Scalable Considerations to Avoid Clinical Research Pitfalls

Clinical research would not be possible without the participation of patients who donate biological specimens (biospecimens) that help to confirm specific biological changes (i.e., biomarkers) that result from a clinical investigation. Guidelines for the collection of human biospecimens, originally developed by a committee appointed by the National Institute of Health (NIH), outline procedures and best practices for how biospecimens should be handled and stored to ensure proper stewardship.

When the proper specimen tracking systems are in place, such as warnings and transfer notifications, clinical trial sponsors ensure a greater oversight on the status and viability of biospecimens that become essential for the overall understanding and impact of their treatments. Although technology has improved the traceability and management of biological specimens, these systems still require management, especially during unexpected operational disruption or complex developments due to study design amendments or logistical situations such as global expansion.

In this article, we will review fit-for-purpose oversight and tracking solutions and key challenges any sponsor will most likely encounter and provide suggestions to address and mitigate risk regardless of company size.

Fit-For-Purpose Biospecimen Oversight Process Recommendations for All-Sized Companies

Regardless of the biomarkers selected for clinical research – the characteristics that are objectively measured and evaluated as an indicator of normal biological processes, or pharmacologic responses to a therapeutic intervention – there are key steps that must be established to take full advantage of the samples and data collected throughout the trial to ensure viable treatments and selections.

Regardless of company size, here are our suggestions:

• Develop a comprehensive end-to-end sample management plan that include sample flow stabilities and temperature requirements, outline of milestones and sample touchpoints, key stakeholders’ roles, and responsibilities with escalation plan, and when to visit forecast, planning alerts, and logistics pre-assessment details
• Supplier approval: To help improve better sample shipment receipt and on-time testing, courier logistical capabilities should be assessed and piloted to assist in streamlining specialty testing.  3^rd Party laboratories utilized for storage and/or analysis of the biomarkers must be approved as vendors prior to utilization. If validations of new biomarker assessments are required, this process must be confirmed and completed prior to any sample analysis  
• Verify courier: Courier transport of samples must also be verified and monitored to ensure point-to-point continuity from the site to the laboratory when temperature requirements and sample conditions are critical
• Incorporate early logistical assessments with lane verifications, early dry runs, and early collaboration with shipping partners. Evaluate sample stability with shipping options and lab and/or site locations; and ensure strategic shipping with time and cost analysis
• Biospecimen tracking: electronic tracking and management of biomarkers can be initially managed through ad hoc software adaptations. However, an agile approach (i.e., breaking down the process into several phases) to biomarker system management should be considered as early as possible to accommodate future program growth and increased complexity with growing patient numbers
• Manage and oversee biospecimen tracking: management of biospecimen tracking, sample collection, and analysis that should include validations.. The startup begins with the initial step of obtaining Informed Consent and providing explicit language regarding the collection, storage, use of biological samples taken from the patient as well as potential removal or exclusion of samples from analysis or use
  • Additionally, much of this (de-identified) information needs to be incorporated as part of the samples’ metadata or patient sample profile to ensure optimal traceability and management. The patient profiles can also be used to help assess the viability and acceptability of the biological samples prior to any biomarker assessment
• Monitor technologies for high value samples through tracking shipments in real-time from origin to destination with real-time temperature monitoring devices and integrated sample tracking labels. For out of country shipments, seek couriers that provide dry-ice replenishment services after clearing customs
• Biomarker analyses: Planning for biomarker analyses can be further organized from ongoing reviews of the sample profile data (i.e., sample expiration or storage integrity) that can ultimately improve the selection and planning of analytical testing.  By aggregation of viable samples, batch size runs can be optimized to reduce potential bias through selective group analyses, leading to maximization of each analytical run
• Biomarker verification: Confirming the validation of biomarker selectivity and sensitivity for selected laboratories can provide options for regional analyses, back up laboratories, or assessing laboratory skills should other biomarker options be considered

Four Key Challenges and Suggestions for Biospecimen Tracking and Analysis That You’ll Likely Encounter

1. Handling Program Expansion

We’ve observed that program expansion (i.e., multiple studies) and global investigational presence exponentially complicates the oversight and sample management process. However, the greater the selectivity of the assay – a process of analyzing a substance to determine its composition and quality – and inherent simplicity of the biomarker procedures used, the more there will be adaptability to other sites and new laboratory facilities. Biomarker assays should also involve minimally invasive techniques, be simple to perform, and provide rapid and consistent results at a low cost.

Biomarker assessments of specific biomarkers can be driven based on literature and previous data of product programs. However, broader development of biomarkers may be necessary due to the limited clinical data or surrogate markers for a particular disorder.

2. Managing Protocol Amendments

Frequent amendments to clinical trials are common and they can have a domino effect on other assessments in the trial, such as managing biospecimen collection and tracking. Because advanced therapy trials can lead to additional specimens collected, here are a few best practices to help manage the changes:

• New technologies — Utilizing technologies such as digital ink pens can be used in collaboration with paper forms and downloadable encrypted forms to capture patient information with virtual accessioning of sample collection from the pre-populated information in the sample tracking plan. This tool helps sites track compliance with the protocol and minimize sample collection errors. Web-based portals provide real-time sample information from virtual accessioning
• Virtual central labs help to manage all the samples collected, stored, and tested. These laboratories keep track of what’s been collected at a site before it even gets shipped. They can also provide a virtual accession number and verify the data for each sample, so you have a single, virtual source of data for all your sample collections before being shipping to respective labs
• Sample tracking solutions should be evaluated through early planning and conducting a risk assessment before making the final decision

Early collaboration between sponsors and central lab partners is increasingly important especially in advanced therapy studies. Central labs need to support study complexity and globalization demands of advanced therapy trials by providing solutions that adapt to study needs as they arise. As we all know that issues can arise throughout any point of the sample management lifecycle, the key is having the ability to act quickly and proactively to ensure swift resolution with minimal impact to the trial.

3. Managing and Monitoring Shelf Life

Managing shelf life is also a challenge, so establishing a good identification process for all samples is essential to managing sample shelf-life, baseline and post assessments, study number, and other key medidata that helps with selection of processing or destruction. As clinical programs begin to evolve, storage and management of specimens becomes more complicated, requiring medidata tracking, and sample reconsideration of initially selected biomarkers as more clinical data becomes available. 

4. Working with Scalable Financial Resources

Managing financial contracts can become increasing difficult as projects change and expand. Knowing the costs per sample can help improve your budget especially if samples can be systemically removed (if not viable), group shipped, and maximally grouped for analyses. Although management and tracking of biomarker samples can be aligned with established clinical and analytical reporting systems, continual oversight activities can be put in place to ensure only the viable and appropriate samples are analyzed.   

Conclusion

Ultimately, planning to use biomarkers in clinical research requires careful consideration of basic sample processing, sample management, storage, viability, storage, and analysis. However, initial plans should also include programs for growth and expansion. Sample analyses should be assessed early to ensure any expansion can be accommodated and managed cost effectively. Regardless of company size and program size, there are opportunities available and successful approaches to ensure successful clinical trial data management through a thoughtful biospecimen process.

If you would like to discuss this further, please be in contact.