How Does an eCRF Help to Achieve High-Quality Data in a Clinical Trial?

How Does an eCRF Help to Achieve High-Quality Data in a Clinical Trial?

How Does an eCRF Help to Achieve High-Quality Data in a Clinical Trial

If you need an electronic CRF software, you can contact us at info@klindat.com

In clinical trials, patient data is everything.

The final product of a clinical trial is a set of data files that include all the research results, which, in the end, will be what regulatory agencies evaluate to decide whether a new drug is approved or not for market commercialization.

In other words, after all the resources and efforts invested in a clinical trial —which are not few— what really matters is to conclude the research with reliable and high-quality data.

That said, an obvious question is: How can high-quality data be obtained in clinical trials?

Certainly, there are several factors that have a direct impact on the reliability and quality of the information generated in a clinical study.

However, in this article we are going to focus on those aspects specifically related to the collection and cleaning of patients’ clinical data using an eCRF.

Ultimately, we will learn how an electronic CRF can help to achieve high-quality data in a clinical trial.

Why Is It Important to Collect High-Quality Data in Clinical Trials?

As already mentioned, data are the most valuable asset of a clinical trial, that is, the results that will make it possible to authorize a new drug.

It is important to note that a clinical trial generates an enormous amount of information and different types of data and documents of different nature.

The following are some examples of data and documents derived from a clinical trial:

  • Regulatory and ethics committee documents (applications and approvals to conduct the study)
  • Financial documents (budgets, invoices)
  • Legal documents (contracts)
  • Technical and scientific documents (clinical study protocol, drug product sheets, CRF specifications)
  • Clinical data (information entered in a case report form by the participating hospitals)

These are just a few examples of the documentation and information that is involved in a trial.

All these data and documents are important for the success of the research, but special attention should be paid to the patients’ clinical data that have been entered into the study database (case report form).

Although all the other documents mentioned above are fundamental, the “heart” of a clinical trial is the clinical data of the patients who have been treated with experimental drugs.

More specifically, patient safety and efficacy data are the information that regulatory authorities, such as the Food and Drug Administration (FDA) or the European Medicines Agency (EMA), will ultimately evaluate to decide whether a new medicine should be approved or not.

In simple words, safety and efficacy data from a clinical trial hold the key to the success of a pharmaceutical development program.

With this understanding, we can realize the importance of clinical trial data, and why they must be of the highest quality.

What Data Are Collected in Clinical Trials?

Different types of data are collected in clinical trials. Below is a list of the most common data, using a clinical trial in oncology as an example:

  • Patient information and informed consent form
  • Tumor diagnosis forms
  • Patient eligibility confirmation sheet
  • Patient inclusion
  • Demographics and medical history
  • ECOG status
  • Biochemistry
  • Hematology
  • Coagulation test
  • Serologies
  • Pregnancy test
  • Height and weight
  • Physical examination
  • Vital signs
  • Adverse events
  • Concomitant medications
  • Electrocardiograms
  • Ejection fraction
  • Carbon monoxide diffusing capacity
  • Peptide testing
  • MRI and CT scans
  • Quality of life forms
  • Biological sample collection forms
  • Dosage of medications
  • Survival follow-up

How Are Data Collected in Clinical Trials?

Nowadays, the most common method of collecting patient data in clinical trials involves the use of an electronic Case Report Form (eCRF).

An eCRF system can be defined as a software used to collect, store, clean, and transfer data in a clinical trial.

In essence, investigator teams from hospitals participating in a trial have usernames and passwords to access the eCRF through the Internet, and in this way clinical information is entered into the various forms that make up the eCRF.

The data entered by the hospitals is then reviewed by specialized data managers, who are dedicated to verifying that all the information is complete and consistent. 

Once the clinical data have been fully cleaned, they are exported into files that are later used for statistical analyses and, finally, scientific publications.

How Can the Quality of the Data Collected in a Clinical Trial Be Improved?

There are several tasks that need to be performed to guarantee high quality of the data collected in a clinical trial.

These tasks aim to ensure the integrity, reliability, and consistency of the clinical information, so that the results accurately reflect the reality of the research that has been conducted.

It is vital to understand that the work of managing data in a clinical trial starts at a very early stage before the clinical trial actually begins.

In the following lines, we summarize the most relevant elements that will contribute to achieving refined and error-free clinical data. 

Protocol design

When it comes to data quality, it all starts with the design of the clinical trial protocol.

The trial protocol is a key document that contains the scientific background and specifications of the objectives, procedures, and tests of the clinical trial, among many other things.

In particular, the trial protocol includes a table of procedures and tests to be carried out in the different visits that the patient will make to the hospital, while receiving the trial treatment and in the subsequent follow-up.

This table is crucial for specifying clinical trial forms and data. Put it differently, the study’s procedures, tests, and visits —embodied in the protocol— determine what data will be collected and when.

Obviously, if the protocol design —which includes the specification of the table of procedures and tests— is incomplete or inaccurate, these deficiencies will carry over into the study and create problems at subsequent stages.

To put it bluntly, if the visit and test specifications are wrong, the data collection forms included in the eCRF will also be wrong.

It is not uncommon that an oversight or error in the specification of tests in a clinical trial impacts the subsequent data analyses. For example, if a particular test was not initially specified in the protocol —and therefore not in the eCRF— that information will not be available at the time of analysis. Unfortunately, it can be very costly to have to go back and reclaim these data once the study has been underway for some time.

Therefore, it is essential that not only the sponsor of the clinical trial, but also the coordinating investigators, and all the parties involved in the project, deeply examine the design of the visit table in which the investigation procedures are specified to avoid future inconveniences.

eCRF specification

Once the protocol contains a complete and accurate table of tests and procedures, the design of the eCRF system can be specified.

Using this table as a reference —along with the relevant comments and annotations in the protocol— the eCRF specifiers can begin the design of the electronic CRF.

The eCRF design must be faithful to the visit structure of the protocol and should contain forms that include the necessary data related to each of the procedures and tests.

The protocol may not specify all the details of each of the data to be collected in the electronic case report form; hence, the eCRF design team should verify with the coordinating investigators —who are the clinical experts— if the eCRF forms that have been specified include all the information to be collected.

In summary, the objective of this step is to produce a highly accurate eCRF specification that does not leave out any important data.

eCRF implementation, testing and validation

When the eCRF specification documents are ready, it is time to convert the eCRF specification into actual forms using the eCRF software.

Data managers from the clinical trial sponsor or the company in charge of building the eCRF —often a Clinical Research Organization, or CRO— will be responsible for transforming the eCRF specification into the web forms that will be filled out by users in the study hospitals.

Implementing the forms into the software is a task followed by an additional step of testing that the eCRF software that has been built works flawlessly.

To verify that the eCRF system works correctly according to the required specifications, the data managers in charge of implementing the tool will perform and document tests that will provide evidence that the software has been tested and validated.

Without a doubt, the construction, testing, and validation of the eCRF are vital elements to ensure high-quality data in a clinical trial.

Development of a data validation plan for each specific study

An important next step in the clinical trial information management process is the development of the data validation plan.

The purpose of this document is to specify which conditions the data entered into the electronic CRF must meet —for each specific study— in order to be considered complete and suitable for analysis.

When the participating hospitals enter the data into the eCRF, the information frequently contains inconsistencies that will need to be resolved through queries (requests for rectification or clarification sent to the sites).

This means that the data will have to be cleaned until the validity and accuracy requirements that have been defined in the validation plan are met.

In other words, data cannot be analyzed until they are fully complete and free of discrepancies.

Training of research teams and data entry managers

Another factor related to the quality of the data collected in an electronic case report form is the training of the people who are responsible for data entry, that is, the research teams and data entry managers in the hospitals.

Effective training of the teams entering the data into the eCRF will help to ensure timely and error-free completion of the forms.

A better understanding of the data to be entered will help hospital staff and reduce the number of queries needed to resolve discrepancies.

Entering data from an early stage

Continuing with the responsibility of those in charge of entering the data in the participating sites, the relevance of entering data from an early stage, without delays, as soon as information on tests and procedures is available, should be highlighted.

Sometimes there are substantial delays in data entry into eCRFs. Whether due to low staff availability, technical problems, or another factor, it is common for a center participating in a clinical trial to accumulate significant delays that can even affect the scheduled time to analyze the data.

If the investigator teams can enter the information into the eCRF quickly, the entire process of reviewing and analyzing the data will be streamlined.

Verification of source data by monitors

One of the most relevant tasks with a direct impact on the quality of the data collected in an eCRF is undoubtedly source data verification.

Source data verification consists of comparing the information entered in the eCRF fields with the information as it appears in the original documents (medical records located in the hospitals).

This task involves onsite visits to the hospital and is performed by a Clinical Research Associate (CRA) —also called a monitor— and is certainly a crucial element to guarantee that the data provided by hospitals are real and reliable.

Therefore, a good monitoring plan —and its correct execution— will contribute significantly to improving the overall quality of a trial’s clinical data.

Thorough review and execution of queries by data managers

As mentioned above, in a clinical trial, queries are issued to participating sites to resolve inconsistencies as well as clarify doubts about the data entered into the eCRF.

In part, the monitors in charge of doing the source data verification will issue queries as they review the information in the medical records during their monitoring visits.

Nonetheless, there is another team dedicated to reviewing the quality and consistency of the eCRF data, which is made up of data managers assigned by the study sponsor.

These data managers may be the sponsor’s own employees, or they may belong to the biometrics department of an external outsourced CRO.

Data managers carry out a comprehensive review of the data that have been entered into the eCRF using advanced data processing tools that facilitate their review, even when handling large volumes of information.

Through their reviews, data managers will detect discrepancies that will be sent to the research teams at the sites for prompt resolution prior to analysis.

How Does an Electronic CRF Help to Obtain More Reliable Data?

After understanding the elements necessary to ensure high-quality data from a clinical trial, it is worth digging a little deeper into how the use of an electronic CRF will help to achieve more reliable data.

In the following lines, we summarize the mechanisms that eCRFs should have in order to preserve the integrity and improve the accuracy of the clinical trial’s data:

  • Accuracy: A well-designed eCRF will collect only the data needed for a given study. Additionally, it will use different types of fields —such as drop-down menus— with pre-defined values that will reduce the chances of error (avoiding free-text fields). 
  • Security: eCRFs integrate various security mechanisms that preserve the integrity of the recorded information. For instance, they include access control methods that protect against intruder attacks and backup systems to recover data in case of serious incidents.
  • Traceability: An essential module of a good eCRF is the audit trail, which is a module that records all activity that takes place on the eCRF platform, including a record of inclusions and modifications of clinical data. This allows to monitor the activity of all users in the eCRF and to reconstruct —if necessary— any events of interest that have occurred.
  • Monitoring: eCRFs integrate buttons that allow marking the fields on which source data verification has been performed. This greatly facilitates the work of monitors as they review patient information in the hospital.
  • Query management: Electronic CRFs have considerably improved the way queries are issued and resolved in clinical trials. Both monitors and data managers can manage queries quickly through specific buttons and listings integrated into the eCRF itself, while site personnel can easily resolve these queries using the same eCRF environment.

Conclusion

Data from patients who have received investigational drugs are the cornerstone of a clinical trial.

This information will be evaluated by regulatory agencies to authorize a new medicine.

Therefore, it is extremely important to collect and clean the clinical data of a trial with the highest quality assurance.

An eCRF improves the accuracy, security, and traceability of clinical data. At the same time, it facilitates and speeds up source data verification as well as query resolution.

To sum up, the use of a good electronic CRF —in the hands of an expert data management team— will contribute to achieving successful data management and data cleaning, and is therefore one of the keys to the success of a clinical trial.

If you need an electronic CRF software, you can contact us at info@klindat.com

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