In WCG’s annual report on industry trends and insights, Chief Medical Officer Lindsay McNair writes that “2020 has been a remarkable year for clinical research in many ways. The COVID-19 pandemic disrupted traditional practices and created chaos for sponsors, regulators, researchers and research participants.”

“But our adjustments and movement toward recovery also brought us new flexibility, new collaborations and a focus on the importance of both patient-centric research practices and diversity. There have also been incredible achievements by the teams moving forward vaccines, potential therapies and new diagnostics for COVID.

“As we look back at 2020, the team at WCG is also looking ahead. Our subject matter experts talk about what they see as significant issues and trends in the clinical research world; what they are looking at and looking forward to for 2021.” Here are edited excerpts from the report:

Mark Opler, Chief Research Officer, WCG MedAvante-ProPhase

The technologies and systems adopted to “pandemic-proof” trials in 2020 have become permanent fixtures of the landscape. FDA fast-tracked programs, long-running studies reading out and other narratives will come to some exciting conclusions in the next 12 months. It is interesting to note that some of the new study paradigms that have surfaced in the past few years are demonstrating durability, particularly the adoption of remote assessment as a modality and the blurring of lines between brick-and-mortar (traditional) and virtual trials.

Some important evidence continues to illuminate the root causes of trial failure, highlighting the vital need for better study designs to promote smaller, high-powered trials, careful endpoint selection to ensure validity and reliability, and bolder strategies to promote data quality. The promise of 2021 lies in our ability to capitalize on lessons learned during a crisis, our determination to integrate both traditional and novel approaches to research problems, and our willingness to invest in making clinical trials better, rather than just bigger.

Arturo Morales, Vice President, Data and Technology Solutions, WCG Analgesic Solutions

Recent breakthroughs in data analytics have shown that it is possible to identify data quality issues in blinded trials that may cause them to fail, and that it is possible to deploy mitigating interventions that can correct these issues without introducing bias. That means that we no longer must wait until the trial is completed to identify problems, and we have a chance to intervene early and minimize their impact.

The key is to identify data quality biomarkers that can be used as surrogates of underlying data quality issues that may make it difficult (or impossible) to separate drug from placebo (or other comparators) due to factors unrelated to the drug’s effects. One can then use those digital biomarkers to monitor blinded trials and systematically deploy clinically informed interventions where applicable, to address issues as soon as they are detected, thereby protecting the trial’s outcomes.

Bob Dagher, Chief Medical Officer, WCG MedAvante-ProPhase

Industry leaders must adapt existing processes and study procedures at the core of any given trial. The choice and mode of administration of the study endpoints, whether in-person or via remote assessments, become even more important when considering all possible study design options. Certain types of clinical outcome assessments are more easily amenable to remote administration than others. When conducting remote assessment, the ability to maintain a high level of engagement and sustained effort on the part of the subject is a critical determining factor for standardizing and validating a new mode of administration.

In order to maintain consistency across assessments, it becomes critical to be able to adapt the technology equipment and tools to the use-case, devise item-level guidance for various scales, and allocate training and dedicated support toward participants and their supportive environment.

Where quality data and interpretability of results are the guide for any informed decisionmaking, expertise is required to de-risk the clinical trial from the added dangers the current pandemic has brought upon us. This new era is foreseen to be especially prone for a spike of new confounders and factors that can negatively impact study integrity. Ensuring additional layers of protection of study endpoints, by reducing the level of “noise” in the signal, is an especially important step in 2021.

Nathaniel Katz, Chief Science Officer, WCG Analgesic Solutions

One of the most interesting directions I see in clinical research is integrated endpoint protection. We know that for a clinical trial to be successful, much depends on patient performance. Some expectations are obvious, like adhering to medications or to entering data in electronic diaries, although even for those obvious expectations it is appalling how little effort is expended to optimize these tasks. Other expectations are at least as important, but far less obvious, such as reporting symptoms accurately or keeping expectations of personal benefit neutral (the main driver of the placebo response).

To increase the reliability of clinical trials, an automated and integrated approach to capturing accurate patient-reported data could include such measures as validated patient training, handheld e-diaries that recognize when patients are entering “implausible” data and provide training tips so patients can correct those entries before they become part of the clinical database, and central statistical monitoring that detects aberrant patterns in the clinical data and presents automated, customized retraining to patients without any human intervention.

Sandra Smith, Senior Vice President, Clinical Solutions and Strategic Partnerships, WCG

Oncology will be a predominant therapeutic area in clinical trials in 2021 as the quest to transform cancer care via “precision oncology” unfolds. Ongoing interest in biomarkers and the increase in immuno-oncology targets are keeping the pipeline filled with hundreds of therapies in development across all phases. Combination options will continue to be explored, combining therapeutic agents as well as multimodality therapies, including novel surgical and radiotherapy approaches.

The abundance of new agents led to innovative trial designs, adding complexity in oncology trials with a resultant increase in patient and site burden. Sponsors are increasingly aware and are actively seeking the patient voice in every aspect of the clinical trial design process. Frequency of visits, use of digital health, patient concierge services, less invasive procedures all support a focus on patient-centered trials.

Ros Cheetham, Senior Vice President, Clinical Solutions and Strategic Partnerships, WCG

I believe that in 2021 the biotech sector of the market will continue to drive growth in both the number of clinical trials and drug approvals. One projection shows that biotech will reach more than $775 billion in value within the next four years. The current COVID-19 situation is certainly driving some of the growth as companies seek to develop vaccines and treatments for this devastating disease. However, I also see other areas of exponential growth for the biotech sector. Personalized medicine due to advances in genetics means that other exciting areas of medicine are opening up in areas such as neurology, cardiology, oncology, ophthalmology and rare diseases.

Janet Wittes, Founder and President, WCG Statistics Collaborative

Next year, the industry is likely to see an explosion of vaccine development for viral diseases given the new understanding that mRNA vaccines are likely to be highly effective. The dramatic success of immunotherapies in cancer will probably encourage the development of molecularly targeted treatments for other diseases with an emphasis on patient-specific interventions.

While many trials, especially of diseases of the cardiovascular system and conditions like diabetes, will likely continue to study a large number of participants, 2021 may well see many more very small trials of rare diseases with mature approaches to utilization of historical controls. Perhaps most importantly, the promise of effective COVID-19 vaccines and treatments may lead to the public’s understanding that each of us has a vital role in development of products to benefit the public health.

Geoff Schick, Senior Consultant, Site Strategy, WCG

With the continued economic downturn from the pandemic, research sites in healthcare systems and academic medical center settings will be increasingly challenged to prove the business case for clinical trials research. Sites will have increased pressure to perform cost effectively and to develop revenue streams beyond enrollments into clinical trials research.

Jonathan Seltzer, Chief Scientific Officer, WCG

Recent advances in technology have demonstrated the possibility that remote clinical trials (also referred to as “virtual” or “decentralized” trials) can provide increased cost efficiencies. Regulators concurred, as the FDA and European regulatory agencies released COVID guidances that endorsed remote clinical trial visits. It is likely that trend will not end with the pandemic — in fact, most feel it will continue to accelerate. We can expect increasing regulatory attention on data integrity as well as demonstrating that patient safety can be preserved using remote visits.

David Forster, Chief Compliance Officer, WCG

The evolution of privacy regulations will continue and will need to be balanced with the requirement to maintain appropriate documentation of clinical trials. In particular, the ability to transfer personal data among countries to conduct global studies and create submissions appropriate for drug regulatory agencies around the world can be impeded by privacy regulations and court decisions.

In 2021, we are likely to see additional developments in the privacy sphere, and with each change there will need to be consideration of clinical trial recordkeeping, as both privacy and access to improved medical interventions are good for individuals in every country.

Linda Sullivan, Executive Director, WCG Metrics Champion Consortium

Adoption of quality by design, risk-based quality management (RBQM) and centralized monitoring (CM) approaches detailed in ICH E8 — General Considerations for Clinical Studies and ICH E6(R2) — Good Clinical Practice will accelerate in 2021. Sponsors have implemented those approaches during the COVID pandemic out of necessity. Protocols were streamlined, remote and centralized monitoring programs were adopted, and reduced/targeted source data verification approaches were embraced.

Looking ahead, organizations will implement those approaches across their portfolio of studies as nonCOVID clinical trials are restarted. To support successful implementation of these programs across larger portfolios of studies, organizations will need to address two important areas: lack of data needed to support RBQM and CM data analytics and a shortage of staff trained to interpret and act on the data. Those challenges can be addressed through the adoption of industry-based performance and quality metric standards that improve the quality and consistency of the data available to data analytic programs. Additionally, risk management and root-cause analysis training programs developed specifically for clinical research staff can be deployed to close the workforce skills gap.