Key Clinical Trial Considerations for the New Normal and the Future

A great many new and varied approaches to clinical trial management are being adopted during the COVID-19 pandemic through the help of virtualization tools, strong partnerships, and regulatory guidance. Despite the upheaval this year and last, there appears to be a silver lining largely due to the systemic changes leading to the remarkably quick development in adapting trials to accommodate different environments and the incredible speed at which COVID-19 vaccines have been developed and administered. Regulatory guidance has accommodated this abrupt shift. In this article, we will cover the key factors needed prior to adapting to patient-centric clinical trials. 

For starters, there are quite a few differences regarding attaining and disseminating patient-level data in a decentralized or remote trial setting versus the traditional way an in-person study is designed. Telemedicine or remote visits, for instance, have traditionally only been used for patient-physician consultations in the health care setting. However, the value of telemedicine for use in clinical trials has grown ever more promising due to the greater access to research and reduced attrition it can deliver.   

Data collection methods tend to be the primary component that changes with decentralized clinical trials in comparison to in-person studies. With remote trials, the engagement with digital technology for data capture provides the potential to receive information at a higher frequency, which means more data is available. 

Challenges in patient-centric trials  

Another major difference occurs with the effectiveness of communication among patients and clinicians who are no longer involved in face-to-face interactions. With remote trials, the process of sharing information with some patients can be impacted because the patients can become either more or less forthcoming. It depends on how comfortable they feel about having virtual interactions and their comfort levels with the use of different methods for data collection versus in-person visits. Additionally, with remote trials, methods such as traditional phone calls between clinician and patient are sometimes replaced by remote monitoring using virtual tools/dashboards. In the latter case, patients need to feel that their voices are still being heard by the clinicians to be comfortable with the processes and methods being used.   

Dissemination of information is an additional important consideration. For instance, when using remote monitoring tools, clinicians should consider the quantity of information and details that are made accessible to their patient, especially if the patient can assess their information through dashboards. For example, considerations on whether to conduct in-person vs. remote should be made when returning lab measures to a patient because at the in-person visit, the clinician would likely explain to the patient and would be able to better read the patient’s body language to know whether additional clarifications would be helpful. Something as simple as details of the normal ranges could be concerning to the patient if, for instance, the normal for that patient happens to not be within the normal range for the general population. Whilst from a medical perspective there are no concerns for that patient, the relaying of such details to the patient requires careful management to avoid the patient misconstruing the information.   

Wearables in patient-centric trials 

As wearables evolve, it appears that both consumer and clinical grade wearables could bridge some of healthcare’s most considerable gaps. However, it’s still uncertain if consumer wearables will ever gain the credibility or even functionality of medical-grade devices. One thing is for sure, both continue to contribute to the growing wave that is Big Data.   

With consumer-grade wearables, trial professionals often need to assess how they can ensure data collected from wearables is accurate, considering how difficult it can be to ensure patients keep their consumer wearables charged and in good working order. Additionally, they need to rely on the patients to wear their devices correctly and that the data is downloaded correctly and is secure.  

When using wearables, there are key questions to consider including: 

  1. What and why is the data being collected?
  2. Which type of device will be used (consumer vs. medical grade or BYOD)?
  3. How much data is used and what information is shared with the patient?
  4. Who owns the data? 
  5. What is the frequency of data sharing and data flow?

It is important that the trial sponsor think about what data they need and why the specific information is being collected. At this stage, considerations should be made regarding the format of the raw data that is provided from the device selected and how the information should be analyzed. It is also essential to determine the frequency of data collection. As devices collect data continuously, the question is two-fold. First, assess the granularity of the data available from the device, such as minute-by-minute summaries vs. all raw data. Second, determine the expectations around wear time. Vetting this out ahead of time helps to drive the device selection, e.g., BYOD, consumer devices, or medical-grade device options.   

Due to the pandemic, companies see patients as informed collaborators whose participation could be key to furthering the overall success of a trial. Hence the term and greater usage of “patient-centric trials.”  

There are challenges concerning access to the data, data format, frequency of data extraction, and validity of the data. Different types of devices have different challenges in accessing the data, e.g., BYOD vs. medical grade devices. BYOD is playing a more active role in patient-centric clinical trials. If BYOD simplifies the clinical trial process, sponsors may achieve improved patient compliance, higher-quality data, and potentially lower operational costs.   

Data flow and collection 

Once a device is chosen, it is vital to understand the flow of data, from the extraction of data from the device to the storage of the raw data, of which there is likely to be a lot, through to the summarized data for the trial team. Certain measures should be put in place to ensure the flow is efficient, successful, and secure. Deciding who is responsible for different parts of the data flow is vital to ensure the information will disseminate correctly, and with consideration to upgrades and changes by the manufacturers, who will monitor and update the workflow. Therefore, it is important to factor in how this will this impact the final analysis.   

Generally, the trial sponsor would determine, with input from the clinicians, if the data collected from wearables will be used during the trial, and if so, how? The rationale for using wearables is assessed at the beginning of the trial and performance is monitored throughout the trial. It is important to factor in whether the trial will require all the data collected such as activity, steps, and location information or just certain aspects. How will all of this be controlled? Expectations for the patient’s wear time of the device must also be decided regarding the need to detect, monitor, and/or manage non-wear time during the trial.  

Such considerations as to whether the clinician should discuss the data from the device with the patient will need to be assessed, as well as how and what elements are to be included. If the patient is expecting to have a discussion, the patient may become disengaged if it doesn't happen. Additional areas may need to be addressed if device information doesn't match the information provided from the patient. For example, if a patient reports they are walking 10 miles a day, but the device only records 1,000 steps, this issue needs to be resolved.  

Accuracy and standardization 

One fundamental challenge for trial teams comes when they need to ensure their patient-level data collected remotely is accurate, complete, and in line with applicable regulatory considerations.  

Standardizing remote data collection across participating sites, trial participants, and study visits can reduce variability in the data. Prior to deployment of remote data collection, trial sponsors need to evaluate the feasibility of the remote data collection method. It is vital to have trial sites and participants prepared and fully able to comply with the data collection methods chosen. Site training may also be required to ensure systematic data collection and the need to uphold patient confidentiality. In lieu of attaining all pertinent information that would normally have been collected during a face-to-face study assessment, a video assessment documented with date and time should be included in the study source documents. To preempt the potential of missing data in remote monitoring, notification technologies that remind and prompt the patients/participants to report their information should be deployed.    

The Delicate Balance 
Research professionals continue to try to balance as best as they can the need for accuracy, efficiency, thoroughness, and other positive aspects in their trials, all while trying to reduce patient burden. The more unobtrusive the trial, the more favorable for patients and the clinical site. Spreading out the assessments, for example, and decreasing the quantity of assessments performed at each visit is something sponsors may want to consider. The implementation of verbal and/or electronic reminders in patient reporting can be helpful. It could likely reduce the amount of missed assessments/reporting and provide a better outcome. Training for clinical sites on how to efficiently capture study data remotely could be a worthwhile investment.  

Conclusion 

The advent of decentralized or remote clinical trials has created both challenges and opportunities for accurate data collection. With efficient processes in place, it has been proven possible to ensure data flow is accurate, successful, and secure. Clearly, the expansion of telemedicine approaches with patients offsite has created an opportunity for both mitigating patient risks in a face-to-face setting as well as and allowing the patients a more comfortable setting in which to deliver data to clinicians during a trial.   

As wearables (consumer, clinical grade, and BYOD) continue to gain traction they, along with telemedicine approaches, may become another important asset in closing some of healthcare’s considerable communications gaps. However, it’s still uncertain if consumer wearables will ever gain the credibility, or even functionality, of medical-grade devices.   

One thing is certain, both telemedicine and wearables will continue to contribute to widening opportunities for data collection. Continued adoption of digital technologies, to not only capture data at greater frequency and speeds, may also lead to improved patient collaboration and the potential for lower overall operating investments.  .