Clario

Lindsay Hughes

The importance of good protocol and instrument design for clinical outcome assessments

Many factors contribute to the success of a clinical trial. These can vary depending on the phase, therapeutic area and indication. However, the bedrock of a successful clinical trial is a well-designed protocol with reliable and valid measurements of biomedical and health-related outcomes. A well-written protocol ensures that good quality data is collected. More specifically, clinical trial data must be of sufficient quality to enable meaningful comparison, have adequate scientific rigor and satisfy regulatory standards. Put simply, a clinical trial is only as good as its data.

Clinical trials data fall into two main categories: biomarkers and clinical outcome assessments (COA). Biomarkers measure characteristics, for example, blood pressure that indicates biological or pathologic processes or responses to intervention. COAs describe or reflect how an individual feels, functions, or survives. Although generally more subjective in nature, COA can and should be subject to scientific rigor and the application of science can make for a better patient experience and improved data quality.  

As technology has evolved and become more present in our daily lives, the ability for technology to improve clinical research has grown. At Clario, we see these benefits every day across our clinical trial management platform. The collection of COA electronically (eCOA) has been a game changer in clinical research. eCOA has facilitated decentralization of trials and hybrid clinical models by making data available to sites and monitors in real time and enhancing the ability to get information from patients in diverse environments. We can integrate this information better and with less effort because of the increased data quality and the ability for validation or adjudication. Electronic data collection allows for custom programmability, date and time stamping, prevention of data omissions and restrictions of data entry to prevent retroactive or forward completion or the review of previously recorded data. As a result, eCOA datasets are more reliable, accurate, and complete as compared to paper COA.

eCOA designs include alerts and compliance triggers to make sure we’re collecting the data that we need.On the backend, we can benchmark the data received from patients with metadata or data from connected devices, creating a robust assessment of the clinical outcomes.The availability of modern technology, including smartphones and tablets in the home, has enabled electronic patient reported outcomes (ePRO) to provide patients with greater flexibility and input in their participation in clinical trials. Clinical trials now routinely offer participants the option of using their own smartphone to enter study data (a method called BYOD—or bring your own device).

It’s easy to get excited about the promise of technology in clinical trials.If you had told us 20 years ago that there was a way to avoid the hundreds of hours and massive room for error introduced by the manual data entry process that would have been cause for celebration.

At the same time, technology cannot replace science, which must always come first when designing a clinical study.

Just as methodological rigor is necessary for the valid and reliable measure of biomarkers, appropriate research methods should be applied to the collection and analysis of COA. There is consensus across relevant scientific disciplines on fundamental methodological principles that should govern the collection of this type of data, but we find that these are not consistently applied to clinical trials. Our scientists have been synthesizing core scientific practices underpinning data collection and instrument design methods from fields including behavioral and social science, psychometrics, epidemiology, nursing and clinical education. While our team has expertise in these areas, we have found that this is not often the case. We are therefore working to make some of these core concepts more accessible across the spectrum of clinical research professionals.

The design of the device or “instrument” being used by the study participant for eCOA is a complex task and application of scientific principles in that process will improve the success rate of the trial. To minimize errors and obtain valuable data for analysis, planning the instrument construction is essential. The most crucial part is to clearly identify the questions that must be answered to support analysis. After establishing what information to collect, the next step is to gather data effectively. One of the most important aspects of instrument design is formulation of the questions. The overall goal is that every respondent understands the question in the same way and the interpretation stays the same over time. Questions should be simple, worded correctly and balanced out throughout the instrument. Response options should be clear and mutually exclusive. Good instruments should show the respondent their time commitment is respected. Stating the aim, giving clear instructions, and a simple thank you at the end, pay off in the form of higher response rates. These are only a few examples from the spectrum of scientific recommendations our team proposes forCOA design. Not only will these improve the quality of the data, but they will also ensure the data meets regulatory standards.

While eCOA, such as ePRO and patient diaries, need to appear simple and be easy to complete, the science and operational expertise behind delivering them is complex. They should be carefully designed to capture high-quality, rich data while also considering the patient experience and following core scientific principles for data collection.