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Applied Clinical Trials October 2021

New support models range from flexible software platforms, IROs, and DROs.

The Evolution of Site Selection

SGS officially opened its new clinical pharmacology research center on the Antwerp University Hospital site on October 26, 2021, in the presence of Frankie Ng, SGS CEO.

The newly built SGS CPU, aimed at early phase research, is located next to the University Hospital of Antwerp (UZA). Its proximity to UZA reinforces scientific collaboration with a network of specialists and techniques.

This new CPU is a modern, sustainable, and innovative facility. With a capacity of 110 beds, a wide range of settings can be provided. Study participants stay in two to 8-person rooms, or in individual rooms, and have access to comfortable living and leisure areas. A high-care room allows follow-up during testing of new drugs. Two specialized quarantine units are available for controlled investigation of infection models or controlled human infection models (CHIM). In recent years, the SGS CPU has conducted the first malaria challenge studies in Belgium with its own developed H3N2 (flu) virus.

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SGS Opens New Site in Belgium

Imaging Endpoints has announced that it has established a new office in Shanghai, China, home to rapidly growing pharmaceutical and biotech innovations in Asia. Imaging Endpoints has expanded its globality to include eight offices across six countries and three continents.

Imaging Endpoints works with nearly all imaging sites globally that participate in clinical trials, and the expansion of operations into Shanghai will enable key team members, such as project managers and radiology experts, to work real-time with their counterparts in China and throughout the Pacific Rim.

More on Imaging Endpoints Shanghai Operations

Imaging Endpoints Establishes Operations in Shanghai

Diaries are often an essential component of a clinical trial, not only for gathering patient-reported outcomes (PROs) but possibly even for determining a study participant’s eligibility. If that diary becomes complex however, this will impact everyone involved, from the sponsor and eCOA designer to the study participant and site. By understanding the ways complex diaries are problematic, sponsors can better assess if these complexities are necessary.

Sponsors who overcomplicate their electronic diary can expect delayed timelines due to the extensive design, build, and test time required from the eCOA designer. Diaries that collect excessive data can overwhelm and confuse patients, which can lead to training and support burdens for site staff as well as lead to higher dropout rates. Complex diaries can also make it more difficult for sponsors to analyze the data.

This is not to say that in some instances a complex diary is not warranted. Seizure studies, for example, can be quite complex because of the need to collect when symptoms occur, the classification of the seizures, and any rescue medication used. However, many studies do not require this level of detail. The key is to recognize when a diary is more complex than needed, so that adjustments can be made that lead to a simple, yet effective version.

Sponsors can simplify diaries by taking a closer look at the three common sources of complexity: assessment complexities, scheduling complexities, and study-level factors.

There are aspects within the diary assessment itself that sponsors should avoid. For one, no more than one question should be displayed on the screen at any given time on any device—regardless of the screen size. Not only will this single-item format keep participants focused on specific questions, but the format is considered a best practice by the ePRO Consortium and Clinical Outcomes team at Oxford University Innovation, and therefore, is an industry-wide approach.

In addition to limiting the number of questions displayed on the screen, the instructions should be as concise as possible. It is highly unlikely that study participants will read lengthy directions every day, so it is recommended to be succinct and bold key information. This will help patients absorb the most important points and submit quality responses. Irrelevant instructions, such as prompting patients to ‘select one answer' when the system is configured to only permit one answer should not be used. Irrelevant instructions, such as prompting patients to ‘select one answer' when the system is configured to only permit one answer, should not be used. Nor should instructions that are obvious via on-screen visuals. We also suggest reserving the use of ‘please’ for when additional, out-of-the-ordinary actions—like contacting the site—are required. Sponsors who overuse terms like ‘please’ will risk the words losing their meaning.

Keeping text to a minimum applies to the patient’s responses, too. Free text should not be used since patients may submit personal or confidential information. Furthermore, free text demands more time from participants to complete as well as study teams to review and clean prior to analyses and analysis of free text options is generally limited.

Excessive branching caused by a multi-select design forces study participants to consider their symptoms twice: first if the symptoms occurred and then again to rate its severity. 

This format tends to result in questionable data, especially if it is not intuitive to patients that they can initially select more than one answer. Even worse, this design provides the participant with the opportunity to report no issues to bypass the follow-up questions. It is also more difficult to program and test. Instead, the recommendation is to individually present all the possible symptom items.

For some studies, assessments must be completed for a specified number of days prior to a clinic visit. While this may be an unavoidable complexity, the biggest issue lies with the method in which the data collection is activated. For instance, triggering the diary’s availability based on scheduled visit dates is problematic since these dates often change and sites use a separate system to reschedule and can often forget to update the diary’s system. The result is diaries are unavailable when the patients need them, and sponsors do not collect the data as the protocol dictates. It is easier for everyone involved if sponsors pre-specify incremental dates throughout the study. If sponsors 

 have the data prior to a visit or have concerns the at-home and on-site data will overlap, the site could provide an access code to participants when they remind the participant of upcoming visits. Alternatively, sponsors can choose to make the diaries always available, however this leads to considerably more data being collected than the sponsor may find acceptable.

When considering scheduling of diaries, sponsors may struggle with deciding if the diary should be completed once a day (Daily Diary) or episodically. Episodic diaries allow multiple events to be recorded on a single day. In urology studies, this type of diary enables patients to submit when urination events occurred. This reduces burdens on study participants as they don’t have to remember each symptom occurrence at the end of the day. By permitting the data to be submitted at the time of the event, sponsors can improve data quality.

Despite the misconception that daily tasks burden participants, a daily diary is recommended for most studies as completing an assessment every day at the same time will foster a habit in study participants and improve the diary compliance. A daily diary—even if it only consists of one question—will keep participants engaged too. If weekly or monthly diaries are required by the protocol, sponsors can add these questions to the existing daily assessment or automatically launch the additional questionnaires once the daily assessment is completed.

Finally, a sponsor should steer clear of study-level complexities, including retrospective entry, and the collection of adverse events (AEs) and concomitant medications (con-meds) in the eCOA solution.

Sponsors who permit retrospective entries do so because they fear they will miss important data. Ironically, retrospective entry is more likely to lead to missing data and adherence issues as a data entry habit was not established among participants. Furthermore, it is common for participants to get confused regarding the retroactive entry’s time frame since many sponsors only customize the initial screen and do not reference the day in question on subsequent questions. In addition, by allowing retrospective entry, sponsors introduce recall bias. Recall bias occurs when patients are influenced by their current state at the time of recollection and respond inaccurately. The FDA recognises this issue and states in their PRO guidance that “items with short recall periods or items that ask patients to describe their current or recent state are usually preferable.”

Unlike retrospective entry, every protocol requires the collection of AEs and concomitant medications. A diary, however, is not the right tool to collect this data. For one, AEs require trained clinicians for evaluation and reporting. The eCOA companies that deliver diaries do not have the necessary clinicians nor mechanisms to promptly report events as dictated by the FDA. Because of this, eCOA data collection technologies—including diaries—should not be considered the mechanism for documenting AEs.

Since a patient’s concomitant medications typically do not change during the study, capturing this data with a standard electronic data collection (EDC) system at study visits can prevent unnecessary burden on patients and sites as well as reduce diary complexity. Site staff can periodically confirm with patients at the on-site visits that the concomitant medications have not changed.

Educated sponsors who can recognize when diaries are overly complicated and understand their impact can ultimately make better informed decisions. Eliminating the common sources of complexity—assessment, frequency, and study-level factors—will improve the clinical trial experience for everyone involved. A focus on the most important data, the primary endpoints, will enhance the data quality and reliability.

is a Senior Scientific Advisor for Signant Health.

Center for Drug Evaluation and Research. “Patient-Reported Outcome Measures: Use in Medical Product Development.” U.S. Food and Drug Administration, FDA, Dec. 2009, www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims.

Sponsors can simplify diaries by taking a closer look at the three common sources of complexity.

The Importance of Simple Clinical Trial Diaries 

Trialbee has launched the Trialbee Honey software platform. Honey was built for patient recruitment teams to recruit and engage highly qualified patients while aiming to optimize enrollment timelines through real-time analytics.

Created to provide transparency into patient recruitment and foster convenient communication and engagement, Honey’s analytics dashboard enables study teams to consolidate participants recruited from multiple sources and increase enrollment conversions.

Trialbee Announces Trialbee Honey

COVID-19 physical distancing requirements forced change in how traditional clinical trials were conducted and a new Informa Pharma and Oracle study shows the industry is not looking back. Of the 251 people surveyed, 84% implemented alternative tactics to continue their existing clinical trials and/or start new trials during the pandemic. Of those respondents, 82% said these approaches had positively impacted their clinical trials overall. Looking to the future, 97% indicated their organization would continue using at least one of these new methods moving forward, leading with remote monitoring and video (eHealth) visits.

The survey, Clinical Trial Management in a Post-Pandemic World, polled participants from biopharmaceutical and medical device companies, as well as CROs involved in the operations and management of clinical trials from July to September 2021. Respondents, who were largely from North America and Europe, with others from APAC and other regions, were asked about changes made to their clinical trials during the pandemic, the effect of these adaptations, and the impact of these changes on the future of clinical trials.

Of the various methods noted, 45% of respondents said they had adopted remote monitoring in their trials during the pandemic, nearly doubling the number of respondents who reported using remote monitoring a year ago. Among the newly adopted methods that companies plan to continue to use post-pandemic, remote monitoring (32%), video visits (28%), electronic health records (24%), and phone visits led the pack (24%).

The most common positive impacts of the alternative approaches adopted during the pandemic included more timely data access (48%), improved flexibility for patients (41%), and increased speed (38%). 

When asked about their confidence in the data generated by newly adopted approaches, 92% of respondents stated they were equally or more confident in the data collected from these methods, compared to data collected via pre-pandemic methods. This was a marked change from the 2020 survey when nearly half of respondents said that data reliability and quality (50%) and data collection (45%) were key concerns in adopting decentralized clinical trials. This significant increase in confidence supports the industry’s continued progress towards more decentralized models.

The study also found that improving the patient experience is a priority. Many respondents (61%) believe allowing patients’ choice will have a positive impact on clinical research and well over half (58%) said that their organizations plan to give patients the option to choose how they participate in clinical trials moving forward.

As the shift to decentralized trials continues, survey respondents expect their organizations to continue using hybrid (44%) and fit-for-purpose (42%) models after the pandemic. Of the four models considered—site-based, fit-for-purpose, hybrid, and decentralized—respondents expect the use of the site-based model to decrease the most (24%).

Pandemic-Driven Changes in Pharma Here to Stay as New Clinical Trial Models Take Hold

Advarra has announced the launch of Site IQ. The platform builds on Advarra's experience as the provider of practice management solutions for clinical research to deliver an integrated set of site and principal investigator insights to enable smarter site selection. The Site IQ platform provides customized data analysis to help sponsors and CROs make informed decisions in their investigative site selection and feasibility processes.

Advarra Site IQ delivers insights to drive study startup by supporting protocol planning and site selection processes. Site IQ informs intelligent site selection by leveraging comprehensive data across experience, capacity, quality, performance, and patient eligibility. Data is derived from Advarra's data as well as third-party partner data. As such, Site IQ reflects insights based on actual study and performance data, not estimates or self-reported information.

Advarra Announces Site IQ

Calyx, the eClinical and Regulatory solutions and services provider, has announced that one of the world’s Top 10 pharmaceutical companies executed a contract to continue its use of the Calyx Regulatory Information Management (RIM) system for critical submissions of clinical development data to global regulators through 2026. Calyx RIM enables pharmaceutical companies to compile and submit comprehensive dossiers to global regulatory authorities.

Calyx RIM Selected by Top 10 Global Pharmaceutical Company

Calyx RIM Selected by Top 10 Global Pharma Company

The clinical trials industry is beginning to reemerge from the pandemic and is taking a new direction in the new post-pandemic reality. The pandemic has forced the clinical trials industry to adapt to new ways of thinking around patient-centricity; politicization seemed to have generated a renewed interest in clinical trial diversity inclusion, surging demand in decentralized technologies is transforming research, and advances in artificial intelligence (AI) and data access are allowing for new opportunities in RWE predictive research and early patient engagement. These were the main themes discussed at Disruptive Innovations to Advance Clinical Trials (DPHARM) 2021.

One of the main topics included recruitment challenges with COVID vaccine development during the pandemic. Diane Montross, Sr. Director of Patient Recruitment and Retention at Moderna, discussed that while the COVE study initially saw many volunteers, enrolling 30,000 patients in a short timeframe and ensuring diversity inclusion was a big challenge. Accordingly, Moderna needed to expand its recruitment vendor access; however, another challenge included vendor onboarding. To elaborate, specific vendor qualification and onboarding stages took time, such as the request for proposal (RFP) process, bid defenses, procurement and contracting, relationship building, vendor management, and governance, and performance tracking analysis. Hence, they partnered with Citeline Connect, which centralized the process, enabling Moderna to rapidly engage and ramp up numerous recruitment vendors. As a result, within two months, Hispanic/Latinx patients increased from 14% to 20% of the entire study population, and African American patients increased from 5% to 10%, helping to achieve its diversity inclusion and recruitment goals.

This year, diversity inclusion has been an essential topic within the biopharmaceutical industry, as evangelized by 

. Lloyd Miller, VP of Immunodermatology Disease at Janssen, discussed his organization’s approaches towards enhancing diversity, equity, and inclusion in clinical trials. Miller indicated that while FDA advises the biopharmaceutical industry to improve diversity by including patients who will use’ medication post-approval, safety and efficacy differences between patient populations are often not explored in datasets because of lacking statistical power. Nevertheless, the industry has made strides in clinical trial diversity inclusion; for example, from 1995-1999, white patient populations represented 83% of trials, whereas, in 2019, they represented 72%. Of particular note, Latinx patient populations increased from 3% to 18% in clinical trials, respectively, which is close to 

diversity representation figures in the US

Miller mentioned several challenges to enrolling diverse patient populations, including socioeconomic factors (i.e., education, culture, age, and race/ethnicity), awareness factors (i.e., health literacy), opportunity (i.e., geography and poor dissemination of information, and various communication methods), and decision factors (i.e., lacking trust in the industry and investigators, and negative preconceived notions about research). Janssen included diversity elements in feasibility assessments and segmented sites into diversity enrollment categories to overcome these challenges. However, selecting sites that can enroll diverse patients is not enough; hence, Janssen implemented educational programs, such as investigator meeting workshops, training materials, and highlighting diversity in study communications.

Moreover, other recruitment initiatives included targeted social media campaigns, local community outreach, and advocacy group outreach. Additional diversity inclusion strategies included easing the socioeconomic burden by offering patients door-to-door car service and meal stipends. These strategies contributed towards improving diversity inclusion in Janssen’s clinical trial programs.

The pandemic has unleashed demand offered by eClinical technologies that support decentralized clinical trial conduct to 

expand diversity inclusion in hard-to-reach communities

. Amidst this unprecedented demand, the clinical trials industry is known to resist novel eClinical technologies and methodologies to innovate. Accordingly, Ken Getz, Professor, and Director of Tufts CSDD, aimed to answer that question by discussing preliminary study results on the innovation process and opportunities to optimize drug development operations. This study aimed to “

characterize and measure primary process and mechanisms that sponsors use in adopting innovations supporting clinical development operations and to identify best practices and shortcomings

.” Preliminary results indicate that economic risk, regulatory risk, lack of trust in solutions, and lack of commitment contributed towards adoption barriers. The study showed a straightforward four-step process towards new technology adoption (mainly by the biopharmaceutical industry and CROs), which includes the initiation phase (i.e., identifying a need, gauging interest and initial planning), the evaluation phase (assessing and piloting), the adoption decision phase (deciding whether to adopt the technology enterprise-wide), and the full implementation phase (i.e., broad rollout, communication, and training).

This process, however, does not appear to be fast enough for respondents, as 83% believe that their company took ‘somewhat’ or ‘much longer’ to adopt an innovation compared to their peers fully, and 58% believe that their enterprise is ‘late to adopt’ or ‘last to adopt.’ The most significant challenges towards innovation are in the later phases of the process, including the adoption decision and full implementation phases. To elaborate, challenges in the adoption decision phase include insufficient evidence, inability to determine ROI, and vendor/solution uncertainty and volatility; alternatively, contributing factors included quantitative evidence, internal champions, regulatory clarity, and senior management support. In the full implementation phase, major challenges included cross-functional buy-in and support, poor commitment, economic continuity, and lack of senior management support; on the other hand, contributing factors included change management planning, communication and promotion, visible senior management participation, and training and incentive alignment.

Interesting insights that may hinder innovation appeared to be culturally related, as 42% of respondents indicated ‘high’ to ‘moderate’ risk in poor performance reviews when pursuing adoption of new solutions, and 57% mentioned that adoption interferes ‘somewhat’ or ‘greatly’ with their current tasks and project deliverables. Nonetheless, 54% of respondents who rated their enterprise as ‘excellent’ at innovation adoption indicated they were rewarded for taking on innovation initiatives.

Real-world evidence, data analytics and AI in clinical trials

Real-World Evidence (RWE), data analytics, and AI was also a topic of discussion at DPHARM, as these topics go hand-in-hand with patient centricity and engagement. Jessica Scott, Head of R&D Patient Engagement at Takeda, and Wendy Sanhai, Specialist Leader at Deloitte, discussed patient experience data (PED) trends in clinical development. There was discussion on regulatory trends with PED; for example, the ICH in 2020 recommends global harmonization in patient inclusion perspectives, and FDA suggested more consistency in patient and caregiver input to inform regulatory decision-making. Asian agencies are also focusing on patient involvement in drug development. As defined by FDA, PEDs contain information that captures patients’ experiences, perspectives, needs, and priorities, including symptoms, impact, treatment experiences, input on study outcomes, preferences, and relative importance of issues. Patient engagement examples include symptoms, the burden of disease, and treatment, to name a few. Sanhai and Scott emphasized that since many regulators across the globe are mandating the use of PEDs, it is vital to increase awareness for PED use within the biopharmaceutical enterprise, and recommended identifying appropriate programs, inviting collaboration both internally and with regulators and patient organizations, and leverage various types of PEDs (i.e., Clinical Outcomes Assessments (COA), Patient-Reported Outcomes (PROs), and qualitative PEDs, such as interviews with patients and caregivers).

Earl Seltzer, Sr. Director of Global Feasibility at Labcorp, discussed how AI and data analytics play a key role in creating better patient experiences through RWE analysis. Seltzer suggested that billions of lab test results in Labcorp’s databases allow for individual and longitudinal data analysis, which can be done with AI and predictive analytics. For example, Labcorp now can predict NASH and use this predictive model to identify and potentially contact patients or their caregivers for health screenings and introduce them to research.

In summary, diversity inclusion, technology adoption, and RWE research were all topics that were linked to patient-centricity at DPHARM 2021. Diversity inclusion has been a regulatory recommendation for several years, and the biopharmaceutical industry is making strides in enhancing diversity in clinical trials via recruitment and site selection strategies, though data on diverse patient populations collected in clinical research is still not large enough to decipher statistical results. In addition, new insights on technology adoption resistance are emerging, and it appears the biopharmaceutical industry can improve and standardize its approaches towards adopting innovation more rapidly. Finally, RWE data collection and analysis are increasing in interest as regulatory authorities are expecting some form of PDEs in submissions, and the increasing availability of data allows for emerging disease prediction and early patient and caregiver clinical trial engagement opportunities.

, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials.

The main themes discussed at DPHARM 2021.

Industry Update: Highlights from DPHARM 2021

Decentralized Clinical Trials (DCTs) have taken the main stage in the clinical trials industry, which was significantly facilitated during the pandemic. However, similar to the initiation of risk-based monitoring (RBM), the concept of DCTs is at an infancy stage, and many enterprises are competing to make their mark in the field. This prompted the formation of the 

Decentralized Trials & Research Alliance (DTRA)

 to help better define and advance DCTs. In this article, Dave Hanaman, Co-founder of Curavit, will discuss his perspectives on DCTs.

Moe Alsumidaie: What is a Virtual CRO (VCRO)?

 Co-founder Joel Morse and I conceived the company from our experience at C3i, where we spent 20 years at the intersection of digital technologies and clinical research. We saw this space evolving for years and wanted to disrupt research by positively applying technology in new ways. So we launched Curavit officially in November 2019 and became the first virtual CRO—a contract research organization dedicated exclusively to designing and executing decentralized clinical trials.

As a VCRO, Curavit runs fully decentralized trials from start to finish and acts as a virtual site, managing the decentralized components of a hybrid clinical trial. We leverage industry-leading digital technologies, devices, and our cloud-based DCT platform to centrally capture, aggregate, manage, and analyze trial data for sponsors. Curavit also brings specialized therapeutic expertise for decentralized trials to ensure the most proficient minds and the best technologies are applied to every research study.

What are some of the benefits and the challenges associated with implementing decentralized clinical trials? Long term, will sites still be involved in research at all?

 One of the challenges is standardizing our vocabulary and aligning the industry on a collective understanding and definition of decentralized trials. From the vocabulary standpoint, we need to get on the same page, understand what works and what doesn’t work, and share ideas to work more collaboratively in this new digital world. I think organizations like DTRA help in that respect, and the media can help, but it is an evolution to get the industry to agree on definitions about what this is and what it isn’t.

There is also a lot of hype—often well-founded and well-intentioned. Still, it sometimes results in organizations trying to shoehorn technology into traditional trials and then call them decentralized.

When COVID caused many trials to be shelved, there were desperate and courageous efforts to rescue them. Sponsors did some things that made sense and some things that didn’t. I think the challenge is to understand what is realistic now, and soon. At Curavit, we design virtual trials from first principles – meaning, we work with sponsors and investigators upstream. These are professionals who understand IoT, wearables, digital technologies, remote data capture, and how to design digitally native trials. We focus on the elements of a trial that can be done well, using tech and work at the earliest stages to design protocols where innovative technology is integral to success and not an add-on.

Are DCTs at a stage where there is a clear definition of what they are, or are we still in the early stages?

 The simplest definition is: if you’re applying digital technologies to replace traditional face-to-face or bricks-and-mortar interactions, then you’ve designed a decentralized trial. The middle ground is less understood – the so-called hybrid trial that includes a mix of both in-person and virtual components of research.

We talk a lot about trials being entirely virtual or decentralized – and we have done some of these, but overall they still represent a small fraction of all trials – less than 5%. Before COVID, leaders predicted that 10-20% of trials would be fully decentralized in 10 years. I think that’s still a good prediction. COVID forced early adoption and created some premature hype, but significantly increased the acceptance of these processes and technologies. So, I believe DCT adoption will be considerably higher than predicted.

Some therapeutic areas are more challenging to decentralize. Even so, there are aspects of nearly every trial that could benefit from virtual technologies, even oncology. The growing middle of the bell curve for the foreseeable future is going to be hybrid trials. People have been working on this for 20+ years, but I think we’re finally getting to the point where DCTs are accepted, even embraced whenever possible.

It was the right idea at the wrong time then, but now it’s the right idea at the right time?

 Yes, and the technology is catching up to the vision. In 2007, Veeva introduced cloud-based CRM to an industry desperate for lower-cost technology models because so many major brand-name blockbuster drugs were coming off patent. Veeva’s well-touted success is an example of the right solution at the right time. Decentralized trials are similarly destined, supported by developments in IoT, wearables, and big data. People have been working to make DCT a reality for years, but the technology is finally maturing and readily available while the industry is calling for a greater focus on patients and access to trials for all. So once again, we have a case of the right solution at the right time.

Are there concerns around data privacy and what precautions is Curavit taking to protect it, especially now where the U.S. and many Western nations are under attack by foreign hackers. What can be done to address those concerns using a DCT model for research?

 From banking to life sciences, every industry is extremely concerned about protecting data. As in most things, there are tradeoffs. Decentralized trials that do not involve sites can be an advantage in limiting data risk. DCTs can be much more secure in many ways because you can centralize data in very safe, modern cloud systems. That is what Curavit is doing.

Curavit’s platform has been purpose-built for decentralized trials with proven, industry-leading software. HIPAA compliance and validation are built into the individual tools as well as the overall platform. No corners were cut in terms of applying modern cyber defenses.

Part of Curavit’s vision is to make research more accessible across all the demographics. How are you expanding clinical trials to those demographics through DCTs?

 First, DCT technologies and processes are fundamentally more suited to reaching previously underserved or underrepresented patient populations. It’s easier to expose more people to the opportunity to participate in research across social media, digital communities, and websites supporting specific diseases or conditions.

Second, and more specifically, DCTs leverage community-based outreach. For example, we partner with Clinispan out of North Carolina whose purpose is to recruit underserved populations. Par 80 in Boston partners with community health centers serving minority populations. These efforts reach out to minority populations to include those who distrust or have not been previously exposed to research.

Third, we have had ongoing discussions with a global pharmaceutical company interested in Native American populations that embody two distinct underserved groups: indigenous and rural populations.

Where do you see DCTs going in the next ten years?

 Optimistically, in 10 years, we won’t think of DCTs as unusual because the technologies and processes will be commonplace. DCTs won’t be any more novel than computerized businesses are today.

Most data capture will be in the cloud a decade from now, and DCTs will enable a more burdenless patient research experience. To clarify, that doesn’t mean face-to-face interactions with physicians will go away. Even in complex therapeutic areas like oncology, there’s plenty of opportunities to use digital technologies to gather new data and reduce patient burden. We won’t think of DCTs as a distinct subset. In 2031, DCTs will have disrupted clinical research in profound ways that are better for all patients, better for all sponsors, and ultimately better for public health.

Dave Hanaman, Co-founder of Curavit, discusses his perspectives on decentralized clinical trials.

Insights into Definining Decentralized Clinical Trials

In its ongoing campaign to encourage industry adoption of more efficient and reliable pharmaceutical production methods, FDA is expanding its Emerging Technology Program (ETP) and providing more support for new drug applications (NDAs) that present advanced manufacturing technologies. While these initiatives aim to limit drug shortages and recalls due to quality issues, the program also seeks to expand investment in domestic production to enhance access to critical therapies and vaccines for patients in the United States. At the same time, the agency is collaborating with foreign regulatory authorities to support international harmonization of policies designed to advance continuous manufacturing operations for drugs and biotech therapies around the world.

The challenges of meeting urgent demands for more new medical products during the COVID-19 pandemic has highlighted the value of more responsive and flexible manufacturing methods, including manufacturing systems that can be scaled up more quickly and automated processes that can reduce in-plant staff and permit more flexible employee work schedules. These developments have increased collaboration and partnering among biopharma manufacturers over the past 18 months, as competitors have worked together to accelerate access to needed therapies by providing fill/finish services for vaccine makers and APIs for finished dosage forms, among other joint efforts.

These issues and opportunities will be discussed at an FDA conference on innovations in pharmaceutical manufacturing, as outlined 

 on the topic issued in March 2021 by the National Academy of Sciences, Engineering and Medicine (NASEM). This review requested by for the Center for Drug Evaluation and Research (CDER) of the importance and challenges for advancing innovative biopharmaceutical manufacturing aims to reduce quality-related shortages that can limit patient access to safe and effective drugs. The virtual meeting on Oct. 28 and 29, 2021 will discuss industry advances in manufacturing systems and policies and actions for moving forward.

CDER support for these initiatives appears to be having an impact, according to in a recent 

. CDER Director Patrizia Cavazzoni and Michael Kopcha, director of CDER’s Office of Pharmaceutical Quality (OPQ), note that the agency approved its first application for a drug produced by continuous manufacturing in 2015 and 10 more applications since then that utilize advanced approaches for finished dosage forms, APIs, and biological molecules. Now more than 100 proposals utilizing a range of innovative technologies have been presented to agency officials, necessitating an expansion in the ETP program to handle the workload.

FDA’s advanced manufacturing initiative also aims to enhance the competitiveness of US firms in the global pharmaceutical market by lowering costs and promoting quality. Acting Commissioner Janet Woodcock cites visible success in this area in a tweet posted Oct. 15, 2021, reporting that more than 80% of the drugs made using advanced manufacturing technologies are produced domestically. An FDA Center for Advancement of Manufacturing Pharmaceuticals and Biopharmaceuticals established in June 2021 is coordinating analysis related to such topics as end-to-end continuous manufacturing, portable and modular distributed manufacturing platforms, and use of artificial intelligence or advanced modeling approaches in manufacturing.

At the same time, FDA is promoting international coordination and agreement on the scientific issues and regulatory policies related to implementing and overseeing modern drug manufacturing, as seen in the 

 developed through the International Council for Harmonisation (ICH). FDA recently posted the initial version of this standard for Continuous Manufacturing of Drug Substances and Drug Products, which applies to new drugs, generics, therapeutic proteins, and biosimilars. Manufacturers and other stakeholders should submit comments on the draft document to FDA by Dec. 13, 2021.

This ICH initiative aims to advance biopharmaceutical quality through operations that reduce manual handling that leads to human error, utilize online monitoring and controls, increase manufacturing speed and efficiency, and install smaller equipment that cuts costs.Ultimately advanced manufacturing systems would enable firms to respond “more nimbly” in the event of drug shortages and to adopt tailored systems that fit the needs of precision medicine.

Yet, FDA and industry face key challenges in advancing these initiatives. The agency’s traditional focus on ensuring the safety and efficacy of novel therapies has discouraged manufacturers from adopting less traditional production processes, especially when the evaluation of advanced manufacturing systems in an NDA might complicate or delay market approval. To move forward in this area, the NASEM report points out that FDA needs a program for evaluating innovative manufacturing processes and mechanisms outside the traditional NDA process, along with flexible and efficient procedures for processing post-approval changes to advance modern manufacturing methods for approved products. CDER leaders note that Congress has provided important funding to support advanced manufacturing, but that the agency will require added expertise and resources to progress further in building its capacity for assessing multiple novel technologies.

FDA is expanding its Emerging Technology Program and providing more support for new drug applications that present advanced manufacturing technologies.

Featured Content

Applied Clinical Trials October 2021

The Evolution of Site Selection