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Applied Clinical Trials September 2021

Clinical research is radically changing as more and more trial sponsors embrace a decentralized model to solve two fundamental challenges: addressing barriers to clinical trial accessibility and improving diversity amongst clinical trial participants.

At least half of FDA trials in the US are conducted in only 1-2% of zip codes. Low participation in clinical trials remains an issue across research, with less than 5% of the global population participating. In addition, 

85% of clinical trials fail to meet their enrollment targets

, which is more than three times the number of 

 Of the trials that achieve their enrollment targets, a lack of diversity due to accessibility remains a big issue. If the current clinical research process doesn’t adapt to these changing population demographics, the life sciences industry will continue developing drugs and devices that are only shown to work for a select few, leaving out the rest.

The access to novel clinical trial digital tools creates opportunities for patient diversity in research. As a result, we see a shift from site-centered to patient-centered research, as the industry is proactively engaging with patients in a way that better fits their needs, according to Dr. MaryAnne Rizk, Medable’s Chief Strategy Officer. The goal, says Rizk, is to ensure that we are actively capturing the voice of patients so we create better treatments for everybody. In this interview, Rizk discusses how this shift will manifest in real life.

Should all drug development be patient-centric? What are the biggest challenges in clinical research today hindering patient-centricity?

 I believe decentralized research is the path to all-inclusive medicine for the broader patient population. We get there by creating a more convenient journey for patients that empowers the flexibility of choice for clinical care as an option that is either remote or a hybrid. Medable’s CEO is a practicing physician and brings a fresh perspective with her medical lens to how we reshape patient engagement, affording us a rare opportunity to put technologies in the hands of patients so we can learn what works best for their needs and drive the best results for more all-inclusive treatments.

However, one challenge standing in the way is learning how to evolve the site of the future. We believe sites are fundamental to patient experiences, so we want to enhance their essential role through technology, not replace sites with technology. The future is a hybrid. Some patients will want to engage remotely as much as possible, and others may prefer to do some visits at a local site and some remotely and just one or two at the primary site. In other words, tomorrow’s research site may not look the same as it does today. For instance, it might be a retail pharmacy or community clinic with a central site coordinating care and leveraging advanced technology. Medable is helping to reduce the patient and clinician burden and capture better data by digitizing as much of the research process as sensible.

Data capture is another challenge—and a significant opportunity to capture critical insights from study visits. Thanks to the decentralization of trials, we have a proliferation of data collected earlier and more often from various sources. There are inherent challenges with the sheer quantity and variety of data today. But Medable is driving a radical movement to be closer to patients, modernize sites, and establish a concierge-like service—a consumer-grade experience for patients that makes data insights easier to capture. When we collect patient data before, during, and after a study, we can partner with sponsors on the meaningful use of that data.

MA: How do you aim to increase DCT adoption in the clinical trials industry?

 Medable has engaged over one million patients across a myriad of over 5,000 sites globally, operating in 40 countries across 60 languages—it’s a significant start. With the broad expansion of reaching more patients and sites globally, we are advancing the capabilities to make an impact. A flexibly decentralized model needs to enable greater patient access while providing a flexible and seamless experience across all users that improves trial operations and time to treatment. 

For example, Medable empowered one precision medicine company to develop new therapies for a rare disease screening of age-related macular degeneration that required a deeper understanding of the disease and cost-effectively screening of 11,000 patients. Our decentralized platform model and direct-to-patient shipment workflow drove a 50% reduction in patient enrollment time and a 75% reduction in study sites, resulting in a $20M decrease in trial costs to achieve the study’s endpoints.

Moving forward, the way to continue to expand the DCT adoption is to design technology solutions that are agile, simple, and elegant—employing human-centered design. A good design is visible, but an exceptional design is invisible. As an example, we’re now seeing improved intelligence to optimize the enrollment period and study startup. We’re getting feedback, not just after a trial but throughout the cycles of a clinical setup. This is important as we’re looking to optimize how we approach our sites, creating programs like our Site Network Council that give us valuable insights to optimize the way they work and create the highest value. To do this, we are creating executive leadership teams at Medable that bring together a rich pedigree of scientific, medical, technology, and design backgrounds to advance how research is conducted from a remote setting.

Second, engaging directly with patients is crucial, and Medable is doing this by nurturing collaborative networks with patient advocacy groups and physicians. Consider the consenting process. Medable’s consent tool ensures patients understand what they’re going to be signing up for, which is critical because the most informed patient is the most engaged patient. As a result, we see up to 90% patient satisfaction.

Lastly, it is critical to up-skill the talent needed for the next generation of the resources necessary to modernize clinical trials. What will a digital CRA or a digital analyst, or an architect look like in a few years? What are some of the things they need to think about when using data, digital technologies, and accommodating patient engagement? The industry should be motivated to champion leaders who will help advance the mission because no one can do it alone. We want to create an ecosystem of partners, sites, patients, sponsors, and CROs motivated to expedite faster treatments.



MA: Will DCTs bridge the racial and economic divides in clinical research? Can you tell me why or why not?

 DCTs are changing the future of research. And the two leading critical success factors in terms of the impact of radically advancing clinical research are access and diversity. The convenience of accessing clinical trials within your iOS devices or mobile devices opens us to a world of ubiquitous access—and this is naturally enabling more diverse data sets so that FDA-approved medicines will be as effective to ensure a diverse representation of people from varied economic and racial backgrounds; expanding clinical trial access to many more patients.

Also, today we see a new trend in patient-centered intelligent protocol design, boosted by a digitally focused mindset. The focus on diversity drives industry-wide change that includes widening the net with more access to care.

MA: Why are you passionate about human-centered research?

 Human-centered research is about putting the patients first and creating a consumer-grade experience for trial participants. Today we put the letter “E” in front of everything, right? E-consent, E-visit, etc. And because we’re moving through this digital age, you recognize that the patterns needed to improve and impact require understanding and predictive analytics.

If we’re able to advance the way we bring data and insights together, not only for clinical research but also, so patients have access to better care—that is why I’m wildly passionate about human-centered design. We recognize that the impact and the outcome are rich in terms of the unique advantage of improving health care through technologies and data tools.

You’ve worked on E-clinical systems at a range of established enterprises like Merck, IQVIA, and Oracle. So, what inspired you to join a growing company like Medable?

 Medable is on a mission to modernize clinical research for the benefit of patients. During the pandemic, I was given this opportunity to go where I could make the largest impact. And when I learned Medable’s vision is to redesign the way clinical trials should be conducted to focus on patients, it was in perfect alignment with my view. Medable wants to create the most intuitive patient experience and build on a true, cloud-based SaaS-enabled technology platform, matching my mission. This is the way to create the most significant impact, with ubiquitous access to care through the modernization of clinical trials. And when we think about what it takes to create this impact, it involves understanding the patient, generating a user community that’s going to provide input on their expectations to create predictive insights on what’s needed for clinical trials.

Additionally, Medable has put together a world-class team of leaders with rich domain expertise, whether you’re in operations, product management, technology, operations, clinical development, patient engagement, science, or compliance. It’s exciting for me to get the chance to work with such brilliant minds for collective drive impact forward.

My role is to find a unique way to develop novel innovation partnerships for a diversified ecosystem. I’m fully committed so that we can intelligently connect patients and sites to advance medical research.

, 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.

Articles

Dr. MaryAnne Rizk, Medable’s Chief Strategy Officer, discusses why sponsors are embracing the decentralized model more often and how it's solving issues like accessibility and diversity. 

On the Precipice of a Shift to Patient-Centricity in Clinical Research: How Will Technology Help?

Elligo Health Research has announced the acquisition of ClinEdge, which also includes GuideStar Research and BTC of New Bedford. The transaction of $135 million was funded through new co-lead investors Morgan Stanley Expansion Capital  and Ally Bridge, along with participation from Norwest Venture Partners and existing investors.

Perella Weinberg Partners served as financial advisor and Goodwin Procter LLP served as legal counsel to Elligo. Edgemont Partners served as exclusive financial advisor to ClinEdge.

Elligo Health Research Acquires ClinEdge 

There is increased interest in the provision of healthcare in a manner that is more convenient to the patient. The COVID-19 pandemic has further shifted this trend, driven by the need for social distancing precautions to avoid unnecessary personal contact and potential exposure to the virus. Virtual doctors’ visits and remote COVID-19 testing have now become commonplace.

 This shift towards patient-centricity in healthcare has accelerated telemedicine and at-home testing, bypassing the inconvenience of travel and time away from family, work, and school.

 These approaches use technology to build systems around the patient. We are in a unique moment, with an opportunity to rethink how healthcare is provided, to improve health outcomes by increasing accessibility and decreasing patient burden. Can we build upon what we have learned during the pandemic and develop patient-centric approaches across healthcare?

An important component for the provision of patient-centric healthcare is the ability to collect blood samples remotely in a manner that delivers samples of a quality comparable to that of current standard phlebotomy collection, enabling routine clinical testing, monitoring disease progression and testing drug concentrations.

 This blood sampling could be performed at the patient’s home, at a nearby pharmacy, or at a local clinic, rather than a centralized facility. There is a growing body of evidence to suggest that home-based phlebotomy will become increasingly common and is preferred by many patients over more traditional approaches involving centralized clinical facilities.

 The ability to collect a sample of blood without needing a phlebotomist can decrease patient burden and improve patient compliance, especially with scheduled sample collections.

Significant technological advancements in analytical science have enabled the use of very small blood sample volumes for quantitative testing. However, standard venipuncture approaches are still being practiced to collect several milliliters of venous blood, of which less than 10% is typically used for testing. These advancements are making the current logistical and procedural hurdles for patients more a function of habit and inertia, rather than medical necessity. Reducing the volume of blood collected is critical, particularly amongst vulnerable populations like oncology and pediatric patients.

 The possibility of reducing blood collection volumes in adults was proposed by Smoller in 1989, by employing pediatric-sized tubes.10 Since then, technological advancements have made the collection of reduced blood volumes a reality. Coupling convenient, routine blood sampling approaches with advanced highly sensitive analytical testing can provide high quality decisional data in a patient-centric manner.

The collection of a small volume of blood from a heel prick has been used for over 60 years for metabolic and genetic testing in newborns. More recently, this technology has advanced significantly, with commercially available devices that collect high quality blood samples from finger pricks or the upper arm for all age groups.

 Importantly, these sampling devices do not require a phlebotomist to be present. Instead, the sample can be self-collected, or with the assistance of a care giver and are designed to collect small volumes of blood of the same quality as professionally collected venous blood.

 Some of these techniques require a finger-prick using a lancet, followed by blood collection, while others are self-contained devices with a built-in incision and blood collection. Examples of commercially available devices include the Neoteryx Mitra,

 These devices are capable of collecting from as little as 20 microliters (approximately half a drop) to several hundred microliters of blood and have been widely used to determine clinical parameters,

 and more recently, COVID antibody levels.

 Some of these devices enable the collection of a fixed volume of blood, collected as dried blood, which can then be shipped and handled at room temperatures—avoiding the need for freezers and dry-ice for storing and shipping samples—enabling its adoption even in remote areas with limited infrastructure. Devices are also available for the collection of a small volume of wet blood from the upper arm which can then be separated as plasma or serum, similar to a standard venipuncture blood draw, thus providing the same liquid matrix for analysis (examples include Tasso SST and SeventhSense TAP II).

Patient-centric blood sampling techniques have been gaining popularity for use in pharmaceutical drug development; however, to date they have not been broadly accessible to the general public.

 This can be partially attributed to the “clinic-centric” healthcare model, where reimbursement is dependent on in-person visits and sample collection. Thus, the status quo remains and anyone who needs a blood test is required to go to the doctor’s office or clinic. However, recent experiences have demonstrated that these techniques can be widely implemented and that commercially available blood sampling devices are a perfect complement to the exponentially expanding space of telemedicine.

 It is apparent that improving patient convenience and the sampling experience, as well as enabling more frequent testing, can improve and expand monitoring of our “bodies” to know if everything is okay or react to issues early. Such information can empower the physician and patient to seek earlier intervention and evolve beyond reactive treatment, toward proactive disease prevention.

The cost of some of the technologies involved in this new paradigm may be higher than traditional blood collection approaches. However, studies have demonstrated that the overall cost to society will be lower, by improving health outcomes and allowing broader access and patient convenience.

 The availability and adoption of patient-centric approaches can provide access and treatment options to patients not geographically co-located with clinical sites and improving access in rural or lesser developed communities, globally, potentially improving general health of the population.

The responsibility for our collective health belongs to us all. The successful adoption and implementation of these blood sampling capabilities will require stakeholders to work together across organizational boundaries to deliver improved care. The benefits of implementing home blood sampling are clear; however, there are challenges for widespread adoption including training to ensure proper collection and processes for expedited return of the sample for analysis. Advances in mobile technologies for training, data capture (time/date stamp) and sample tracking, along with expanding home delivery and collection processes are expected to potentially alleviate this. We believe the learnings from the COVID pandemic will further drive innovation, including the ability to conveniently sample blood at home. This is a call for action for healthcare systems to make “patient-centric” blood sampling a reality to improve human health.

is a Researh Advisor for Lilly Research Laboratories, Eli Lilly and Company

is a Principal Scientist for Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck & Co, Inc.

is the Director of Spooner Bioanalytical Solutions Ltd.

Keesara, S.; Jonas, A.; Schulman, K., Covid-19 and Health Care's Digital Revolution. 

James, C. A.; Barfield, M. D.; Maass, K. F.; Patel, S. R.; Anderson, M. D., Will patient-centric sampling become the norm for clinical trials after COVID-19? 

Anderson, M., How the COVID-19 pandemic is changing clinical trial conduct and driving innovation in bioanalysis. 

PCSIG Patient Centric Sampling Interest Group. 

Mbughuni, M. M.; Stevens, M. A.; Langman, L. J.; Kudva, Y. C.; Sanchez, W.; Dean, P. G.; Jannetto, P. J., Volumetric Microsampling of Capillary Blood Spot vs Whole Blood Sampling for Therapeutic Drug Monitoring of Tacrolimus and Cyclosporin A: Accuracy and Patient Satisfaction. 

WHO Guidelines on Drawing Blood: Best Practices in Phlebotomy

Wickremsinhe, E. S., M.; Talkington, B.; West. L, DIY Blood Sampling for Pediatric Clinical Trials – The Patients Perspective. 

Sztefko, K.; Mamica, K.; Bugajska, J.; Maziarz, B.; Tomasik, P., [Blood volume for biochemistry determinations--laboratory needs and everyday practice]. 

Valentine, S. L.; Bateman, S. T., Identifying factors to minimize phlebotomy-induced blood loss in the pediatric intensive care unit. 

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Smoller, B. R.; Kruskall, M. S.; Horowitz, G. L., Reducing adult phlebotomy blood loss with the use of pediatric-sized blood collection tubes. 

Delahaye, L.; Veenhof, H.; Koch, B. C. P.; Alffenaar, J. C.; Linden, R.; Stove, C., Alternative Sampling Devices to Collect Dried Blood Microsamples: State-of-the-Art. 

Spooner, N.; Anderson, K. D.; Siple, J.; Wickremsinhe, E. R.; Xu, Y.; Lee, M., Microsampling: considerations for its use in pharmaceutical drug discovery and development. 

https://www.trajanscimed.com/pages/hemapen

https://hemaxis.com/products/hemaxis-db10/

https://www.drawbridgehealth.com/onedraw/

Crawford, M. L.; Collier, B. B.; Bradley, M. N.; Holland, P. L.; Shuford, C. M.; Grant, R. P., Empiricism in Microsampling: Utilizing a Novel Lateral Flow Device and Intrinsic Normalization to Provide Accurate and Precise Clinical Analysis from a Finger Stick. 

Roadcap, B.; Hussain, A.; Dreyer, D.; Carter, K.; Dube, N.; Xu, Y.; Anderson, M.; Berthier, E.; Vazvaei, F.; Bateman, K.; Woolf, E., Clinical application of volumetric absorptive microsampling to the gefapixant development program. 

Delahaye, L.; Stove, C., Alternative Sampling Strategies in Therapeutic Drug Monitoring: Microsampling Growing Toward Maturity. 

NIAID SARS-COV2 Pandemic Serosurvey and Blood Sampling. 

https://clinicaltrials.gov/ct2/show/NCT04334954

Klumpp-Thomas, C.; Kalish, H.; Drew, M.; Hunsberger, S.; Snead, K.; Fay, M. P.; Mehalko, J.; Shunmugavel, A.; Wall, V.; Frank, P.; Denson, J. P.; Hong, M.; Gulten, G.; Messing, S.; Hicks, J.; Michael, S.; Gillette, W.; Hall, M. D.; Memoli, M. J.; Esposito, D.; Sadtler, K., Standardization of ELISA protocols for serosurveys of the SARS-CoV-2 pandemic using clinical and at-home blood sampling. 

Spooner, N.; Anderson, M.; Wickremsinhe, E. R., Patient-centric sampling special focus issue. 

Martial, L. C.; Aarnoutse, R. E.; Schreuder, M. F.; Henriet, S. S.; Bruggemann, R. J.; Joore, M. A., Cost Evaluation of Dried Blood Spot Home Sampling as Compared to Conventional Sampling for Therapeutic Drug Monitoring in Children. 

This article sets out a vision of adopting convenient alternative blood sampling approaches that places the needs of the patient at the center and enables active monitoring, before the onset of clinical events, leading to improved healthcare.

Opportunities for Improving Clinical Decisions with Patient Centric Remote Blood Sampling Approaches

Futura Medical has partnered with OCT Clinical to run its FM71 clinical study for MED3000 in erectile dysfunction in four countries: Bulgaria, Poland, Georgia, and the USA. The companies have already reported the first patient entering the screening in Georgia earlier this week.

MED3000, is a topical gel developed specifically for the treatment of erectile dysfunction ("ED"). It is a fast-acting topical treatment which has the potential to be a highly differentiated product by addressing significant unmet needs in the ED market including speed of onset, safety, and tolerability.

The OCT Clinical team has already obtained study approval in Georgia where site initiation has been started: 50% of sites have been opened and the first patients have been screened.

As soon as the clinical trial application approvals are obtained from the regulatory authorities in Bulgaria, Poland, and the USA the CRO will start site initiation in these countries. For this project, the OCT Clinical team will engage the total of 18 research sites.

This is a multi-center, randomized, open-label, home use, parallel group, clinical investigation of topically-applied MED3000 gel and oral tadalafil tablets for the treatment of erectile dysfunction (ED) over a 24-week period. This clinical investigation is intended to assess the efficacy and safety of MED3000 gel in 100 male patients clinically diagnosed with a mix of mild, moderate, and severe ED. The enrollment target will include 20 African American patients (from the US) and 80 patients from Eastern Europe, who will undergo a seven-month study.

Futura Medical Partners with OCT Clinical to Run FM71 Study

MMS Holdings Inc. (MMS) has announced the release of SmartStart Tech-Enabled Templates that aim to reduce time and effort in the document content creation process while increasing the quality of deliverables.

SmartStart Templates apply structured authoring rules to the authoring process and include tech-enabled templates for protocols, statistical analysis plans (SAPs), and clinical study reports (CSRs). These templates were developed to allow for the reuse of data across deliverables, such as protocol to protocol, protocol to CSR, protocol to SAP, CSR to CSR, and SAP to SAP.

Key features of SmartStart templates are proven to reduce human errors by:

Automatically sharing reusable content within and across protocols, SAPs, and CSRs

Reusable content in the body of the protocol and CSR will automatically update in the synopsis

Reusable content can be imported between documents

Presenting reusable content across products, programs, and therapeutic areas

MMS SmartStart Solution Aims to Ease Document Content Creation Process

Raj Indupuri, CEO of eClinical Solutions, talks about the build vs. buy pendulum faced by CROs, the pros and cons of each model, and more.

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Clinical Trials Solutions: Build vs Buy

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If the debate has been heated over vaccines for adults and on the need for extra booster shots, FDA and its expert advisors will face even more scrutiny over the safety and value of vaccinating children under age 12. This population generally has had much lower COVID-19 infection rates than adults, but hospitalizations now have increased dramatically with the spread of the Delta variant, plus the return to school and other activities. The rise in pediatric COVID cases has alarmed the medical community, yet widespread vaccine hesitancy among many parents will make it critical to present strong safety results to gain broad protection for children.

The issue has moved to center stage as Pfizer/BioNTech announced plans to seek FDA approval this month of a smaller dose of its Comirnaty vaccine for children ages five-11, as well as similar approval from the European Medicines Agency and other regulatory authorities. As Pfizer did in expanding use of its vaccine to younger adolescents, the company will file an emergency use application (EUA) with FDA, based on results from a Phase II/III study of a two-dose regimen on over 4000 participants aged six months to 11 years.

 The study shows, according to Pfizer, that a lower 10-microgram shot for the five-to-11 age group, one-third the dose for adults and adolescents, provides a sufficiently robust neutralizing antibody response, while also supporting safety and tolerability in these young subjects.

The clinical trial also enrolled similar numbers of younger children ages 6 months to five years and hopes to provide topline readouts for this group by year-end. Children under age five received a lower three microgram dose for each of two injections, and results will be evaluated for two age cohorts, children two-five years of age and those six months to two years old.

This initial Pfizer/BioNTech statement did not present specific study data, but sponsor said it will submit its research results for publication in a scientific peer-reviewed journal, while also preparing its filing for FDA. The announcement specified that clinical trials in multiple regions enrolled 2,268 children ages five-11, with one-third receiving placebo. However, due to the generally lower infection rate among youngsters, there were too few numbers of ill participants to determine higher protection from the vaccine vs. placebo; that conclusion is based on a comparison of higher immune response levels in vaccinated vs. unvaccinated study participants.

The sponsor also notes that the lower dose for children can be linked to fewer side effects. In an early study that administered higher doses to young participants, adverse events were higher, although still comparable to older patients. But those children who received the lower dose experienced fewer incidences of fever, headache and fatigue, while also showing a strong antibody response. Even after increasing the size of the pediatric trial at FDA’s request, Pfizer found no cases of heart inflammation or other serious side effects that have occurred after vaccination with some older individuals, although the sponsors continue to monitor study participants for ongoing effects.

FDA staff will review the Pfizer data closely following its submission and is expected to ask its Vaccine and Related Biological Products Advisory Committee (VRPBAC) to weigh the results and make recommendations. If approved, the Advisory Committee on Immunization Policy (ACIP) at the Centers for Disease Control and Prevention (CDC) then will propose a specific vaccination schedule.

In response to earlier pressure from some quarters for FDA to quickly authorize preventives for younger children, agency leaders explained the need for very careful scientific evaluation to ensure that any vaccines for children are safe, as well as effective. FDA acting commissioner Janet Woodcock and Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), penned a statement in early September emphasizing that FDA “will follow the science” to fully assess the safety of current vaccines. Woodcock and Marks also warned parents not to pressure pediatricians to provide their children with a vaccine approved for adults and adolescents:as far as vaccines go, children are not just young adults.

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-positive-topline-result

https://content.govdelivery.com/accounts/USFDA/bulletins/2f09162

If the debate over vaccines for adults and the need for extra booster shots has been heated, FDA will face even more scrutiny over the safety and value of vaccinating children under age 12.

The Next Big COVID Challenge: Vaccines for Children Under 12

Amid political pressures and dissension on multiple fronts, FDA and its panel of vaccine experts weighed the evidence and worked to ensure a science-based decision on whether to authorize additional shots of Pfizer’s COVID-19 preventive to further protect those already receiving recommended doses. The day-long meeting Sept. 17, 2021 of FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC)

 concluded with the panel recommending that a third dose of the Pfizer/BioNTech Comirnaty vaccine be authorized only for patients over age 65, plus those at high risk of infection related to occupation, such as health care workers and teachers.

A formal recommendation from FDA on the Pfizer booster, likely to be issued today, will be considered this week by the Advisory Committee on Immunization Policy (ACIP) at the Centers for Disease Control & Prevention (DCD). That panel will advise practitioners and health agencies on when and where to administer any additional shots in ongoing efforts to curb the COVID-19 pandemic.

The FDA advisors agreed unanimously on the more limited booster plan after soundly rejecting Pfizer’s original request to authorize its third shot for everyone over age 16, as covered by the BLA for the vaccine recently approved recently by FDA’s Center for Biologics Evaluation and Research (CBER). The panel felt there was insufficient data to support more widespread administration, and that boosters could pose added risks for men under age 40, who have experienced rare cases of myocarditis following vaccination. A main point of discussion was whether waning immunity from the initial two-dose vaccine regimen was due to effects of the Delta variant or to limitations of the Pfizer vaccine itself. Pfizer researchers published a letter in Sept. 15 the 

 summarizing its research to support a booster dose,

 but that failed to convince the advisory panel of the need for widespread third shots.

The debate over the issue was intensified by the recent announcement of pending departures of leading FDA officials who had expressed dismay over earlier statements by President Biden backing booster shots in the U.S. while FDA was examining the issue. Marion Gruber, long time director of CBER’s Office of Vaccine Research & Review (OVRR), and OVRR deputy director Phillip Krause announced last month that they would both retire from FDA after many years of service, most recently shepherding through speedy emergency approvals for effective anti-COVID vaccines.

In addition, Gruber and Krause were prominent co-authors of a leading article published in The Lancet questioning booster shots while much of the world still awaited initial COVID vaccines.

 The article by a group of vaccine scientists formed by the World Health Organization (WHO) argues that much uncertainty remains about the timing and value of extra shots, and that boosters for healthy adults should be delayed until at least 40% of the global population is vaccinated.

The debate within the Biden administration and FDA opened the door to widespread criticism and questioning of the booster shot policy. Leading House Republicans charged FDA officials with caving to White House pressure to speed access to booster shots and demanded that FDA commissioner Janet Woodcock provide them with all documents related to the study and implementation of a booster shot option plus communications between the agency and the White House on thisissue.

While the politicians look to make points over the policy debate, the VRBAC panel weighed the scientific evidence presented at the Sept. 17 session. That included current data on COVID-19 prevalence, infection and hospitalization rates from the Centers for Disease Control and Prevention (CDC) and from the United Kingdom. Of particular interest was a report on how a recent Pfizer vaccine booster program in Israel reduced infection rates and hospitalizations. Pfizer presented its own analysis on how protection from Comirnaty waned over six months after initial doses and how boosters could provide important added protection. But the advisors found the Israeli and Pfizer data too limited and unconvincing to approve boosters for the entire U.S. population. The narrower recommendation to add shots for the elderly and immune-compromised is seen as a compromise to provide protection where most needed while sponsors gain added information.

A main issue for the international health research community still is whether still limited supplies of effective preventives should be provided to those already protected by authorized shots, while vaccines remain severely limited in many in regions of the world. The advisory panel did not address that question directly, and ample vaccine supplies in the U.S. appeared to offset the issue.

Members of the advisory panel and experts from CDC and FDA did agree that more widespread vaccination of the American public would do more to prevent high COVID infection rates than booster shots for those already benefiting from protection. However, that possibility was further countered by the ranting of vaccine opponents about the safety and value of any COVID preventive, as heard in multiple presentations during the usual one-hour public comment period at the VRBAC meeting.

The debate will continue, as Moderna has announced it also will seek FDA approval of a third shot to its two-dose vaccine regimen, citing similar waning of antibodies six months after the second shot and no added safety concerns. Perhaps Moderna will consider closely the recent debate and target its booster plan to the higher-risk population, as recommended by the advisory panel for the Pfizer preventive.

https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-september-17-2021-meeting-announcement#event-information

https://www.nejm.org/doi/full/10.1056/NEJMc2113468?query=TOC&cid=NEJM+eToc%2C+September+16%2C+2021+DM295772_NEJM_Non_Subscriber&bid=617019028

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02046-8/fulltext

https://www.republicanwhip.gov/wp-content/uploads/2021/09/Letter-to-FDA-on-Political-Interference.pdf

FDA’s Vaccines and Related Biological Products Advisory Committee announces its recommendations for the authorization of a third dose of the Pfizer/BioNTech Comirnaty vaccine.

Vaccine Booster Battle Reveals Rifts Among Regulators, Sponsors

WCG today announced the expansion of WCG Avoca Quality Consortium (AQC), a forum dedicated to improving clinical trials via the development of standardized performance metrics and knowledge sharing that drives cross-industry collaboration. WCG AQC brings together WCG Metrics Champion Consortium (MCC) and AQC, creating an organization uniquely positioned to drive the adoption of quality management and compliance best practices across the global clinical trials industry.

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Applied Clinical Trials September 2021