FDA Authorizes Gilead's Remdesivir for COVID-19

When I was tasked with writing the CSR shells for MERCK's Hepatitis C drug ZEPATIER® in the battle to go head to head with  Gilead Sciences' (NASDAQ:GILD  Harvoni I mused about putting a dart board at my desk with  the GILD ticker symbol in the center. Again with Seqirus/CSL Behring I find myself competing with GILD as we race to help provide health care practitioners (HCPs) with drug therapies.

That's all to say happy to see any pharma company making strides and was pleased the FDA  granted an Emergency Use Authorization (EUA) to )for Gilead Sciences' remdesivir. Remdesivir hasn't been formally approved to treat any disease, but the US government's action via the FDA authorizes HCPs to use it on a temporary basis  to treat hospitalized patients with severe COVID-19. Read the full article at the Motley Fool.

Online Virology Course for Lay People Brought to you by TEL AVIV UNIVERSITY

Viruses & How to Beat Them: Cells, Immunity, Vaccines

IsraelX - Virus101x

There are 160+ COVID-19 vaccines and drugs in development ....

Before you wade into the dizzying numbers of therapies start here to review a primer on immunity. What's below is taken from the UK patient.portal website. There is active and passive immunity:

Active immunity - offer protection by injecting VIRUS  (live or inactive) right into the individual
This is the stimulation of the immune mechanism to produce antibodies by giving an antigen as a vaccine. Such vaccines may be:

• Live attenuated viruses (rubella, measles, oral polio, mumps) or bacteria - bacillus Calmette-Guérin (BCG).
• Inactivated viruses (parenteral polio, hepatitis A) or parts of the bacterium or virus (pneumococcal vaccine, influenza).
• Inactivated bacterial toxins (diphtheria and tetanus).
• Genetically engineered (hepatitis B vaccine).

Passive Immunity - backdoor method -- offer protection via injecting immunoblogins or antibodies into the individual.  Immunoglobulins are glycoprotein molecules produced by plasma cells (white blood cells). They act as a critical part of the immune response by specifically recognizing and binding to particular antigens, such as bacteria or viruses, and aiding in their destruction.

This is achieved by giving immunoglobulins and the protection is immediate but lasts only a few weeks.

There are two types of immunoglobulins:

• Human normal immunoglobulin (HNIG) from pooled plasma. This contains antibodies to infections prevalent in the donor population. Some of these, such as that for hepatitis A, may be falling, ultimately affording less protection.
• Specific immunoglobulin for tetanus, varicella-zoster virus, rabies and hepatitis B. These are derived from pooled serum of convalescent patients.

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CSL Executive VEEP: Leaders lead during uncertainty - there is no question that we are all experiencing the impact of COVID-19

CSL Behring and Takeda Pharmaceutical Company Limited are leading a joint effort with Biotest, BPL Group, LFB, and Octapharm to develop a potential plasma-derived therapy for treating COVID-19. The alliance started immediately with the investigational development of one, unbranded anti-SARS-CoV-2 polyclonal hyperimmune immunoglobulin medicine with the potential to treat individuals with serious complications from COVID-19.


“Leaders lead during uncertainty. There is no question that we are all experiencing the impact of COVID-19,” said Bill Mezzanotte, CSL Behring’s Executive Vice President and Head of Research and Development.Read more from B. Mezzanote.

FDA Approves Pandemic Flu Vaccine From SEQIRUS/CSL Behring

Medscape  reports that the FDA has approved Audenz, “the first and only adjuvanted, cell-based pandemic vaccine to provide active immunization against the influenza A virus H5N1 strain.” According to Medscape, “Influenza A (H5N1) monovalent vaccine, adjuvanted...is for use in individuals aged 6 months and older.” The vaccine is “designed to be rapidly deployed to help protect the US population and can be stockpiled for first responders in the event of a pandemic.”

  

Healio also covers the story.

Leading pharmaceutical companies and total global vaccine market share 2017 and 2024

The top ten pharmaceutical companies based on global vaccine revenue market share in 2017 and a projection for 2024 include companies like CSL Behring.

In 2017, GlaxoSmithKline (GSK) was the top pharmaceutical company and held about 24 percent of the global vaccine market by revenue. GSK is expected to maintain their position as the top company and even gain a small amount of the market until 2024. Pfizer is expected to account for some 16 percent of the global vaccine market by 2024, largely due to success with its pneumococcal vaccine, Prevnar 13. A vaccine often contains an agent that is made from a weakened form of a disease microbe, that is then used to stimulate the body's immune system to destroy and recognize the microorganism in case of later exposures.

Seqirus/CSL Behring is among the global leaders and has provided patient consumers new vaccines with these recent approvals: AUDENZ  the first and only adjuvanted, cell-based pandemic vaccine to provide active immunization against the influenza A virus H5N1 strain; FLUAD a seasonal vaccine in February 2020 in the US; and FLUCELVAX a seasonal vaccine for children and adults in Canada.

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Global biotech leader CSL has formally offered to help governments around the world

(March 2020) -- To speed treatments, global biotech leader CSL is lend ingthe company’s expertise in science and manufacturing to address the recent coronavirus global pandemic.  The company is exploring development of a hyperimmune serum that could be derived from the blood plasma of people who have recovered from coronavirus. Once an adequate number of recovered patients is identified, it’s our hope that CSL could begin to collect their plasma and create a hyperimmune serum enriched with COV-19 antibodies to use as a therapy.

Though more research and testing is necessary, it’s believed that antibodies found in the plasma of now-healthy COVID-19 patients could potentially be used to boost the immune response of those who are struggling with the infection. By now it is well known that coronavirus causes mild flu-like symptoms in many, but others who are older than 60 or have additional medical conditions are at high risk of fatal complications.

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Clinical Trial Disclosure and Transparency:  Find this  article on Pfizer.com.

Compliance with the requirement to report results on the EU Clinical Trials Register: cohort study and web resource
https://youtu.be/7LkCEFc7XbYsas

Twenty odd years ago if a patient or wanted to learn about new trials a it was an interesting journey. Individual academic institutions and pharmaceutical organizations around the world kept records and often eagerly registered trials to promote enrollment, the sharing of results was at times haphazard and international and national repositories aggregating thousands of trials per disease indication was slow in coming.

By 1997 the NIH in America, as well the Europeans 4 years on in 2001, and international bodies such as the World Health Organization (WHO) began offering industry and academia guidelines and structure: what to report and when, specifying exact guidelines on how many months after a trial's completion to publish results. Medical writers have been an important voice with the International Committee of Medical Journal Editors (ICMJE)  in 2/2019 specifying data sharing disclosure requirements for candidate articles. For more information, an older presentation on disclosure (circa 2005) from Deborah Zarin, MD of ClinicalTrials.gov is here.

The Challenges of Writing Patient / Safety Narratives - by the Quanticate Medical Writing Team

There are a number of unique challenges that a medical writer might encounter while writing / managing patient / safety narrative projects. This blog describes the scope of narrative projects and outlines the associated challenges and provides some ideas to help you successfully manage narrative projects.

What is the purpose of Patient Narratives?

Patient narratives are written for deaths, serious adverse events (SAEs), or adverse events (AEs) of special clinical interest (eg, AEs associated with the mechanism of action being studied, laboratory results of special interest, regulatory requirements etc.) and those leading to permanent discontinuation from a clinical trial. Patient narratives form an important component of clinical study reports (CSRs) and pharmacovigilance services  (e.g. post marketing safety reports). As per International Conference on Harmonisation (ICH) E3 (Section 12.3.2), a patient narrative should describe:

• The nature, intensity and outcome of the event
• Clinical course leading to the event
• Timing of study drug administration
• Relevant laboratory measures
• Counter measures
• Action taken with the study drug in relation to the event
• Post mortem findings (if applicable)
• Investigator’s and sponsor’s opinion on causality

Additionally, patient identifier, age, gender, clinical condition, disease being treated, relevant medical history, concomitant and prior medications should be included.

All this information is extracted from the source files (e.g. Council for International Organisations of Medical Sciences [CIOMS] form, Case Report Form [CRF], MedWatch form, Data Clarification Form [DCF], summary tables, and listings). Sometimes, the CIOMS form can be directly attached as an appendix to the CSR.

Challenges of Narrative Writing

An early challenge, for sponsors, is to identify the approximate number of narratives to be produced, which further determines the narrative format and timing of production (pre- or post database lock). If narratives are written before the data are final, updates are required based on the final clean data. This approach can be time consuming, but is more feasible for projects where a large number of narratives have to be produced and finalised quickly e.g. for a regulatory submission. Medical writers can provide effective guidance to clinical study teams during this process.

The majority of Phase II and Phase IV studies have a large number of patients meeting the narrative criteria as outlined in the narrative plan. Excellent project management skills are essential for tracking such projects where huge volumes of narratives have to be written, often by a team of medical writers. The importance of careful management should not be under estimated; ensuring accuracy and consistency across a large number of narratives is a time consuming and tricky task!

In a Clinical Research Organisation (CRO), completing a narrative project within a pre specified budget and time, whilst maintaining quality can be extremely critical for the writers and the business as a whole. As soon as possible, team agreement on the style and content should be sought; this will reduce the possibility of valuable time being lost due to changes requested by the study team during the project lifecycle.

Narrative writing involves expressing the messages clearly and effectively, whilst collating the relevant information from various sources, and liaising with medical experts. A narrative tells the complete story chronologically and holds together medically. Identifying and relating the ‘relevant’ medical history or laboratory result to the event of interest can be challenging.

Ideas to help you successfully manage narrative projects

Firstly, get upfront team agreement on the style and content. This sounds obvious, but in our experience most narrative projects fall down due to a simple lack of communication at the start. Clear and detailed instructions agreed upfront by the key members of the study team will avoid valuable time being lost later due to changes in scope and will save headaches in trying to maintain consistency across the documents.

The easiest way to do this is to produce an initial batch of 5-10 example narratives for client review as early as possible in the process. Example narratives can be written for those cases where the final data are available (e.g. resolved serious adverse events [SAEs] or discontinued subjects). The in house team can be trained on the client requirements after initial review comments have been received.

Some aspects that you should clarify include:

• Sentence structures (e.g. some clients prefer to start a sentence with a date)
• Date formats
• Which medical history and concomitant medications are considered relevant
• Inclusion or exclusion of normal ranges for laboratory results
• Trade or generic names for drugs

A comprehensive template that is flexible enough to suit client requirements whilst maintaining internal consistency can also prove to be a very effective tool.

A lot of re-work can be avoided by working and delivering narratives in batches. Periodic delivery in small batches of 5-10 narratives can provide ample time for team review and is considered a pragmatic approach. While sending the narratives for review, it is also advisable to clearly state the timeframe within which all review comments must be returned to avoid unnecessary delays.

Tracking is critical in projects where a large number of narratives have to be written for regulatory submissions. Microsoft Office Excel can be an excellent tracking tool for managing huge volumes of narratives. Important details in the spreadsheet could include key milestone dates, protocol and subject identification numbers, and events of interest.

A narrative project becomes more complex and difficult to manage when multiple writers are involved. In a multi-writer project, regular team meetings can help keep everyone on the same page, particularly if changes are requested based on client review. Ensuring that new narratives are written according to the new specifications AND ensuring that previously drafted narratives are updated, can be a challenging task! A useful clinical project management tip is to keep and regularly update a project specific ‘styleguide’ with notification posts sent out to the study team whenever an update is made. All writers working on the narrative project should have access to the latest version of the styleguide.

Quality Control (QC) is an important step in the delivery of a narrative project. One of the most common dilemmas faced by writers is to decide on the stage at which narrative QC should be performed. If time is not a constraint, QC must be performed at both interim (review) and final delivery stages. However, if there are pressing issues (e.g. imminent regulatory filing, timing of production with regards to database lock [e.g. pre database lock], a thorough and independent final QC should suffice.

The Art of Science Journalism

Science journalism is notoriously difficult. Not only must writers grapple with complicated topics, but they must also communicate them in a concise (preferably entertaining) manner for a general audience. That's a tall order. But rising to meet this challenge are the science bloggers, many of whom are scientists themselves. These writers, perhaps more so than traditional journalists, have helped impart science's joys, wonders, and lessons. At RealClearScience our primary mission is to aggregate the best science writing the Internet has to offer. Since our launch in October 2010, we have read literally thousands of articles from hundreds of writers. But there are a handful of bloggers who stand out from the rest. This elite handful of informative, unique bloggers gathered together on RealClearScience.com is in their opinion, 

For more read the article.

The Open Principle of Contributing to Wikipedia

Reprinted from MyScienceWorks.com


There are a number of common points and some potentially instructive differences between the open principles of Wikipedia contribution and those ruling research. Both sides were presented by Adrienne Alix, until recently director of programs for Wikimedia France, at the launch of WikiCristallo. This French project, co-organized by the association Amcsti, aims to bring more of one particular area of science—crystallography— to the largest encyclopedia ever known, as well as a Wiki sense of collaboration to the diffusion of science.

 

Seeking Credibility

Fundamental to both activities is, of course, citing one’s sources. In a Wikipedia article, though, which could be written by tens, hundreds or even thousands of people, the reader doesn’t care who authored which bit; he or she is looking for credible information. Wiki depends even more heavily on the sources cited than does a scientific article, since, in research, some of that sought-after credibility is carried by the identity of the author. The role of the expert is, in fact, profoundly different between the two worlds. In the realm of Wikipedia contribution, authors are judged on their actions, not at all on the titles they may hold. “Who you are isn’t really important,” Adrienne Alix explains. “That can be troubling for people.”

 

Open and Collaborative Process, Better Product

Troubling, maybe, but mightn’t it be a good idea for science to bow a little less to prestige? We’ve already seen the research an untitled, 15-year-old can do when given the chance. So, what else can science and scientists borrow from the realm of a community-born and -managed wealth of information? Above all, the efficacy of a collaborative exchange of knowledge.

Before Wikipedia was born in 2001, there was Nupedia. Experts submitted articles to this encyclopedia, also founded by Jimmy Wales, which were read and validated by their peers, but the whole process moved slowly. With the arrival of wiki software, several people could contribute easily to the same page, without any particular technical skills. It started taking off, spreading knowledge beyond the English-speaking world as users created pages in their own language. Wikipedia emerged not so much in the spirit of openness, initially, but because the system worked so much better than the traditional method of expert validation, Adrienne Alix says. The bet was that if the process were opened to all, the quality would improve—a wager that Wikipedia’s founders took to the open knowledge bank.

The Wikimedia family has proven the value of other open knowledge models, some of which can be adapted for and adopted by the research community. Indeed, Wikimedia Commons is a centralized repository of over 20,000,000 illustrations and multimedia files under open license that already takes a scientific approach to its cataloguing. In 2010 the Muséum de Toulouse, a French natural history museum, launched the Phoebus program, calling on volunteers to photograph and upload images of its collections. With full descriptions, in English and in French, the result is, essentially, an open, digital database of the museum’s collection. Wikimedia reports (in French) that, “every month, on average, over 3 million pages containing images from the project are visited on more than 260 linguistic versions of Wikipedia.” Talk about visibility. 

Wikipedia’s bookish cousin, Wikisource, is a library of public domain and Creative Commons works – the parallel of an open access archive of scientific publications. Here, the community collaborates to correct errors generated by the text recognition software used to scan the works. Adrienne Alix explained that the francophone Wikisource is used a great deal by schools in Africa, for example, where classes usually have to rely on photocopies of photocopies of books. “It’s pretty fantastic for them. All of the French literature is available, they can just print it out.” That testimonial has a familiar ring to it, to anyone aware of the arguments for opening up access to scientific results.

 

Share Where Your Audience Is and Take the Best of Both

Given the similarities between the goals of researchers and contributors to collaborative projects, it could make sense for anyone communicating science to take a step closer to Wikipedia. Part of the motivation, in the spirit of popularization, Adrienne Alix says, would quite simply be to share knowledge where the audience is: Wikipedia is the number one site for science and culture in the world, and we’ve all noticed that Wiki sites always appear among the first search results. Another goal of Wikimedia groups is to build bridges with science institutions, by way of projects like WikiCristallo working to enrich French-language crystallography content and introduce new Wikipedians to the tools and the stakes of sharing science, or via contribution workshops for researchers. Adrienne Alix sees it as “a public service approach, adapted to current practices. We have a choice: leave a barrier between institutional communications and projects like Wikimedia’s, or try to take the best of both.”