) inclusion and exclusion criteria (refer

annexure 2) medical history (refer annexure 3) test article dosing information concomitant medicines (refer annexure 4)concomitant non –pharmacologic treatments adverse events (refer annexure 5) study termination and test article withdrawal

(refer annexure 6) lab data (Hematology, Biochemistry)

Points to be kept in mind!

• Avoid duplicate data

• Collect raw data, rather than calculated data

• Avoid ambiguity

• Avoid long comments

• Diagrams and analog scales

• Log type forms for AEs, etc.

• Sections or modules crossing pages

Consistency of question format of question format• Which format to use?

Circling yes no

Underlining yes no

Deleting yes no

Tick boxes yes no

Choosing a code yes =1 no=2 Answer = 1

Consistency of question layout

• Age group

18-25 26-35 36-45

• Age group

18-25 26-35 36-45

Clarity of questions

• Avoid double negatives

eg. The patient is not taking statins? Yes/ No

Is the patient taking statins? Yes / No

• Keep answers ‘positive’

eg. Are you in worse health than a year ago?

Are you in better health than a year ago?

Response control

• Format boxes to force desired response

Shade boxes

e.g. Is the patient eligible? Yes No

Give units

e.g. Date mm/dd/yy

Haemoglobin g/dl

Type of responses

Open: text, number,alpha numericClosed: check box, multiple choiceCombination: open and close

Open Responses  Free texts: avoid if possible, (can’t

analyze this data), limit length, use when needed, for example, AE text, medication text, medical history

 Date/time: specify format on CRF, helps to have character separators or boxes

 Number responses should have character separators with decimals to indicate precision

Closed Responses

• Provides a list of options, Yes/No, checkbox is clearer/cleaner choice

• Consistent coding across CRFs, use same order and number for same responses, i.e., ‘Yes’ is always 1, ‘No’ is always 2

Combination Responses

• Used for Other selection of a coded response to specify in text, i.e., If abnormal, specify

• This information can be used for future studies, if you want to determine additional options to be used

The Essentials• Study name/Identifier• Unique subject identifier• Form name (& number)• Page number• Patient identifier(s)• Signature of person completing form • Date form completed• Instructions (when to complete, where to

send)• Items need to be numbered for easy

reference

What to consider: Impact on design • Develop CRFs that follow the flow of

study procedures• Group the same type of data together

on the same forms• Should make sense to the person

completing the CRF• How/when is the CRF completed?• CRFs for data from charts across visits,

collected at end, can be a logging format

What to consider: Impact on design

• CRFs spanning visits, i.e., current medications, be sure to provide check box at each visit as reminder for updating

• CRFs completed by clinic staff during each visit, need to be replicated, with each visit, clearly marked (i.e., Baseline, Visit 1, etc.)

• If patient is completing CRF, need to consider patient population, education level, culture, etc.

What to consider: Impact on design

    Referential Questions: where the answer will determine what to complete (increase potential errors in data and completion), i.e.,

   If the answer to #3 is No, go to question #10

   If the answer to #2 is AE, complete Form 15

What to consider: layout and organization

 Identifiers in header with most often referred to information in upper portion, easy to access

  Margins sufficient so binding, hole punching, copying does not interfere with text or body of CRF

  Font style change for headers, using bolding or italicized for instructions help the form filler identify specific sections and complete CRF

  Font size should be easily readable, copy and fax well

  Units should follow text response to guide the form filler

What to include in CRF Package? CRF Completion Guidelines (developed

in collaboration):

General instructions: Use of permanent ink on CRFsAll items are completeList of abbreviationsContact informationProcedure for making corrections on CRFProcedure for visits of CRFs that are not

done

What to include in CRF Package?

Specific page-by-page instructions:Procedure for visits/exams/tests not doneProcedure for withdrawal/stopping

completionInstructions for Adverse Events and SAEs

What to include in CRF Package? 

 CRF Study schedule (time and events)

 Checklist and section dividers, by visit

 Extra CRFs to be used for unscheduled visits

 On-line URL: (if available) for reference and FAQs that are updated during life of study

Other considerations• colour / shading

• carbon copies

• single sheets vs booklets

• guidelines on form completion