Our society is witnessing an unprecedented age characterized by the growing threat of an increasing number of health risks and life-threatening diseases.
For example, prevention of cancer has become one of the greatest public health challenges of this century. The effects of globalization, new lifestyles, contamination, and population aging, which especially characterize developed countries, have had a profound impact on our overall health: all these factors contribute to increasing the probability of becoming sick.
Cancer is a serious medical condition affecting more and more people every year. This is evidenced by the fact that, according to the Cancer Research UK website, there were an estimated 17 million cancer cases around the world in 2018, while 18.1 million people received a new diagnosis of cancer worldwide in 2020. Additionally, the number of new cases is expected to increase up to 27.5 million by 2040. [1]
In the current global scenario, health organizations and authorities, both national and international, are trying to promote healthier lifestyles to address this threat. For example, they encourage people to change dietary patterns, increase physical activity, and reduce tobacco and alcohol consumption, among other preventive measures.
Another clear example of a global health challenge is the irruption of the COVID-19 pandemic, which has affected the life of society as a whole, as we all know.
As a result of the above realities, recent years have witnessed a boom in research and development of new drugs and therapies to combat challenging diseases. In turn, this situation has led to the emergence of new technological solutions for clinical trial management, and in particular for clinical data collection, such as electronic patient-reported outcomes (ePRO) systems and electronic case report forms (eCRFs).
Zlynger is a technological provider with a long track record in clinical research. We have been offering, for more than ten years, software solutions and data management services to many biotech and pharma companies, academic research groups, university hospitals, and independent investigators across the United States, Europe, and beyond.
We deliver eCRF solutions to customers as part of our software suite offer for managing clinical trial data. In this article, we will provide a brief overview of what an eCRF is and delve into the main advantages associated with this advanced software technology for clinical research.
What Is an eCRF in Clinical Research and What Are Its Advantages Over a Paper CRF?
The term eCRF is an acronym for electronic Case Report Form. Based on a study published on the National Library of Medicine, the International Conference on Harmonization (ICH) Guidelines for Good Clinical Practice (GCP) defines an eCRF as “a printed, optical or electronic document designed to record all of the protocol —required information to be reported to the sponsor on each trial subject”. [2]
Simply put, an eCRF is a web-based software application used to collect data of clinical study participants. This electronic tool has proven to be paramount to the success of a clinical trial as it enables the quick collection of valid and consistent information and, consequently, simplifies and accelerates data analysis.
The use of an eCRF guarantees that all relevant data gathered from the patients enrolled in a study, as well as the forms in which hospital personnel insert clinical data, are accurate and complete. These data may relate to demographics, medical history, blood tests, vital signs, treatment information, adverse events, and other relevant information regarding the patient’s health condition.
In the era of digital transformation, electronic case report forms (eCRFs) are being growingly employed for data capture in clinical research. However, paper-based data capture (pCRF) is still largely used in clinical trials. Data recorded on paper CRFs are entered into the clinical database by staff members at the sponsor or the Clinical Research Organization (CRO).
Generally, paper-based CRFs have been deemed more suitable when studies are small, while electronic CRFs are considered a better option when clinical trials are larger. Be that as it may, paper CRFs will, in all likelihood, be entirely replaced by the digital form of data collection.
Actually, filling out patient information on paper forms is a time-consuming and environmentally unfriendly activity which can lead to many security and quality risks. In fact, manual data handling is far from being the most accurate way of capturing clinical data as it can certainly result in many errors, loss of information, inconsistencies, and even fraud.
In light of the above, an increasing number of research organizations and biotech companies are implementing eCRFs to support clinical trials. Software vendors are constantly improving these advanced technologies and including new functional enhancements, features, and approaches to keep up with changes in the industry.
All these modifications are implemented taking into account the characteristics of the studies as well as the needs of the end-user, that is, the professional who will enter the data into the eCRF. Furthermore, the processes involved in the preparation are usually subject to the guidelines contained in the corresponding Standard Operating Procedure (SOP) to guarantee that best practices of eCRF designing are followed.
Beyond doubt, eCRFs have had a very positive impact on the clinical data management paradigm. They have become the mainstream in clinical research due to their numerous advantages over traditional paper-based CRFs. For instance, these web-based tools can speed up data capture time, deliver the highest quality data, facilitate robust analysis, enable the widest possible integration, reduce query generations, and ensure improved data accuracy and integrity.
Many clinical research specialists can benefit from implementing an eCRF. Indeed, the design of an eCRF is usually standardized to meet the needs of all its users, including investigators, clinical data managers, study monitors, biostatisticians, data entry personnel, database developers/programmers, and other clinical trial stakeholders.
To date, an eCRF is the most powerful strategy for a systematic, reliable collection of clinical trial data. Capturing data electronically makes the process of collecting and storing information in the central database of the clinical trial much faster and more efficient.
How Can an eCRF Maximize the Efficiency and Productivity of a Clinical Trial?
As we have already seen, the role of an eCRF is essential as it optimizes data management activities (e.g., data cleaning, validation, and extraction) and ensures the quality, simplicity, control, and traceability of all the data collected in a study.
In this section, we will examine the most significant advantages of implementing an eCRF for clinical investigation.
The importance of a decisive commitment to eCRF training
First of all, in order to guarantee that proper use is made of an eCRF, the site staff must receive intensive training to be able to use this electronic system. It is therefore necessary to provide them with all the devices and resources required, including reliable access to computers and the Internet.
In addition, study staff should also be given clear and detailed instructions to avoid any problems arising from a poor understanding of its functioning. On the other hand, keeping in mind that technical problems may always occur, ensuring the support of a help-desk is vital too.
Evidently, both training the staff in charge of data collection and management, and having a help-desk available to assist eCRF users with their problems will come at a cost. Nonetheless, one of the main pillars of success in clinical research lies on placing stress on the training of all the personnel.
Hence, allocating sufficient funds to develop the appropriate expertise and skills in the field of electronic data capture software is a worthwhile investment that, in the long run, will help sponsors maximize productivity and efficiency, as well as attain their goals for clinical trial management.
An easy-to-use software application
Despite the foregoing, an effective eCRF design will always be user friendly. Ideally, an eCRF will be well-structured and easy to complete. It should capture valid, consistent, and legible data, thereby enhancing data flow and reducing query generations.
With the purpose of improving the quality of the data collected, design standards should be adhered to when designing an eCRF. Moreover, this software application should aim to facilitate data analysis and make it simplified.
Full compatibility with multiple browsers, systems, and devices
Modern eCRFs are, in general, entirely compatible with all the latest versions of the most widely-used web browsers (e.g. Google Chrome, Mozilla Firefox, Opera, Safari). They also allow for interoperability with various devices —such as desktop computers, smartphones, tablets, and medical devices— and enable the export of clinical data in different formats (Excel, CSV, SPSS, XML) with a single click.
These innovative tools can also connect with ePRO apps, which are mobile applications that allow patients to actively participate in the clinical trial by submitting self-generated information.
Likewise, eCRFs can also work in conjunction with Randomization and Trial Supply Management (RTSM) systems. These technologies are employed by clinical trial site managers to randomize patients as well as to manage drug supplies for a clinical research study.
Additionally, an eCRF can also be used to import data from external sources. For instance, this tool enables investigators to import information such as laboratory findings or data generated by radiology reviewers, the latter being particularly common in clinical trials in oncology.
A convenient software with time-saving features
Using an eCRF not only streamlines clinical and data workflows, but also saves valuable time. As an illustration, it allows for fast study build by offering digital templates that can be easily tailored to the specific needs of each new study.
Nevertheless, the main factor contributing to this considerable saving in time is the elimination of the data entry step that is part of the paper CRF data collection process. Albeit well-established, transcribing the data on paper is a time-consuming and error-prone task.
For this reason, it is highly convenient to replace the paper-based method by electronic records. By doing so, the information will be entered directly into the database, which means that the trial sponsor will be given quicker access to the data ready for validation.
Certainly, an eCRF is a very practical tool that can substantially reduce the time needed to collect and manage clinical data. In effect, it will improve the query response time, enable remote data review, and shorten the time required to review data. In this way, most of the data cleaning activities will be done during the completion of the eCRF, ultimately resulting in less time and effort required by the data management staff.
Thanks to this ease of administration and gain of time, sponsors and biopharmaceutical companies can conduct large multicenter studies simultaneously. Moreover, eCRFs are also designed taking into consideration the global dimension that increasingly characterizes the clinical research market today. Therefore, these cutting-edge software tools can help investigators capture and manage clinical data from multiple studies and across different countries at the same time.
All things considered, implementing an eCRF to support a clinical trial will help clinical research centers and CROs obtain clean data more quickly, which will result in faster regulatory submission and approval. Moreover, by virtue of the automation of this very practical tool, sponsors will achieve the speed and operational efficiency that the current clinical trial market demands.
Incorporation of pre-coded answers to get accurate data
When it comes to collecting data, the adoption of simplicity and user-friendliness should be considered to obtain accurate and relevant data for a clinical trial. For example, when designing an eCRF, it is advisable to use a plain language that can be easily understood by all participants, divide the information in an organized way, avoid ambiguity or much text on a given page, among other linguistic, textual, and structural aspects.
In contrast to the paper-based method, the layout design of an eCRF does not depend upon printing costs. This gives you the freedom to use medium or large fonts on it. In addition, incorporating standard data formats (e.g. dd/mm/yyyy), clear guidance about skip patterns, and required fields on the electronic form can also be effective to collect the most critical data, which will help to increase the eCRF’s success rate.
The adoption of measurable answers, wherever possible, will also prevent errors in the filling out process. Examples of pre-coded answer sets include yes/no, mild/moderate/severe when describing the severity of adverse events (AEs), or ratings from 1 to 10 when referring to pain levels. Consistency in codes will certainly facilitate data entry at the eCRF and simplify data interpretation and analysis as well.
Another essential ingredient would be related to the collection of quantifiable data. While quantitative data has to do with numbers and countable or measurable information, qualitative data often contains descriptions and opinions that can lead to different assumptions and interpretations about the clinical data.
Bearing this in mind, free text responses should be minimized to the extent possible to avoid distortion of information in interpretation. Not only that, but it is crucial to provide adequate explanation adjacent to the eCRF fields to ensure clarity and uniformity among raters. In sum, quantitative data should always prevail over qualitative data.
Improved data cleaning and quality of clinical study management
Data cleaning plays a decisive role in clinical trial success. In effect, the entire clinical trial may be adversely affected if the information collected is poor or incorrect as it may result in misleading conclusions, or less accurate findings, regarding the safety and effectiveness of the treatments that are going to be released onto the market.
An eCRF will improve data accuracy by significantly decreasing the number of errors made during the data entry process. These electronic tools have been designed to accelerate data collection and reduce the risks and mistakes arising from manual data handling, such as data loss or duplication of information.
For instance, computerized systems contribute to cleaner data by enabling legible entries, automatic calculations, consistency checks, and better data management quality performance. The system will also generate unvarying and repetitive data (e.g., subject ID, patient initials, site code, or protocol ID) automatically, thus avoiding redundant data or duplication of eCRF pages.
However, despite the great reliability and robustness of an eCRF, occasional errors, discrepancies, or inconsistencies may still occur during the process of clinical data collection. If any incorrect entries are identified by the automatic detection mechanisms, the teams in charge of reviewing and managing the data captured will prepare and send queries to the hospitals so that these inaccuracies can be revised and rectified by the study coordinators.
Certainly, an eCRF allows clinical researchers to make the necessary changes to speed up the cleaning process in an efficient and comfortable manner. Only will the data be considered ready for analysis once all the information collected has been checked and confirmed to be completely accurate and complete.
Automation and digitalization contribute largely to cleaner data entry and improved quality of clinical study management. By dint of the edit checks and systematic approach of an eCRF, all the processes related to data collection and cleaning will be reduced, which will help to speed up the clinical trial.
In short, an eCRF is a very practical tool for improving and accelerating data entry, reviews, and cleaning. The collection of high-quality data not only will avoid violation of protocol requirements, but it will also be translated into better interpretation and analysis of the results. Ultimately, computerized collection and management of clinical data will give investigators and study sponsors more time to focus on the most important tasks of the actual research.
Enhanced data protection and security
When it comes to recording and handling sensitive data from clinical trials, the adoption of privacy and security measures ought to be the main priority. Adhering to international data security laws, principles, and quality standards (e.g., Clinical Trials Regulation (EU), GDPR, or GCP guidelines) also proves essential to harmonize clinical trials, as well as to ensure patient safety and the maximum transparency of the data captured.
Data protection authorities also play an important role as they are in charge of informing data processors and controllers of their responsibilities when dealing with confidential information. In addition, they strive to raise the general public’s awareness of the risks, safeguards, and rights related to data processing.
The digital collection of clinical research information poses new risks and challenges to data safety, especially due to the fact that more people —such as monitors or data management staff— can have access to the data. Notwithstanding this potential threat, modern eCRFs have robust protection measures, approaches, and advanced mechanisms to guarantee an optimal level of data security.
As a matter of fact, eCRFs allow for much more secure access and storage systems than printed CRFs. More specifically, these applications have built-in security features with respect to user authentication and data encryption.
By way of example, only will the clinical trial personnel be able to view or enter the data in the eCRF if they have previously been given user IDs and passwords. What is more, this technological solution integrates blocking functions to prevent unauthorized or suspicious access to the system in the event that a user tries unsuccessfully to access it multiple times.
Other preventive measures consist of granting access permissions exclusively to users holding certain roles, recording which users access the system at a particular moment, maintaining a regular and automatic back-up of the data, and disconnecting a user’s session after a prolonged period of inactivity. All these security measures ensure complete control over user access and prevent fraudulent use of clinical data.
Everything considered, an eCRF is the perfect digital tool to protect the integrity and recovery of the sensitive data collected during a clinical trial. The use of these applications will certainly contribute to safeguarding patient data and creating a more favorable environment for clinical research.
Highest standards of quality and regulatory compliance
Full transparency and compliance with EU, US, and global regulations are undoubtedly a cornerstone for achieving successful clinical research outcomes. The increasing stringency of healthcare regulations in recent years has certainly given rise to real challenges for biopharmaceutical companies planning to conduct research into new drugs and therapies to combat human diseases.
In view of the above, it is imperative to produce validated and regulatory-compliant computerized CRF systems for use in clinical studies, regardless of their design. Compliance with international regulations and standards will guarantee that electronic forms of clinical data collection deliver the same data quality expected of traditional pCRFs.
Modern eCRFs need to adhere to all the quality and security requirements demanded of the clinical research industry. In particular, these web-based applications must be in line with Good Clinical Practice (GCP) guidelines, HIPAA, 21 CFR Part 11 requirements, and other international regulatory standards.
Another measure aimed at ensuring the traceability and integrity of the data collected has to do with a mechanism known as audit trail. Quoting from a study published in the Journal of the American Medical Informatics Association (JAMIA), an audit trail consists of a tool designed to make sure “that the [clinical trial management] system keeps a record about sources from which the data originates, who made changes, when, and what information was changed.” [3]
In other words, an audit trail will make possible to keep track of every creation, modification or elimination of an electronic study record. This entire written record of documents, reports, and correspondence will avoid deviations to the protocol as well as simplify data evaluation and analysis.
Finally yet importantly, bearing in mind that the whole management process will be affected by the implementation of an eCRF system, sponsor companies should also consider the elaboration of a generic audit trail review SOP (standard operating procedure) as part of their quality system (QS). The establishment of new procedures and work instructions is a key quality step that will help to improve efficiency, uniformity of performance, and conformity with industry regulations.
A cost-efficient technological solution
Given the advantages of using an eCRF for clinical data collection, trial sponsors are deeply interested in acquiring this potent software system. However, considering that some sponsors may have a limited budget available to conduct their clinical studies, they are also particularly concerned about the costs associated with the design, implementation, testing, validation, and use of an eCRF.
Software vendors are aware of these budget constraints, which is why many of them are lowering the costs at which their products and services are provided. Delivering an efficient eCRF at a reasonable and affordable price is a commercial strategy that aims, among other objectives, to strengthen relationships with their trading partners and get their businesses off the ground, thus obtaining the greatest mutual benefit.
Notwithstanding the above, and contrary to what might sometimes be believed, an eCRF can significantly cut down on research costs. In practical terms, it can lower the overall cost of clinical data management in a variety of ways.
For example, an eCRF helps to cut down a great portion of the expenses associated with a pCRF, such as printing costs. Additionally, the fact of having to store paper CRFs in place, and process them once they come in, can also imply spending large amounts of money, which proves highly inconvenient.
The ultimate solution to conduct a clinical trial in a successful and cost-effective way is the implementation of an eCRF, which eliminates paper studies and manual efforts. Using this software application entails financial savings for the sponsor as it implies greater accuracy as well as a reduction of expenses in unnecessary resources.
A study published on the BMC Medical Research Methodology website shows further evidence of the low cost associated with an eCRF. According to this academic paper, the total cost per patient differs depending on the type of data collection method employed. Specifically, while capturing clinical data with a pCRF may amount to 1,135€ ±1,234, the price can be significantly reduced (374€ ±351) if an eCRF is used instead. [4]
Therefore, an eCRF is an ideal tool for capturing, managing, controlling, optimizing, and reporting clinical research data at a reduced cost. Through digitalization, process improvement, and a significant decrease in human work and interaction, an eCRF will enhance resource management, maximize investigative site performance, and meet the financial needs of each client.
All the Benefits of Using an eCRF for Clinical Research in a Nutshell
All things considered, not only does an eCRF ensure easier monitoring and improved data security and quality, but it is also an environmentally-friendly and economic tool that contributes greatly to accelerating the development and approval of clinical trials. This innovative solution is gaining support from an absolute majority of stakeholders as it enables simple, fast, and secure data entry and processing for clinical research studies.
In brief, much benefit will accrue to clinical data managers from the use of an eCRF. All these advantages explain why an increasing number of sponsors, CROs, biopharmaceutical companies, and sites are opting for the implementation of an eCRF to carry out all phases of their clinical projects.
Zlynger’s eCRF: Innovative Solutions to Capture Patient Data in Clinical Research
Zlynger is a trustworthy software provider with great experience in offering a wide range of software applications for the execution of clinical trials across the United States, Europe, and worldwide. We constantly strive to maximize the quality and efficiency of all the processes involved in clinical investigations by providing powerful software tools as well as enhanced data management services. Additionally, being aware of our clients’ needs and fully fulfilling them at any time and anywhere is an integral part of our business philosophy.
Today, numerous biotech and pharma companies, academic research groups, university hospitals, and independent investigators benefit from Zlynger’s EDC systems, accelerating data collection, cleaning, and exports in clinical trials of any phase and size.
Ultimately, bearing in mind the significant reduction in time needed for data collection, reporting and analysis gained from Zlynger’s solutions, we are also highly committed to reducing research-associated costs. Definitely, our products and services will bring real value to clinical research projects. For all these reasons, Zlynger is the ideal technology partner for sponsors conducting clinical trials worldwide.
