Challenges and Opportunities for Digital Innovation in Clinical Trials

1. Feasibility and planning

The planning and feasibility stage takes a research question about a compound’s safety and efficacy and turns it into a hypothesis that can be tested in the form of a randomized clinical trial. 

The process begins with protocol design, during which the patient population is identified, and the inclusion and exclusion participation criteria (as well as the control group) are defined. The patient sample size needed to power the trial to produce statistically significant results is determined, keeping in mind that patients may drop out along the way. Protocol design also includes randomization, stratification, and blinding of participants.

During protocol design, appropriate endpoints and biomarkers will be identified to track the impact of the drug. Genetic diseases and cancers require genetic data for biomarker development and patient identification.

Additionally, plans for “informed consent” are developed to provide potential participants with the information they need to decide whether to participate. The sponsor also prepares to collect patient data and monitor patients in a compliant manner. 

Assuming the trial is not virtual, the sponsor will also develop a plan for where the trial will take place. Geographic considerations include the regulatory strategy and the participant profile. To achieve the appropriate number and type of patients, trials often take place at multiple locations and geographies. 

2. Start up 

After planning, the trial moves into “start up.” The sponsor determines what regulatory documents will be needed for submission, sets the budget, and selects appropriate software.  

Though clinical trials are at their core focused on human beings, they rely heavily on software. Software is used to help with recruitment; to randomize patients and distribute medication; to collect, manage, and analyze data; and to monitor the trial. Most trial software comes from third-party vendors. 

Given the large number of software vendors involved in site management, patient recruitment, electronic data capture, and other activities, the selection of vendors is time-intensive and slow. Sponsors may outsource all or part of the trial management to a Contract Research Organization (CRO). 

Similarly, the contracting burden on sponsors at this phase is significant. Contracts are typically needed with CROs, technology vendors, specialized experts, and research sites. With so many disparate contracts, the inherent complexity of trials and legal language, contracting is the leading cause of delay in setting up a clinical trial. 

3. Site selection 

For traditional trials at “brick and mortar” locations, the sponsor must identify and qualify appropriate sites. Sites may be doctor’s offices, hospitals, academic medical centers, community clinics, or clinical research centers. 

In selecting a site, a sponsor seeks a location with both qualified staff and the resources to execute the protocol correctly. Pharma often will return to a previously used site. However, it can be challenging to find sites that have trial experience but are not saturated with trials. A sponsor may need to wait for another trial to end before its trial can begin. 

Any site selected must have the ability to enroll the appropriate patient population successfully. Because sites often run multiple trials and have access to a fixed population, it can be hard to find medication-naïve patients who have not participated in a previous trial, which is often a selection criterion. 

Ideally, sites will enroll a participant population that reflects the genetic diversity of the population for which the medication will be prescribed. For the clinical trial participant populations to mirror the US population, 40% of the participants in trials should be underrepresented minorities. But today, the figure for most trials is no more than 17%. 

To enhance minority participation, sponsors attempt to establish trial sites in communities where underrepresented minorities live. However, locating these patients and identifying sites is difficult to do without sophisticated data. 

Once sites are selected and qualified, trial preparation begins. This involves extensive staff training on the complex details of the study protocols. How well protocols are implemented will depend on the quality of the staff training. Adherence to trial protocols is challenging when staff forget their training or quit. 

4. Recruitment

Patient identification, recruitment, and enrollment is a critical step in almost all clinical trials. It also tends to be one of the most challenging. For patients to participate in a trial, they must be aware of the trial. But “awareness” alone is not sufficient. The patient must also believe that it is worthwhile to participate in the clinical trial and that the trial is safe. When being referred to a clinical trial, patients generally trust their doctors, family, friends, and clergy. 

Patient education to support informed, trial-related decisions is critical during recruitment. Patients may also need assistance to participate in the trial, including the provision of transportation or dependent care.

However, not every patient who volunteers for a trial will meet the trial protocol selection criteria. Finding qualified patients can be particularly difficult for rare diseases, genetic conditions, and certain types of cancer. Achieving genetic diversity across the participant pool can also be challenging.

5. Execution

Execution is the core of a clinical trial, whether the trial is traditional “brick and mortar”, a DCT, or a hybrid. During the execution stage, the patient receives the experimental therapy and accurate, reliable data must be collected from and about the patient. 

Patient data collection takes many forms including blood samples, imaging, and other clinical tests. Data collected may also be self-reported by the patient. Unfortunately, self-reported patient data are often inaccurate or incomplete.

During the trial, side effects and safety data are also collected. Any adverse events must be expeditiously reported. 

Details around medication dosing, administration, frequency, and collection of data are specified in the trial protocol. The goal during execution is to maintain adherence to the protocol. Protocol deviations can have serious implications for patient safety, data integrity, trial timelines, and the overall success of the trial. 

During the execution step of a clinical trial, effective patient communication, education, and engagement are important to maintain participation. If too many patients drop out, the trial may get stalled.

During a trial, sponsors want to monitor the overall performance of the patients, data, sites, budget, and timelines. Much can go wrong.

6. Close out 

When all the data have been collected, the patients stop receiving the experimental therapy and the study is closed out. The data are examined and any errors are identified and eliminated. 

Once all the data are clean, the database is locked and analysis and interpretation begin. During “Close Out” study reports and regulatory submissions are prepared and submitted to the appropriate agencies. Ideally, the patients are furnished with a summary of the results and informed about which treatment arm they were in.