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Applied Clinical Trials April 2021

Dermatology clinical research is evolving rapidly in response to a regulatory landscape that favors clinical trials that are safer, more justifiable, and less burdensome to study participants. Putting the patient at the center of every phase of the research process—from discovery and preclinical testing to clinical trials and post-marketing studies—can help accelerate the path to successful commercialization.

In this article, we explore how a strategic patient-focused approach to planning and implementing dermatology clinical trials can help to bring new therapies to market.

Skin diseases are the fourth leading cause of health afflictions, affecting nearly 900 million people worldwide.

 Despite advances in our understanding of the etiology, epidemiology, and pathophysiology of dermatologic conditions, much of the development progress has been in a small subset of diseases with multiple approved therapies, including skin infections, psoriasis, atopic dermatitis, acne, rosacea, melanoma, and actinic keratosis.

In recent years, there has been a dramatic increase in dermatology drug development activity for conditions such as atopic dermatitis, psoriasis, and melanoma, with hundreds of clinical trials currently underway or in the planning stages. For the majority of the more than 3,000 common and rare skin diseases, however, the need for safe and effective treatments remains largely unaddressed—but there is evidence that this trend could be changing.

For instance, the number of drugs approved for rare skin diseases has risen over the past ten years, particularly for skin-related cancers followed by genodermatoses (see Figure 1).

 Research activity has also been bustling, with a variety of development programs involving innovative, targeted therapies.

Figure 1. Orphan drugs for skin conditions and skin-related cancers

Adapted from Karas L, et al. J Am Acad Dermatol. 2019;867-877.

With a patient-focused approach, a drug or device is designed to address specific patient characteristics and needs. Involving dermatology patients—and their families—in the research and development process optimizes both the likelihood of study success and the probability of market adoption. It is also necessary for meeting the expectations of regulators, providers, and payers.

In June 2020, the FDA announced the development of a series of guidance documents that address how stakeholders can collect and submit patient experience data and other relevant information from patients and caregivers as part of the product development and regulatory decision-making process.

Collecting Comprehensive and Representative Input

, published in June 2020, which discusses sampling methods that could be used when collecting patient input

Methods to Identify What is Important to Patients

, available as a draft guidance, which explores methods for gathering information about issues that are important to patients and offers best practices for performing unbiased qualitative research

Guidance 3: Selecting, Developing or Modifying Fit-for-Purpose Clinical Outcomes Assessment

,forthcoming, which will address the development of potential study instruments

Guidance 4: Incorporating Clinical Outcome Assessments into Endpoints for Regulatory Decision Making

, forthcoming, which will discuss approaches, standards, and technologies for collecting and analyzing clinical outcome assessment data to drive regulatory decision making.

Additionally, the European Medicine Agency is working on ensuring that the patient voice is systematically incorporated throughout drug development

Providers value the patient perspective because they rely on not only published clinical trial data but also their empirical experience with individual patients to inform their thinking on therapeutic options. For payers, coverage decisions on dermatology treatments are increasingly driven by real-world evidence.

Integrating sponsor and patient priorities

Sponsors may be under the impression that there is an inherent tension between their clinical trial-related priorities and the priorities of patients. However, this is usually not the case.

For sponsors, the top priority is the generation of reliable, high-quality data to support regulatory approval. This data relies on identifying, recruiting, and retaining the right population of patients and promoting adherence to the clinical trial protocol.

Patients considering enrollment in a dermatology clinical trial are typically seeking a correct diagnosis, the opportunity to access a new treatment option, and improve their skin condition and quality of life. Patients may also be driven by the desire to contribute to the body of knowledge and provide benefit to others with the same condition in the future. Whatever their motivation, patients are more likely to remain in a study if participation does not significantly inconvenience their daily life.

By engaging in dialogue with prospective study participants and understanding what is important to them, sponsors can successfully integrate patient priorities into their study designs in even the most challenging rare and pediatric indications. This is also an opportunity for sponsors to differentiate their trials, especially in indications where there may be hundreds of trials competing for the same patient pool.

Patient feedback can be invaluable for optimizing study design, recruitment and enrollment, and study implementation.

 Recruiting, enrolling, and retaining the right population of patients begins with creating a patient-focused protocol. Inviting patients and their caregivers to review a draft protocol gives sponsors the chance to solicit honest feedback on whether the trial burden is acceptable and whether the proposed assessments and endpoints make sense. Patients may even point out missed opportunities or potential barriers to success that the sponsor has overlooked.

In rare dermatology conditions, where the natural history of the disease is poorly understood, and defined endpoints are lacking, patient input can be invaluable in shaping trial objectives and then creating endpoints to match those objectives.



 Involving prospective participants in the process of raising trial awareness and developing all patient-facing study-related documents helps sponsors ensure that their messaging is on-target, clear, and easy to understand. Patient feedback is also critical for identifying gaps in disease education that can be addressed in indication-specific or study-related websites or social media.

 When a study is meaningful to patients and their families and manageable from a participation perspective, it is more likely to succeed. Ensuring that study participant and their caregivers understand and are on board with the commitment required is the first step. To keep patients engaged, sponsors and contract research organizations (CROs) should anticipate and proactively address any challenges associated with study participation, such as travel and lodging requirements.

Establishing alliances with patient organizations and patient advocacy groups, creating patient advisory boards, and incorporating focus groups and surveys allow for ongoing and transparent exchanges that can help facilitate these conversations. This may be especially useful in rare dermatology clinical trials where challenges with recruitment, adherence, and retention are amplified due to small, geographically dispersed populations.

An intense focus on patient safety is a powerful framework for decision-making when it comes to study design. The first set of questions sponsors should be asking is how to safely recruit, enroll, and follow-up with patients and how to ensure patients feel safe about clinical trial participation. Over the past year, in response to pandemic-related restrictions, changes in study conduct have been sweeping through the industry. Increasingly, study visits and monitoring procedures are being adapted to make it both safer and more convenient for patients to participate in clinical trials.

A patient-focused approach to protocol design can help enhance safety and study engagement while minimizing the participation burden. Key factors to consider when designing studies include:

 Is it possible to implement eConsent or remote paper consent?

 How long should on-site visits be? Can some visits be remote? Which visits are essential for preserving study objectives and data integrity?

 Which strategies can be implemented at the study and site level to improve recruitment and engagement? Can these strategies be executed virtually?

 Can certain procedures be performed off-site by a home nurse? What assessments can be completed via mobile health technology? Are there wearables or apps that can be used to further decrease the burden of participation? What procedures are necessary, and what may be skipped or at least included as an optional procedure or assessment?

 Can source document verification (SDV) be reduced or performed remotely? Would a combination of central and remote monitoring work for the study without sacrificing data quality?

By making the patient the focus of the protocol, sponsors may benefit from increased study visibility, shorter timelines, and more efficient utilization of site staff and resources.

Implementing a successful dermatology trial

Based on our extensive clinical trial experience, we have identified three aspects of study implementation that are the cornerstones of successful studies:

 Working with a CRO that has an established network of investigators and sites with experience in the indication of interest can help to reduce paperwork and streamline start-up. In addition, getting a head start on rate-limiting activities—such as document translation and licensing of patient-reported outcomes questionnaires—can help keep studies on track.

 Intra- and inter-rater consistency is critical for dermatology studies and downstream regulatory submissions. Developing and rolling out rigorous rater training, testing, and data monitoring can help ensure accuracy and consistency. Of course, requiring that the same investigator assesses the patient at every visit is ideal, but many sponsors will choose to keep the language in the protocol more forgiving to avoid frequent protocol deviations. That is why inter-rater variability may become a significant threat to data quality if not addressed proactively through the training.

 Minimizing SDV can help reduce duplication of work and time on site. Partnering with a CRO that has a risk-based quality management system that can analyze and review all data entered into the electronic case report form in real-time can reduce SDV while still ensuring data quality.

In a competitive clinical trial environment, sponsors are under pressure to optimize their clinical development strategy and planning to achieve regulatory approval as soon as possible. Partnering with a CRO that has experience in both dermatology and innovative clinical trial approaches can help sponsors differentiate their studies and facilitate recruitment. Using patient-focused study designs that prioritize safety and reduce participation burden without compromising data quality helps pave the path to market, answering the unmet needs of people with sub-optimally treated skin conditions.

, MD, MS, CCRP, is the Vice President, Medical Affairs, Dermatology and Medical Aesthetics, Premier Research

1Hay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP, Margolis DJ, Marks R et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol. 2014;134:1527–34

Karas L, et al. The impact of the Orphan Drug Act on Food and Drug Administration-approved therapies for rare skin diseases and skin-related cancers. J Am Acad Dermatol. 2019;81(3):867-877

U.S. Food and Drug Administration. FDA Patient-Focused Drug Development Guidance Series for Enhancing the Incorporation of the Patient’s Voice in Medical Product Development and Regulatory Decision Making. 

https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-series-enhancing-incorporation-patients-voice-medical

. Last updated June 18, 2020. Accessed March 12, 2021

European Medicines Agency. Patients and Consumers. 

https://www.ema.europa.eu/en/partners-networks/patients-consumers#framework-for-interaction-section

. Last updated December 22, 2014. Accessed April 5, 2021

European Medicines Agency. Reinforce patient relevance in evidence generation. 

https://www.ema.europa.eu/en/documents/presentation/presentation-ema-regulatory-science-2025-reinforce-patient-relevance-evidence-generation_en.pdf. Accessed April 5

Articles

How partnering with a CRO that has experience in both dermatology and innovative trial approaches can help sponsors differentiate their studies and facilitate recruitment. 

Navigating the New World of Dermatology Trials

While neither the lack of diversity in clinical research nor the need for patient centricity is new, recently, the clinical research community has been more determined than ever to ensure that we take steps now to increase both in the most impactful, effective way possible. But while many voices are in agreement that this drive is necessary—and, indeed, achievable—questions still remain, such as: How do we actually start creating those meaningful conversations?

In the summer of 2020, as the COVID-19 pandemic continued to spread, Leland Allen, MD, of St. Vincent’s Ascension, rapidly enrolled more than 200 diverse (including Black and Latino) patients in a coronavirus trial. What is important about this? He did this in Birmingham, Alabama…right in the vicinity of the infamous Tuskegee trials that are often implicated as the very catalyst that drove a destructive wedge between the Black community and researchers that has persisted for decades.

The secret? Trust. As a respected, connected member of the Birmingham community, Dr. Allen has invested time and effort in building a solid, authentic foundation of trust within the area. When he teamed with Elligo Health Research, a healthcare-enabling organization that connects patients with clinical research through their trusted care providers, patients had very little hesitation participating in a trial for COVID-19 research.

“There is nothing more important in the doctor and patient relationship than trust,” says Dr. Allen. “And that’s not just in the context of clinical trials. It’s in everything we do. If a patient or the patient’s family doesn’t trust the provider, or they don’t trust the information from the provider, they’re never going to ‘buy in’ to the treatment or medical advice.”

Building trust takes time, patience, and the willingness to be humble and open. But there are no shortcuts if researchers truly want to be part of the change that will ultimately increase diversity in clinical research in a way that is sustaining and authentic. Building trust includes:

Showing your worthiness of patients’ trust.

 The first step is taking an honest look in the mirror and examining your own behavior. “Obviously, if you have time to build a personal relationship with a patient, that’s best,” says Dr. Allen. “Then they recognize that you’re always honest and true to your word, and that trust grows. But sometimes you don’t have that opportunity. In that case, you need to convey to the patient that you are really interested in them as a person, and not just as someone with a disease or an illness.”

Even if there is bad news involved, Dr. Allen urges full transparency. “No one wants to hear bad news,” he says. “But everyone wants to hear the truth. If you’re trying to soften the blow and aren’t completely honest, that will backfire on you, because eventually the patient will figure it out. Then their thought process will be, if that doctor wasn’t honest with me, what else is he not going to be honest about? And especially when it comes to asking them to participate in research, they will have no desire to trust you or your peers.”


 Being willing to be vulnerable yourself increases the likelihood that you will better connect with patients in a manner that exudes trustworthiness. That means asking yourself, “Am I truly doing everything I can to be worthy of a patient’s trust?” To help achieve that, paired with honesty, be sure to stay in “continually learning” mode so you are making your decisions with absolute confidence and assurance.

“Especially in clinical research, our knowledge and understanding changes all the time,” says Dr. Allen. “The amount of information we have available to us increases exponentially. So, even if everyone is being honest and forthright in how we report data, and the way we conduct clinical trials, we need to be sure to have a healthy degree of suspicion to keep learning and studying and asking questions ourselves, to be sure we’re giving the right advice and doing the right thing with each and every patient.”


 Beyond individual efforts, building trust as an organization is paramount. Establishing an institutional reputation that endures and spreads in the community comes from creating a culture that carries enormous value. “Not only have I personally tried to establish relationships to build trust, but my hospital itself, St. Vincent’s Ascension, is the oldest hospital in the city,” Dr. Allen says. “We have a long track record in Birmingham. That’s why it’s important to do your best for every patient, because word gets around, and that hospital’s reputation can last for a very long time.”

Leading by example to establish that culture is the only way to make that happen, Dr. Allen says. And having that trustworthy reputation builds on itself. “Institutions tend to coalesce around a particular set of values,” he says. “If an institution focuses on trust and value above all, then it identifies and selects doctors and nurses and other staff who share their values. And that set of values acts as a screen to ensure that everyone in that organization is aligned. That’s part of the reason why I’m at St. Vincent’s. Because I believe in what they do and how they do it.”


 “Depending where you are in the United States, the climate may be different between researchers and diverse communities,” Dr. Allen says. “Here in Birmingham, we have to overcome deeply rooted racial divisions because of events that happened before many of us here were even alive.” But he believes that honest communication will help play a major role in rebuilding trust. “We need to acknowledge the past honestly, while still saying, ‘This is what we’re going to do—today—to protect you, and here is how you will benefit in being part of this study,’” he says. “And hopefully, because they trust you, they will have some faith and courage to step forward with you.”

In addition to direct communication, addressing language barriers plays a tremendous role, as well. Dr. Allen recently had a very sick patient who didn’t speak English. “His son didn’t speak English either,” he says. “Our discussion was through the patient’s niece, who was on the other end of a phone call, and while it was better than nothing, it was not optimal. So, I could walk in and smile, but that doesn’t convey nearly as much information as a direct conversation.” Including diverse researchers within your organization can help create a more solid bridge to trust to help minimize language barriers.

Building trust not only will help facilitate increased trial diversity, but in the process of working to establish that trust, it will organically create patient-centric relationships—and patient-centric trials—at the same time in a very authentic, collaborative way. Ultimately, this will pay off by paving the way to a more connected, healthier global community across a diverse range of populations.

 is the Medical Director, VP of Medical Affairs, at Elligo Health Research 

While many voices are in agreement that the drive for diversity is both necessary and achievable—the question still remains: How do we actually start creating those meaningful conversations?

Steps Toward Diversity in Clinical Trials: Building Authentic Trust

In a preview of the administration’s spending priorities for the coming fiscal year, the White House sent Congress a summary of “topline” funding requests this month, which continue efforts to combat the coronavirus pandemic and to restore the nation’s economic health. The main initiatives of the administration’s $1.5 trillion budget plan would increase outlays for education, climate change and housing, as well as public heath.

To better prepare for the next pandemic, the White House seeks a significant increase in discretionary funding for the Centers for Disease Control and Prevention (CDC), proposing a $1.6 billion increase to an $8.7 billion budget able to modernize data collection and boost support for local health departments. The National Strategic Stockpile would gain almost $1 billion to replenish critical supplies and continue restructuring efforts launched during the pandemic. There’s a mention here of the need to provide “investments to enhance FDA’s organizational capacity,” but more detail will be spelled out in the administration’s formal budget plan for 2022, which is expected next month. FDA may be further affected by initiatives designed to end the opioid crisis and the HIV/AIDS epidemic and the need to vet new treatments in these fields.

In hopes of gaining additional funding, FDA is clarifying how it would use further resources to “enhance” agency operations. In recent comments to the Alliance for a Stronger FDA, acting commissioner Janet Woodcock highlighted the need for funds to support further modernization of FDA data and information systems and to step up inspections and surveillance across drugs, biologics, vaccines and medical devices. These priority initiatives already will benefit from an added $500 million provided to FDA in recently enacted pandemic legislation, but “adequate funding” is needed to keep up with data modernization efforts, Woodcock noted. The pandemic made very clear, she said, that FDA and industry lack insight into the supply chain and need to invest more in this area. For modernizing data systems, FDA is working to establish an enterprise-wide platform with common data standards that will enable systems to talk to each other.

FDA furthermore could be involved in vetting research that arises from the administration’s most prominent initiative, the launch of the Advanced Research Projects Agency for Health (ARPA-H). The Biden plan provides $6.5 billion to establish this new entity within the National Institutes of Health (NIH) as a way to drive “transformational innovation” in health research and speed access to breakthrough treatments. ARPA-H initially would focus on cancer, diabetes and Alzheimer’s disease and is modeled after the military’s Defense Advanced Research Projects Agency (DARPA), with project funding decisions made by program managers, as opposed to the peer-review process of NIH research institutes. The aim is to be more flexible, with staff able to expand or cancel projects based on results.

While the biomedical research community generally applauded the ARPA-H plan, there is concern that the new initiative would reduce resources available to fund ongoing NIH programs and its main biomedical research mission. The new program would take up most of the $9 billion increase for NIH, which would see its budget rise to $51 billion. It’s not clear how this innovative research agency will be situated within NIH, who will oversee its operations, and how it will interact with biopharmaceutical companies and other agencies such as FDA. President Biden has been a strong advocate for cancer research and has discussed this kind of initiative previously with Congressional leaders. Some research advocates had hoped for a more independent entity that would stand alone within the Department of Health and Human Services (HHS) and will be looking to influence its mission and organization in the coming months of funding debate.

Separately, the White House announced the formation of a new national network to identify and track coronavirus mutations that raise fears of triggering another pandemic. President Biden unveiled a $1.7 billion plan to expand COVID genomic sequencing by CDC and state health departments and to create six “centers of excellence” at leading academic centers to share and analyze data on emerging disease threats.

 In addition to funding genomic sequencing capacity on the state and federal level, the new program would build a National Bioinformatics Infrastructure throughout the public health system. The White House aims to generate support for this and other public health programs by providing millions in funding to states to expand such efforts locally.

The administration’s full budget plan for fiscal year 2022 is slated to be released in May, later in the year than usual, but often the case with a change in administration. That will launch wide-ranging debate on ARPA-H, pandemic preparedness, and multiple new proposals.

https://www.whitehouse.gov/wp-content/uploads/2021/04/FY2022-Discretionary-Request.pdf

https://www.whitehouse.gov/briefing-room/statements-releases/2021/04/16/fact-sheet-biden-administration-announces-1-7-billion-investment-to-fight-covid-19-variants/

White House’s summary of “topline” funding requests this month continues efforts to combat coronavirus pandemic and to restore the nation’s economic health.

Biden Seeks Added Funding for Medical Research, Disease Tracking

Just in case anyone suspected FDA of over-reacting to problems at this troubled vaccine production site—or that any poor quality materials could be released—FDA officials have taken the unusual step of issuing the closeout report (form 483) on its just-completed re-inspection of Emergent BioSolutions’ Baltimore manufacturing facility. The report cites multiple ongoing violations that undermine assurance of quality in products from this plant and the need for a continuing “pause” in production.

FDA acting commissioner Janet Woodcock and Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), issued a forceful statement emphasizing the importance of thorough FDA inspections and review of quality procedures to ensure product quality.

 These FDA leaders aim to reassure the public that no vaccine will be released from the Emergent facility until FDA can assure it meets standards.

FDA inspectors found violations in last week’s inspection raise the risk of product cross-contamination and unsanitary conditions, specifically citing improper cleaning, lack of written procedures, faulty handling of raw materials and containers, and inadequate employee training to perform required job functions.

 And these are many of the same issues cited in by FDA inspectors in previous site visits, indicating that Emergent has failed to address multiple ongoing problems.

The situation now has drawn attention on Capitol Hill. Leaders of the House Oversight & Reform Committee and its Select Subcommittee on the Coronavirus Crisis have opened an investigation into how Emergent lobbying and political connections may have influenced continued funding for vaccine manufacturing, despite ongoing regulatory issues.

Woodcock and Marks emphasize that they are “doing everything we can” to ensure that COVID-19 vaccines for Americans meet FDA’s high standards for quality, safety and effectiveness. The result, they hope, is that FDA will maintain the public’s trust in its operations.

https://content.govdelivery.com/accounts/USFDA/bulletins/2ce64ec

https://www.fda.gov/media/147762/download?utm_medium=email&utm_source=govdelivery

https://coronavirus.house.gov/news/press-releases/maloney-and-clyburn-launch-investigation-emergent-biosolutions-profits-and

FDA officials have taken the unusual step of issuing the closeout report (form 483) on its just-completed re-inspection of Emergent BioSolutions’ Baltimore manufacturing facility.

FDA Unveils Extensive Manufacturing Violations at Emergent

Reify Health has announced that AstraZeneca has selected StudyTeam, a patient enrollment management platform, for clinical development across its breast cancer investigational therapy portfolio. Reify Health’s cloud-based solutions connect and empower the clinical trial ecosystem, starting with effective patient recruitment and enrollment. With its use of StudyTeam, AstraZeneca reinforces its reputation as a global sponsor of choice at breast cancer research sites.

AstraZeneca will expand use of the StudyTeam platform, including deployment of the Smart Patient Discovery feature. Information from a sponsor’s protocol can now be used to suggest potential patients to any research site coordinator using the StudyTeam system.

AstraZeneca Selects Reify Health’s StudyTeam for Breast Cancer Trial Pipeline

Syneos Health and Medable have announced a partnership to deliver decentralized capabilities to Syneos Health with the aim of increasing clinical trial diversity, while also aiming to improving patient access and experiences.

Syneos Health will gain access to Medable’s digital platform as well as deliver a decentralized digital solution to Syneos Health customers tailored to the specific attributes and requirements for conducting non-interventional research.

Medable will also now be part of the Syneos Health Dynamic Assembly network, an open ecosystem of data and technology collaborators committed to delivering solutions designed to strategically address the nuances of each customer engagement.

Syneos Health Partners with Medable to Expand Decentralized Solutions

Just two weeks after instructing Johnson & Johnson to take over operations at Emergent BioSolution’s noncompliant Baltimore manufacturing operation, FDA has called a halt in production of vaccine drug substance and to quarantine all remaining product at the Bayview plant. FDA initiated a “for cause” inspection of the facility last week to follow-up on violations found in an inspection last year, but requested the shut-down on April 16, 2021, according to an 8-K disclosure form filed by Emergent.

This latest enforcement action further muddies the supply outlook for J&J’s troubled COVID-19 vaccine, which separately is being reviewed by FDA and the Centers for Disease Control and Prevention (CDC) as to the cause of rare blood clots following vaccination. The feds had stopped distribution and use of the J&J vaccine pending further review of the safety issues. Meanwhile, Emergent evidently has produced more than 60 million doses of the J&J vaccine, but cannot release the drug substance to a finish-and-fill operation until FDA certifies the Baltimore plant as meeting good manufacturing practices.

FDA had cited serious quality concerns at Emergent’s Bayview plant in an inspection in April 2020, as previously reported 

 That situation was disclosed when Emergent reported last month that it had to discard 15 million doses of the J&J vaccine drug substance due to possible cross-contamination of two vaccines. Journalists and investigators have further uncovered additional government reports and complaints about Emergent’s operations and practices, raising ongoing questions about how and why federal health officials continued to expand and extend contracts with the company.

The FDA form 483 inspection report issued a year ago described inadequate controls for computer and records systems, disregard of established test procedures and laboratory control mechanisms, failure to investigate deviations from test methods, unclear quality control unit responsibilities and procedures, and lack of employee training on cGMP practices. A final observation cited deficient operations to prevent contamination or mix-ups of products by having separate or defined areas for holding rejected components before disposition. FDA and other government agencies were aware of the serious quality control issues at the Emergent facility, even before the discovery that millions of doses of J&J vaccine doses had to be discarded due to a mix-up with vaccine ingredient being produced for AstraZeneca.

Even though J&J assumed responsibility for manufacturing its vaccine drug substance at the Emergent facility two weeks ago, that apparently was not sufficient time to address the systemic manufacturing issues identified by FDA. At that time, Emergent executives noted that it was receiving an additional $23 million from the Biomedical Advanced Research and Development Authority (BARDA) to improve its manufacturing operations to expand J&J vaccine production and downplayed its quality control issues.

 Hopefully those and other government funds will be used to resolve the vaccine quality issues in time to be useful.

https://investors.emergentbiosolutions.com/static-files/eeb6d4b8-ff62-41a5-9cdc-ed7b1214d576

https://investors.emergentbiosolutions.com/news-releases/news-release-details/company-statement-emergent-biosolutions-statement-status-current

Just two weeks after instructing Johnson & Johnson to take over operations at Emergent BioSolution’s noncompliant Baltimore manufacturing operation, FDA has called a halt in production of vaccine drug substance and to quarantine all remaining product at the Bayview plant.

FDA Shuts Down Emergent Vaccine Facility

Clinerion has extended its patient coverage in Brazil to four new hospitals with the help of partner iHealth Group. This raises the footprint of Clinerion’s Patient Network Explorer to 17 healthcare organizations and over 7 million patients.

The four newest Brazilian hospitals to join the global community of partner hospitals on Clinerion’s Patient Network Explorer platform are:

Hospital São Lucas—PUCRS, Porto Alegre, Rio Grande do Sul

Hospital Martagão Gesteira, Salvador, Bahia

Centro Regional Integrado de Oncologia (CRIO), Fortaleza, Ceará

They are projected to go online in Patient Network Explorer by the end of May 2021. The hospital network in Brazil comprises hospitals of varied sizes, locations and specializations. 

Clinerion’s Patient Network Explorer Adds Four New Hospitals in Brazil

Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.

The European Parliament's health committee is hammering home some of the lessons from the COVID pandemic, which demonstrated so clearly that Europe, both at EU level and among its 27 member countries, "was not ready to deal with public health emergencies." In an April 15 debate, MEPs restated—yet again—the need for changes to the way the EU operates in terms of health policy. Not the first such demand, but the latest in what is becoming a tidal wave of calls for a firmer grip on policies affecting the well-being of its 450 million citizens.

"Despite having experienced previous threats, health structures were not geared towards this possibility," said Spanish socialist Nicolas González Casares, who is leading the parliament's examination of EU plans for upgrading the role of the European Medicines Agency in the wake of the devastation wrought by the pandemic. He attributed the inadequacy to budget cuts that have "diminished the adaptive capacities of our health systems," and pointed to the desperate attempts to cope over the last year as the European Commission and EMA "have had to act by setting up ad hoc structures to achieve a better and more coordinated response."

He told his fellow MEPs that "there is a need for the Union to equip itself with an appropriate institutional framework to deal with emergencies such as the one we are experiencing, without having to improvise, with a clear mandate, and by providing a legal framework for EU institutions to play a more active role." And first up is the proposal for a strengthened mandate of EMA. However, the principal objective of his plea is not to arrange for faster authorization of new medicines to tackle pandemics, not to offer incentives to innovate. Instead, this proposal is limited to bolting additional tasks onto EMA in relation to the specific issue of drug supplies. His draft recommendation is designed to avert the sort of penury in medicines that have hit health services since the crisis began, and he urges developing an institutional framework that defines who does what at any given moment, provides for monitoring and controlling the medicines supply chain, and an agreed definition of drug shortages. He wants to see steering groups set up to overview the production and supply chain for medicines and medical devices. He spoke at length on the need to coordinate and share the knowledge among the member states, the EU institutions and the pharmaceutical industry, and on the merits of creating a European medicines supply database.

"Had a regulation of this nature been in force before the pandemic, some issues such as shortages or the approval of new treatments would probably have been dealt with more deftly during the pandemic," remarked González Casares. He may be right. But readers of ACT will be relieved to be reassured that the EU response to COVID goes further than merely turning EMA into a pill-counting institution. As González Casares acknowledges in the document, he presented to the health committee, there are other EU initiatives underway of a more strategic nature. Another of these was debated and voted through by the committee on April 16: a new procedure to accelerate the EU-wide approval of vaccines adapted to COVID variants. This takes the form of a rapidly-created legal provision to ease the passage of vital new medicines through the EMA's authorization system. It will provide a simplified procedure for vaccines that have already received EU authorization but which are being adapted to be effective against variants of the virus.

Their vote—which now needs to be endorsed by the parliament as a whole at a future plenary session—comes after the release of an EMA reflection paper in February, and discussions in recent weeks with senior members of EMA, including Marco Cavaleri, head of its office on biological health threats and vaccine strategy. They received assurances on the criteria and operation of the new mechanism—including requirements that variant vaccines must be based on already approved/in use vaccines, and justification for the relevance of the variants included, based on disease surveillance and characterization of strains circulating at the time of selecting the variants. The efficacy of a monovalent or a multivalent variant vaccine against the variant strains may be inferred from provision of immunogenicity data after primary vaccination with the variant vaccine; and after a single dose of the variant vaccine when given to subjects who previously received primary vaccination with the parent vaccine. And as soon as a global forum is established to support SARS-CoV-2 strain selection for vaccines (such as has been discussed at the World Health Organization), the recommendations made should be consulted when selecting the variant strains.

This may prove a more effective measure to bring the pandemic under control—but it also underlines the growing conviction among many Europeans—and their politicians—that there is a need for more Europe in the field of health, and for progress towards a health union to match the EU's other major achievements such as its monetary union that created the Euro and its customs union that permits free trade across the internal borders between its member states.

Parliament's health committee is answering calls for a firmer grip on policies affecting the well-being of its 450 million citizens.

Dragging the EU into a More Health-Conscious Post-COVID Dynamic 

FDA is halting enforcement of a policy that limits prescribing and dispensing of Mifeprex (mifepristone), a widely used drug to induce a medical abortion in the very early stages of pregnancy. The revision allows doctors to authorize the pills via telemedicine and to make them available to patients through mail-order pharmacies while the pandemic continues, as a way to facilitate treatment while minimizing risky personal contact. And it puts FDA in the middle of the abortion debate.

Since approving Mifeprex for market in 2000, FDA has required women to obtain the drug directly from certified healthcare providers in certain clinics, medical offices and hospitals. The shared risk evaluation and mitigation strategy (REMS) program for the drug and generic equivalents calls for patients to be evaluated by trained medical professionals and blocked product dispending by retail or mail-order pharmacies or over the Internet. While medical professionals and women’s health advocates have opposed these restrictions for years, the limitations appeared more egregious when the Trump administration dropped similar distribution restrictions for a number of high-risk medicines to ease patient access to treatment during the pandemic—but did not extend such flexibility to mifepristone, despite its strong record for being safe and effective.

Now FDA is modifying the requirement for in-person consultation, stating that the agency will exercise “enforcement discretion” regarding dispensing limitations during the public health emergency and will be flexible in permitting Mifepristone dispensing through the mail.

 FDA acting commissioner Janet Woodcock confirmed the change in letters to the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine.

FDA’s move was praised by ACOG leaders, who sought and gained federal court approval in July 2020 for FDA to suspend its restriction on mifepristone dispensing directly to the patient in a clinic or medical office.

 The judge cancelled the prescribing restrictions on the basis that requiring women to travel to clinics in person to obtain the pill put them at risk of COVID infection. However, the Trump administration appealed the ruling, and the Supreme Court overrode that decision in January 2021, restoring the requirement that individuals seeking medication abortions to obtain the pills in person.

Now FDA has moderated the in-person prescribing requirement, supported by evidence from continued review of adverse events related to Mifeprex during the six months last year when the more liberal dispensing policy was in effect. Woodcock explained in her letter that FDA reviewed studies related to mifepristone safety and adverse event reports from January 2020 to January 2021 and found no evidence that remote patient consults raised serious safety issues, such as sepsis infection, bleeding or ectopic pregnancy.

The debate reflects how Mifeprex has become more widely used to halt unwanted pregnanciesas state and federal policies have made surgical abortions more difficult to obtain. Abortion opponents seeking to limit access to mifepristone claim that a telemedicine appointment to discuss such treatment raises grave safety risks to patients. Several states are considering bills to ban the pills or make them even harder to obtain. However, state restrictions could become moot with more flexible video consultation policies that enable patients to obtain a prescription from a physician in another state and to receive the drug through the mail. Some women may be reluctant to take a pill that is banned in their home state for fear of arrest and charges, even though most doctors consider mifepristone safer than many common over-the-counter pain medications.

FDA announced its more flexible approach to Mifeprex prescribing as a deadline neared for a federal appeals court to decide a challenge to the Trump requirements upheld by the Supreme Court. A long list of leading medical societies, including the American Medical Association, the American Academy of Family Physicians and ACOG, sent a letter March 1 to President Biden and Vice President Harris urging “swift action” to end the prior administration’s “unscientific and discriminatory policy” that forces patients prescribed mifepristone for pregnancy termination to pick up their medications at a health center. They point out that such requirements contradict actions by FDA and other federal agencies to promote the use of telemedicine during the pandemic to ensure access to health care while limiting unnecessary contact.

Separately, the Biden administration has moved to repeal regulations instituted by the Trump administration that bar family planning clinics that receive federal funds from offering abortion referrals and counseling. That move was widely hailed by women’s health advocates, but strongly opposed by anti-abortion forces.

https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/questions-and-answers-mifeprex

https://www.acog.org/news/news-releases/2021/04/acog-applauds-fda-action-on-mifepristone-access-during-covid-19-pandemic

FDA is halting enforcement of a policy that limits prescribing and dispensing of Mifeprex (mifepristone), a widely used drug to induce a medical abortion in the very early stages of pregnancy.

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