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GSK and Medicago announce collaboration to develop COVID-19 vaccine

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GSK and Medicago announce collaboration to develop COVID-19 vaccine
July 07, 2020: “GSK and Medicago announced a collaboration to develop and evaluate a COVID-19 candidate vaccine combining Medicago’s recombinant Coronavirus Virus-Like Particles (CoVLP) with GSK’s pandemic adjuvant system.

CoVLPs mimic the structure of the virus responsible for COVID-19 disease, allowing them to be recognised by the immune system.

Use of an adjuvant can be of particular importance in a pandemic situation as it may boost the immune response and reduce the amount of antigen required per dose, allowing more vaccine doses to be produced and therefore contributing to protecting more people.

Pre-clinical results with Medicago’s CoVLP vaccine candidate demonstrated a high level of neutralizing antibodies following a single dose when administered with an adjuvant.

Phase 1 clinical testing is planned to start in mid-July and will evaluate the safety and immunogenicity of three different dose levels of antigen combined with GSKs pandemic adjuvant and in parallel with an adjuvant from another company, administered on a one- and two-dose vaccination schedule, given 21 days apart.

Subject to successful clinical development and regulatory considerations, the companies aim to complete development and make the vaccine available, in the first half of 2021.

Both companies will also evaluate expanding their collaboration to develop a post-pandemic vaccine COVID-19 candidate, should the need arise based on the further development of COVID-19 after the pandemic, and other infectious diseases.

The companies will use Medicago’s plant-based production platform to manufacture the COVID-19 vaccine antigen.

This innovative technology uses the leaves of a plant as bioreactors to produce the S-spike protein which self-assemble into VLPs for use in the CoVLP vaccine candidate.

It is highly scalable and can support the production of large amounts of the vaccine in a significantly shortened timeline.

Using this technology combined with GSKs proprietary adjuvant system, the companies expect to be able to manufacture approximately 100m doses by the end of 2021.

By the end of 2023, a large-scale facility under construction in Quebec City, Canada, is expected to deliver up to 1 billion doses annually.

The manufacturing platform has been used to produce a seasonal VLP flu vaccine and the license application is under review with the Canadian regulatory authority.

Dr Thomas Breuer, Chief Medical Officer, GSK Vaccines, said: “This agreement paves the way for an innovative vaccine option combining a scalable plant-based antigen technology with an adjuvant which has pandemic dose sparing capability. If successful, it will be a meaningful contributor in the fight against COVID-19.

Related News: Coronavirus treatment: Vaccines and drugs in the pipeline for COVID-19

Coronavirus treatment: List of Vaccines and drugs in the pipeline for COVID-19

We strongly believe that multiple vaccines are needed, including post-pandemic vaccines. This plant-based technology also shows promise beyond COVID-19 and has the potential to help prevent other infectious diseases.”

Dr Bruce Clark, President and CEO of Medicago, said: “We are about to begin clinical trials with our CoVLP vaccine candidate harnessing GSKs pandemic adjuvant technology against the virus that causes COVID-19.

This collaboration with GSK gives us access to a proven adjuvant which could enhance the effectiveness of our candidate vaccine, and also to a depth of scientific experience to support our development efforts.”

GSK and Medicago have entered into a binding agreement to develop and manufacture an adjuvanted COVID-19 vaccine.

Medicago is a privately held company jointly owned by Mitsubishi Tanabe Pharma (MTPC) and Philip Morris International (PMI), with a shareholding ratio of 67:33, respectively. “

PMI has signalled that it is willing to evaluate offers for its shareholding from parties that may be better suited to help Medicago on the next phase of its journey and has initiated a preliminary review to determine the optimal shareholding and governance structure for Medicago’s future success.”
https://www.gsk.com/en-gb/media/press-releases/gsk-and-medicago-announce-collaboration-to-develop-a-novel-adjuvanted-covid-19-candidate-vaccine/

Basics of case report form

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Basics of case report form

“Case report form (CRF) is designed to collect the patient data in a clinical trial as per the clinical trial protocol”

What is a case report form

In plain English, we can say that CRFs are the “forms” where patients related data is entered. These forms are built as per the requirement given in clinical trial protocol.

ICH defines it as “A printed, optical or electronic document designed to record all of the protocol – required information to be reported to the sponsor on each trial subject.”

Site personnel such as clinical research coordinator and principal investigator capture the subject’s data on the CRF, which is collected during their participation in a clinical trial/study.

CRF must be designed for optimal collection of data in accordance with the clinical trial protocol, regulatory requirements and shall enable the clinical research to answer the trial related questions.

A well-designed CRF represents the essential contents of the study protocol.

The case report form is designed once is protocol is finalised for the study and it can hold modified if a protocol is an amended.

Understand the various terms used

In this example, there are two forms Demography and Body temperature CRF, which are under one folder which is named as screening

The questions like date, result, gender is called variables and space where a site can enter the data are called “fields.

So now we have learnt below terminology regarding case report form.

Source: case report forms, FDA
  • Folder (screening)
  • Forms (or case report form)-Demography and Body measurement
  • Variables-All the questions like i.e Date, Date of birth etc
  • Fields-Places adjacent to variables where information/results are entered

You can find many examples of case report form on below link

https://www.accessdata.fda.gov/Static/widgets/tobacco/MRTP/09%20appendix-2h-smna-smkng-cstn/sm-08-01/1.%20CSR/16.1.2-sample-case-report-form.pdf

Type of case report form

There are two types of case report form-Paper and electronic case report forms

Paper CRF is the traditional method of data collection and a reasonable choice if studies are small or vary in design, while electronic CRFs are considered if studies are big with similar designs.

Nowadays, the electronic case report form is preferred over paper case report form

Advantages of electronic case report form (eCRF)

  • They are less time consuming
  • It allows sponsor/pharmaceutical companies to carry out large multicentric studies at the same time due to the ease of administration.
  • Data entry is easy and errors can be minimised
  • Duplication of CRF pages is avoided as repetitive data such as protocol ID, site code, subject ID will be generated by the system automatically from the first page to all others Case report forms.
  • In eCRF it is simple and fast to connect the data between two related CRF.
  • Rapid query resolution minimizes the time taken on obtaining site/investigator clarification and thus clean data is collected very easily, resulting in quicker locking of the database, faster regulatory submission and eventual approval.
  • Designing a paper CRF is a tedious job which may lead to data errors and misconclusions,
  • Chances of error during data transfer from the source document to paper CRF are quite common.

Disadvantages of eCase report form

an electronic case report form is designed on a tool that is called eDC tool.
Installation of the tool is complex and quite costly. maintenance of the software and high investment cost.

Regeneron announces the start of REGN-cov2 Phase 3 COVID-19 prevention trial with NIAID

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Regeneron announces the start of REGN-cov2 Phase 3 COVID-19 prevention trial with NIAID

July 6, 2020: “Regeneron Pharmaceuticals announced the initiation of late-stage clinical trials evaluating REGN-COV2, Regeneron’s investigational double-antibody cocktail for the treatment and prevention of COVID-19. 

A Phase 3 trial will evaluate REGN-COV2’s ability to prevent infection among uninfected people who have had close exposure to a COVID-19 patient (such as the patient’s housemate) and is being run jointly with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

REGN-COV2 has also moved into the Phase 2/3 portion of two adaptive Phase 1/2/3 trials testing the cocktail’s ability to treat hospitalized and non-hospitalized (or “ambulatory”) patients with COVID-19.

This clinical progress follows a positive review from the Independent Data Monitoring Committee of REGN-COV2 Phase 1 safety results in an initial cohort of 30 hospitalized and non-hospitalized patients with COVID-19.

The Phase 3 prevention trial is being conducted at approximately 100 sites and is expected to enroll 2,000 patients in the U.S.; the trial will assess SARS-CoV-2 infection status.

The two Phase 2/3 treatment trials in hospitalized (estimated enrollment =1,850) and non-hospitalized (estimated enrollment =1,050) patients are planned to be conducted at approximately 150 sites in the U.S., Brazil, Mexico and Chile, and will evaluate virologic and clinical endpoints, with preliminary data expected later this summer.

All trials are adaptively-designed, and the ultimate numbers of patients enrolled will depend on trial progress and insights from Phase 2 studies.

“We are running simultaneous adaptive trials in order to move as quickly as possible to provide a potential solution to prevent and treat COVID-19 infections, even in the midst of an ongoing global pandemic,” said George D. Yancopoulos, M.D., Ph.D., Co-Founder, President and Chief Scientific Officer of Regeneron.

“We are pleased to collaborate with NIAID to study REGN-COV2 in our quest to further prevent the spread of the virus with an anti-viral antibody cocktail that could be available much sooner than a vaccine.”

REGN-COV2
Regeneron scientists evaluated thousands of fully-human antibodies produced by the company’s proprietary VelocImmune® mice, which have been genetically-modified to have a human immune system, as well as antibodies isolated from humans who have recovered from COVID-19.

They selected the two most potent, non-competing and virus-neutralizing antibodies to create REGN-COV2 and have scaled up this dual-antibody cocktail for clinical use with the company’s in-house VelociMab® and manufacturing capabilities.

REGN-COV2’s two antibodies bind non-competitively to the critical receptor binding domain of the virus’s spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population, as detailed in recent Science publications. More recent research also demonstrates coverage against the now prevalent D614G variant.”

Regeneron used the same ‘rapid response’ capabilities and cocktail approach to developing REGN-EB3, a novel triple antibody treatment for Ebola that is now under regulatory review by the FDA. REGN-COV2’s development and manufacturing has been funded in part with federal funds from the BARDA under OT number: HHSO100201700020C.”

https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-start-regn-cov2-phase-3-covid-19-prevention

Novartis receives EC approval for Enerzair® Breezhaler® for uncontrolled asthma

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Novartis receives EC approval for Enerzair® Breezhaler® for uncontrolled asthma
July 7, 2020: “Novartis announced that the EC has approved Enerzair® Breezhaler® (QVM149; indacaterol acetate, glycopyrronium bromide and mometasone furoate [IND/GLY/MF]) as a maintenance treatment of asthma in adult patients not adequately controlled with a maintenance combination of a long‑acting beta2‑agonist (LABA) and a high-dose of an inhaled corticosteroid (ICS) who experienced one or more asthma exacerbations in the previous year.

Once-daily Enerzair Breezhaler is the first LABA/long-acting muscarinic antagonist (LAMA)/ICS fixed-dose combination available in the EU for these patients.

The approval also includes an optional digital companion with sensor and app that provides inhalation confirmation, medication reminders and access to objective data to better support therapeutic decisions.

The EC decision is applicable to all 27 European Union member states as well as the UK, Iceland, Norway and Liechtenstein.

Related News: Novartis receives CHMP positive opinion for Enerzair® Breezhaler® (QVM149), a potential first-in-class inhaled LABA/LAMA/ICS combination for uncontrolled asthma

“Novartis is working to reimagine medicine for people with uncontrolled asthma, who find it a challenge to achieve effective symptom and exacerbation control,” said Rod Wooten, Head of Global Marketing, Novartis Pharmaceuticals.

“The approval of Enerzair Breezhaler with sensor and app in the EU is an example of our commitment to utilizing data and digital offerings to make asthma control an achievable goal for patients and physicians.”

Enerzair Breezhaler is provided in a transparent capsule that allows patients to see that they have taken their medication and will be administered via the dose-confirming Breezhaler® device, which enables once-daily inhalation using a single inhaler.

The digital companion includes a sensor that attaches to the Breezhaler device and can be linked to the Propeller Health smartphone app, providing patients with inhalation confirmation, medication reminders and access to objective data that can be shared with their physician in order to help them make better therapeutic decisions.

“Today, over 45% of asthma patients at GINA Steps 4 and 5 remain uncontrolled, demonstrating the need for new treatments, delivery approaches and patient support to ensure that medication is taken correctly and treatment goals are reached,” said Professor David Price, Chair of Primary Care Respiratory Medicine, University of Aberdeen.

“Once-daily Enerzair Breezhaler plus a digital companion could help to facilitate greater collaborative disease management between physicians and patients in the EU whose asthma remains uncontrolled, despite LABA/ICS treatment.”

The EC approval is based on robust efficacy and safety data from over 3,000 asthma patients in the Phase III IRIDIUM study, in which once-daily Enerzair Breezhaler was superior to once-daily Atectura® Breezhaler® (QMF149; IND/MF) in improving the lung function of patients whose asthma is uncontrolled with LABA/ICS standard-of-care treatment.

In the IRIDIUM study, the key secondary endpoint was improvement in the Asthma Control Questionnaire score (ACQ-7) for Enerzair Breezhaler versus Atectura Breezhaler.

Both treatments delivered clinically meaningful improvements in this measure of symptoms from baseline at Week 26, but the key secondary endpoint was not met.

Among other secondary analyses, IRIDIUM explored asthma exacerbation rates, where statistically significant reductions were observed in moderate-to-severe and severe asthma exacerbation rates with Enerzair Breezhaler compared with an established LABA/ICS standard-of-care (twice-daily salmeterol xinafoate/fluticasone propionate [Sal/Flu]).

Safety findings were consistent with the known safety profiles of the monocomponents.

Once-daily Enerzair Breezhaler has been approved in Japan and Canada.

Once-daily Atectura Breezhaler has been approved in the EU as a maintenance treatment of asthma for adults and adolescents 12 years of age and older not adequately controlled with ICS and inhaled short-acting beta2-agonists (SABA) and in Canada and Japan.

Further regulatory reviews for Enerzair Breezhaler and Atectura Breezhaler are currently underway in multiple countries including Switzerland.

In keeping with the Novartis commitment to reduce the environmental impact of our asthma combinations, Enerzair Breezhaler and Atectura Breezhaler will both be available in the hydrofluoroalkane/chlorofluorocarbon (HFA/CFC)-free Breezhaler device.

Novartis aims to drive sustainability and has set ambitious targets to minimize its impact on climate, waste and water, including targets to become carbon neutral in company operations by 2025.

Uncontrolled Asthma
Asthma affects an estimated 358 million people worldwide and can cause a significant personal, health and financial burden when not adequately controlled.

Despite current therapy, over 40% of patients with asthma at Global Initiative for Asthma (GINA) Step 3, and over 45% at GINA Steps 4 and 5 remain uncontrolled.

Patients with uncontrolled asthma may downplay or underestimate the severity of their disease and are at a higher risk of exacerbation, hospitalization or death.

Barriers, such as less than optimal adherence, incorrect inhaler technique, treatment mismatch, safety issues with oral corticosteroids and ineligibility for biologics, have created an unmet medical need in asthma.

Enerzair Breezhaler (IND/GLY/MF) in the EU
The EC approved high-dose Enerzair Breezhaler (IND/GLY/MF) 150/50/160 μg once-daily as a maintenance treatment of asthma in adult patients not adequately controlled with a maintenance combination of a long‑acting beta2‑agonist (LABA) and a high-dose of an inhaled corticosteroid (ICS) who experienced one or more asthma exacerbations in the previous year.

This formulation combines the bronchodilation of indacaterol acetate (a LABA) and glycopyrronium bromide (a LAMA) with mometasone furoate (ICS) in a precise once-daily formulation, delivered via the dose-confirming Breezhaler device.

Glycopyrronium bromide certain use and formulation intellectual property were exclusively licensed to Novartis in April 2005 by Sosei Heptares and Vectura. Mometasone furoate is exclusively licensed to Novartis from a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA, for use in IND/GLY/MF (worldwide excluding the US).

Novartis developed the optional digital companion in collaboration with Propeller Health, which includes the Propeller Health app and sensor custom-built for the Breezhaler device.  

The sensor is a CE marked Medical Device, designed and licensed to Novartis for use with the Breezhaler inhaler worldwide.

The sensor includes a microchip, a microphone, Bluetooth capabilities, an antenna and a battery. The sensor does not alter the drug delivery characteristics of the Breezhaler inhaler itself but produces a recording of each administered dose.

Based on the patient’s recorded medication usage, personalized content is presented within the app to help the patient better self-manage their asthma.

IRIDIUM study
IRIDIUM was a Phase III, multicenter, randomized, double-blind, parallel-group study, designed to compare the efficacy and safety of Enerzair Breezhaler (IND/GLY/MF) with Atectura Breezhaler (IND/MF) in patients with asthma.

The purpose of the trial was to evaluate the efficacy and safety of two different doses of Enerzair Breezhaler (high: 150/50/160 μg and medium:150/50/80 μg), versus two corresponding Atectura Breezhaler doses (high: 150/320 μg and medium: 150/160 μg) in patients with uncontrolled asthma, as determined by pulmonary function testing and effects on asthma control.

All patients were required to be symptomatic at screening and to have one or more exacerbations in the previous year, despite being on treatment with medium or high stable doses of LABA/ICS.

Approximately 3,092 male and female adult patients with asthma were randomized 1:1:1:1:1 (approximately 618 patients in each of the treatment groups) to receive either:

  • Enerzair Breezhaler 150/50/80 μg (once-daily)
  • Enerzair Breezhaler 150/50/160 μg (once-daily)
  • Atectura Breezhaler 150/160 μg (once-daily)
  • Atectura Breezhaler 150/320 μg (once-daily)
  • Sal/Flu 50/500 μg (twice-daily)

The primary objective of this study was to demonstrate superiority of both high-dose Enerzair Breezhaler versus high-dose Atectura Breezhaler and medium-dose Enerzair Breezhaler versus medium-dose Atectura Breezhaler, all delivered once-daily, in improving trough FEV1 (volume of air that can be forced out in the first second of expiration approximately 24 hours post-administration of study drug) after 26 weeks of treatment in patients with asthma.

The key secondary objective was to demonstrate the superiority of both doses of Enerzair Breezhaler versus respective doses of Atectura Breezhaler, in improving Asthma Control Questionnaire (ACQ-7) score after 26 weeks of treatment in patients with asthma.

Other secondary analyses also included reduction of exacerbation rate, comparing high-dose Enerzair Breezhaler with high-dose Atectura Breezhaler and medium-dose Enerzair Breezhaler with medium-dose Atectura Breezhaler”.

Secondary analyses included efficacy comparisons for both doses of Enerzair Breezhaler compared with Sal/Flu (50/500 μg).”
https://www.novartis.com/news/media-releases/novartis-receives-ec-approval-enerzair-breezhaler-including-first-digital-companion-sensor-and-app-can-be-prescribed-alongside-treatment-uncontrolled-asthma-eu

Coronavirus (COVID-19) Update: Daily Roundup July 6, 2020

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Coronavirus (COVID-19) Update: Daily Roundup July 6, 2020

July 06, 2020: “The U.S. Food and Drug Administration announced the following actions taken in its ongoing response effort to the COVID-19 pandemic:

  • The FDA added content to the question-and-answer appendix in its guidance titled “Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency.”

    The updated guidance clarifies two previously suggested methods for obtaining informed consent from a hospitalized patient in isolation.

    In addition, the guidance includes a new question-and-answer regarding how to obtain informed consent from a prospective trial participant in certain circumstances where the enrollment timeframe is limited and the patient can receive a copy of an informed consent document electronically but cannot sign it electronically or print it out for signature.

    The guidance also clarifies recommendations on documenting details when using video conferencing for trial visits.
  • The FDA issued an emergency use authorization (EUA) for the third diagnostic test for detection and differentiation of the viruses that cause flu and COVID-19 in individuals suspected of COVID-19 by their healthcare provider to the Centers for Disease Control and Prevention (CDC).

    The FDA has previously issued EUAs to BioFire Diagnostics, LLC and QIAGEN GmbH for their tests, which include many other respiratory organisms in addition to the viruses that cause flu and COVID-19. These combination tests work by testing a single sample from a patient for multiple respiratory diseases.

    Tests based on taking just one sample from a patient may help alleviate the need for multiple sample collections, which means less discomfort for the patient with faster and more comprehensive results.

    The FDA encourages additional developers to work with the FDA on combination tests that may be useful in preserving critical testing resources during the upcoming flu season.
  • On July 2, 2020, the U.S. Food and Drug Administration (FDA) issued the second Emergency Use Authorization (EUA) for a COVID-19 antigen test.

    An antigen test is a diagnostic test that quickly detects fragments of proteins found on or within the virus by testing samples collected from the patient’s nasal cavity using swabs.

    The EUA was issued to Becton, Dickinson and Company (BD) for the BD Veritor System For Rapid Detection of SARS-CoV-2. Antigen tests can provide results in minutes, be produced at a lower cost than molecular tests, and potentially scale to test millions of Americans per day once multiple manufacturers enter the market.

    However, antigen tests may not detect all active infections, as they do not work the same way as a PCR test.

    The FDA will continue to support the development, review, and monitoring of tests to help ensure accuracy while balancing the urgent need for these critical diagnostics.
  • Testing updates:
    • To date, the FDA has currently authorized 164 tests under EUAs; these include 137 molecular tests, 25 antibody tests, and 2 antigen tests.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices.

The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-july-6-2020

What is Scientific Writing?

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What is Scientific Writing?

-By Aditi Jain

“INTRODUCTION

Scientific writing is a technical form of writing that is designed to communicate scientific information to an audience of peers, other scientists.

Depending on the specific  genre—a journal article, a scientific poster, or a research proposal, for example—some aspects of the writing may change, such as its purpose, audience.

The goal of scientific writing is to

  • communicate
  • Inform (new findings/information)
  • Interest and/or persuade the reader

Fundamental elements of good scientific writing

  • Clear
  • Precise
  • Logical (structure)

IMPORTANT HOLLMARK

1. Its primary audience is other scientists. Because of its intended audience, student-oriented or general-audience details, definitions, and explanations — which are often necessary in lab manuals or reports — are not terribly useful.

2. It is concise and precise. A goal of scientific writing is to communicate scientific information clearly and concisely.

3. It must be set within the context of other published work. Because science builds on and corrects itself over time, scientific writing must be situated in and reference the findings of previous work.

CHARACTERISTICS :

1. Clear
2.Simple
3. Impartial
4.Accurate
5. Objective
6.structural logical

IMPORTANCE OF SCIENTIFIC WRITING:

Writing is a very important part of science; it is used to document and communicate ideas, activities and findings to others. Scientific writing can take many forms from a lab notebook to a project report, or from a paper in an academic journal to an article in a scientific magazine.

SCIENTIFIC WRITING INCLUDE:

1.Peer reviewed journal articles that is primary research
2.Grant proposals
3.Literature review article

After completion of any research the scientific have to publish the result of the research it would written in scientific language and in a particular pattern that include:

1. Title ( statement of the research
2. Abstract ( short summary)
3. Introduction ( background and significance)
4. Material and method( Report of research)
5. Result (presentation of data)
6. Discussion section
7. Reference ( source of books)
8. Conclusion

All these point should be include in the report.

SCIENTIFIC WRITING CONVENTION:

This part of the guide covers the typical rules and conventions of scientific writing. They are important to follow because this is part of how scientists communicatewith each other. They are set out as follows:

1. A brief introduction to tables and figures
2. Defining terms and abbreviations
3. Are contractions okay?
4. What about exclamation marks or rhetorical questions?
5. Write to inform not impress
6. Should I be using the active or passive voice?
7. What tense should I use?”

UK study to research the long-term health impact of COVID-19

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UK study to research the long-term health impact of COVID-19
“The Health and Social Care Secretary has announced the launch of a major £8.4m research study into the long-term health effects of COVID-19 on hospitalised patients, which has been funded by the NIHR and UK Research and Innovation.

The researchers hope their findings will support the search for treatments for COVID-19 and the development of care pathways that will help patients recover as fully as possible after having experienced the disease.

Symptoms of COVID-19 have varied among those who have tested positive: some have displayed no symptoms, while others have developed severe pneumonia and, tragically, have even lost their lives.

For those who were hospitalised and have since been discharged, it is not yet clear what their medical, psychological and rehabilitation needs will be to enable them to make as full a recovery as possible.

The Post-Hospitalisation COVID-19 Study (PHOSP-COVID), led by the NIHR Leicester Biomedical Research Centre, will draw on expertise from a consortium of leading researchers and doctors from across the UK to assess the impact of COVID-19 on patient health and recovery.

This includes looking at possible ways to help improve the mental health of patients hospitalised with coronavirus, and how individual characteristics influence recovery, such as gender or ethnicity.

The study aims to recruit around 10,000 people from across all four nations of the UK who have been discharged from hospital after having COVID-19.

The researchers will follow up participants for up to 12 months or longer to collect and analyse routine clinical data, such as blood test results and lung volume measurements.

Enhanced clinical data, such as samples to look for the presence or absence of specific molecules (biomarkers), will also be collected for some patients, and this data may be linked to their other medical records.

The study data will be used to determine the short to long term health issues experienced by people who have been hospitalised with COVID-19 and relate these, where possible, to demographic data, clinical information and biomarkers.

The data will also help researchers understand which medicines and care pathways patients received in hospital and follow-up visits were most helpful, and to pinpoint their effectiveness in groups of particular patients.

The PHOSP-COVID team will then develop sub-trials of new strategies for clinical care, including personalised treatments for groups of patients based on the particular disease characteristics they show as a result of having COVID-19 – such as kidney damage, or lasting heart and circulatory problems.

Professor Chris Brightling, Professor of Respiratory Medicine at the University of Leicester and Consultant Respiratory Physician at Leicester’s Hospitals, is the chief investigator for the study.

He said: “As we emerge from the first wave of the pandemic, we have new insights into the acute phase of this disease but very little information about patients’ long- term needs.

“It is vitally important that we rapidly gather evidence on the longer term consequences of contracting severe COVID-19 so we can develop and test new treatment strategies for them and other people affected by future waves of the disease.”

Chief Medical Officer and NIHR co-lead Professor Chris Whitty said: “As well as the immediate health impacts of the virus, it is also important to look at the longer-term impacts on health, which may be significant.

“We have rightly focused on mortality, and what the UK can do straight away to protect lives, but we should also look at how COVID-19 impacts on the health of people after they have recovered from the immediate disease.

“This UKRI and NIHR funded study is one of the first steps in doing this.”

UK Research and Innovation Chief Executive, Professor Ottoline Leyser, said: “We have much to learn about the long-term health impacts of COVID-19 and its management in hospital, including the effects of debilitating lung and heart conditions, fatigue, trauma and the mental health and wellbeing of patients.

“UKRI is collaborating with NIHR to fund one of the world’s largest studies to track the long-term effects of the virus after hospital treatment, recognising that for many people survival may be just the start of a long road to recovery.

“This study will support the development of better care and rehabilitation and, we hope, improve the lives of survivors.”

This study is one of a number of COVID-19 studies that have been given urgent public health research status by the Department of Health and Social Care, to expedite its delivery in the health and care system.

PHOSP-COVID will establish a national platform that embeds research into a standardised clinical and biosampling pathway, integrating with ISARIC-4C and utilising the NIHR Bioresource.

The study is supported by NIHR’s Biomedical Research Centres and the NIHR Respiratory Translational Research Collaboration, in collaboration with the Scottish, Welsh and Northern Ireland COVID-19 networks, the NIHR Mental Health Translational Research Collaboration and the NIHR Clinical Research Network Respiratory Specialty.

Professor Melanie Davies, Director of the NIHR Leicester Biomedical Research Centre, said: “The purpose of a Biomedical Research Centre is to translate scientific breakthroughs into benefits for patients at pace.

“The coronavirus pandemic has highlighted the value of centres like ours in Leicester where we are leading research embedded into clinical care settings, which will have a direct impact on patient care, and we are delighted to be awarded this prestigious funding to continue our exemplary record in the fight against coronavirus.”

The data collected during the study will also be used globally, collaborating with consortia in Europe (European Respiratory Society) and Canada (Canadian Thoracic Society), to understand the long term impacts of COVID-19 on health worldwide.

Health and Social Care Secretary Matt Hancock said: “As we continue our fight against this global pandemic, we are learning more and more about the impact the disease can have not only on immediate health, but longer term physical and mental health too.

“This world-leading study is another fantastic contribution from the UK’s world-leading life sciences and research sector. It will also help to ensure future treatment can be tailored as much as possible to the person.”
https://pharmafield.co.uk/pharma_news/major-study-into-covid-19-long-term-health-effects/

Major study into COVID-19 long-term health effects

Surrogate Endpoint (Marker): Definition and Examples

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Surrogate Endpoint (Marker): Definition and Examples

“As per National Cancer Institute : In clinical trials, an indicator or sign used in place of another to tell if a treatment works. Surrogate endpoints include a shrinking tumor or lower biomarker levels.

They may be used instead of stronger indicators, such as longer survival or improved quality of life, because the results of the trial can be measured sooner.

The use of surrogate endpoints in clinical trials may allow earlier approval of new drugs to treat serious or life-threatening diseases, such as cancer. Surrogate endpoints are not always true indicators or signs of how well a treatment works.

In other words, a surrogate endpoint (or surrogate marker) in clinical trials is a measure of the efficacy of a particular treatment that may correspond with a true therapeutic outcome, but may not actually have a assured relation.

Surrogate endpoints may be used in its place of clinical outcomes in some clinical trials.

For example, surrogate endpoints are used where clinical results, such as strokes, may take a long time to research, or when the health advantage of changing the surrogate endpoint is well known, such as managing blood pressure.

These are also seen in situations where it would be unethical to perform a therapeutic conclusion test. Extensive data must gather, including results from epidemiological research and clinical experiments, until a alternative conclusion can be recognized in favour of a clinical result.

Clinical studies are typically used to show that the surrogate endpoint can be used to forecast, or compare with, clinical benefit in a context of use. Surrogate endpoints that have completed this comprehensive evaluation are considered approved surrogate endpoints, and the FDA recognizes these endpoints as evidence of gain.

Between 2010 and 2012, the FDA approved 45 percent of new drugs based on a surrogate endpoint. Often surrogate endpoints will help rapid acceptance with less proof help because they “possibly predict a therapeutic gain.”

Why are surrogate endpoints important for medical product development?

When a surrogate endpoint clearly predicts a beneficial effect through appropriate studies, its use normally allows for more efficient drug development programs.

For example, many clinical trials, using a range of different blood pressure lowering medications, have demonstrated that reducing systolic blood pressure reduced the risk of stroke.

Measurement of decrease in the surrogate endpoint of systolic blood pressure will also reflect the clinical outcome of the stroke, and clinical trials aimed at decreasing the risk of stroke can be carried out more rapidly in smaller populations using this validated surrogate endpoint.

Adult Surrogate Endpoint Table

Adult Surrogate Endpoint Table

Disease or UsePatient PopulationSurrogate EndpointType of approval appropriate forDrug mechanism of action
Acute Bronchospasm  Patients with acute bronchospasm associated with reversible obstructive airway disease or exerciseForced expiratory volume in 1 second (FEV1)TraditionalBeta-2 adrenergic agonist
Anthrax vaccinePersons at high risk of exposure to anthraxAnti-protective antigen antibody response             TraditionalInduction of immunity
Acute BronchospasmPatients with acute bronchospasm associated with reversible obstructive airway disease or exerciseForced expiratory volume in 1 second (FEV1)TraditionalBeta-2 adrenergic agonist
Benign hematologyPatients with Thrombocytopenia due to immune (idiopathic) thrombocytopenia or chronic hepatitis CPlatelet count responseTraditionalMechanism agnostic*
Benign hematology       Patients with sickle cell disease        Hemoglobin response rateAcceleratedHemoglobin S polymerization inhibitor
Cancer: hematological malignanciesPatients with Acute Lymphoblastic LeukemiaSerum asparaginaseTraditionalAsparagine-specific enzyme
Cancer: solid tumors Patients with breast cancer; neuroblastomaEvent-free survival (EFS)˟Accelerated/Traditional§Mechanism agnostic*
Cushing’s diseasePatients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative    Urine free cortisol TraditionalSomatostatin analog
Diphtheria vaccine (in combination vaccines)Persons to be immunized against diphtheriaAnti-diphtheria toxoid antibody             TraditionalInduction of immunity
Exocrine pancreatic insufficiencyPatients with exocrine pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, pancreatectomy, or other conditionsFecal coefficient of fat absorptionTraditionalCombination of porcine-derived lipases, proteases, and amylases
Fabry diseasePatients with Fabry diseaseHistological reduction of GL-3 inclusion burden in biopsied kidney interstitial capillaries (KIC)AcceleratedEnzyme replacement therapy, chaperone therapy
GoutPatients with goutSerum uric acidTraditionalXanthine oxidase inhibitor; URAT1 inhibitor
Hepatitis A (Hep A) vaccinePersons to be immunized against Hep AAnti-Hep A antigen antibody             TraditionalInduction of immunity
Hepatitis B (Hep B) vaccinePersons to be immunized against Hep BAnti-Hep B antigen antibodyTraditionalInduction of immunity
Hepatitis C Virus (HCV)Patients with HCV infection with or without cirrhosisSustained viral response (HCV-RNA)TraditionalAntiviral
Hepatitis D Virus (HDV)Patients with HDV infection with or without cirrhosis>2 log reduction in HDV-RNA plus normalization of ALT or HDV below the LLOQ˟AcceleratedAntiviral
Human Immunodeficiency Virus-1 (HIV-1)Patients with HIV-1Undetectable plasma HIV RNA              TraditionalAntiviral
Human PapillomavirusPersons (18 through 45 years of age) to be immunized against human papillomavirusCervical intraepithelial neoplasiaTraditionalInduction of immunity
Hyperkalemia    Patients with hyperkalemiaSerum potassiumTraditionalPotassium salts
Influenza vaccinePersons to be immunized against influenza Hemagglutination inhibition antibody               AcceleratedInduction of immunity
Japanese encephalitis vaccinePersons to be immunized against Japanese encephalitisNeutralizing antibodyTraditionalInduction of immunity
Lipodystrophy   Patients with congenital or acquired generalized lipodystrophySerum hemoglobin A1C, fasting glucose and triglyceridesTraditionalTraditionalLeptin analog
Male hypogonadotropic hypogonadism with inferilityMen with selected cases of hypogonadotropic hypogonadism with inferilitySperm parametersTraditionalGonadotropin

Pediatric Surrogate Endpoint Table

Disease or UsePatient PopulationSurrogate EndpointType of approval appropriate forDrug mechanism of action 
AcromegalyPatients with acromegaly who don’t respond to or cannot undergo other standard therapiesSerum growth hormone and serum insulin-like growth factor-I  (IGF-1)TraditionalSomatostatin analog 
Acute Bronchospasm              Patients with acute bronchospasm associated with reversible obstructive airway disease or exerciseForced expiratory volume in 1 second (FEV1)TraditionalBeta-2 adrenergic agonist 
Benign hematologyPatients with Thrombocytopenia due to immune (idiopathic) thrombocytopenia or chronic hepatitis CPlatelet count responseTraditionalMechanism agnostic* 
Benign hematologyPatients with anemia due to (1) chronic kidney disease, (2) chemotherapy-induced anemia, (3) zidoviduine in patients with HIV-infectionHematologic response and reduction in transfusionTraditionalMechanism agnostic* 
Cancer: hematological malignanciesPatients with Acute Lymphoblastic LeukemiaSerum asparaginaseTraditionalAsparagine-specific enzyme 
Cancer: hematological malignanciesPatients with chronic myeloid leukemia; hypereosinophilic syndrome/chronic eosinophilic leukemiaMajor hematologic responseAccelerated/Traditional§               Mechanism agnostic* 
Cancer: solid tumors              Patients with breast cancer; renal cell carcinoma; pancreatic neuroendocrine tumor; soft tissue sarcoma; ovarian, fallopian tube, or primary peritoneal cancer; prostate cancer; thyroid cancer; colorectal cancer; non-small cell lung cancer; head and neck cancer; uberous sclerosis complex; merkel cell carcinoma; basal cell carcinoma; urothelial carcinoma; cervical cancer; endometrial cancer;  hepatocellular carcinoma; fallopian tube cancer; melanoma; astrocytoma; gastrointestinal stromal tumorsProgression free survivial (PFS)     TraditionalMechanism agnostic* 
Cancer: solid tumorsPatients with breast cancer; ovarian cancer; renal cell carcinoma; pancreatic neuroendocrine cancer; colorectal cancer; head and neck cancer; non-small cell lung cancer; small cell lung cancer; melanoma; tuberous sclerosis complex-associated SEGA and renal angiomyoliploma; merkel cell carcinoma; unresectable or metastatic cutaneous basal cell carcinoma; urothelial carcinoma; cervical cancer; endometrial cancer;  hepatocellular carcinoma; fallopian tube cancer; microsatellite instability-high cancer; gastric cancer; thyroid cancer; astrocytoma; AIDS -related Kaposi’s sarcoma; unresectable or metastatic cutaneous squamous cell carcinoma; neurotrophic receptor tyrosine kinase ( NTRK) gene fusion without a known acquired resistance mutationDurable objective overall response rate (ORR)Accelerated/Traditional§               Mechanism agnostic* 
Chronic kidney diseasePatients with chronic kidney disease secondary to multiple etiologiesEstimated glomerular filtration rate or serum creatinineTraditionalMechanism agnostic* 
Cytomegalovirus (CMV)CMV seropositive and hematopoietic transplant recipients requiring prophylaxisPlasma CMV-DNA exceeding threshold for starting treatmentTraditionalAntiviral 
CystinuriaPatients with cystinuriaUrinary cystineTraditionalReducing and complexing thiol 
Cystic fibrosisPatients with cystic fibrosisForced expiratory volume in 1 second (FEV1)TraditionalCystic fibrosis transmembrane conductance regulator potentiator 
Diphtheria vaccine (in combination vaccines)Persons to be immunized against diphtheriaAnti-diphtheria toxoid antibody               TraditionalInduction of immunity 
Duchenne muscular dystrophy (DMD)               Patients with DMD who have aPatients with DMD who have a confirmed mutation of the DMD gene that is amenable to exon 51 skippingSkeletal muscle dystrophinAcceleratedAntisense oligonucleotide 
Fabry diseasePatients with Fabry diseaseHistological reduction of GL-3 inclusion burden in biopsied kidney interstitial capillaries (KIC)AcceleratedEnzyme replacement therapy, chaperone therapy 
Human Immunodeficiency Virus-1 (HIV-1)Patients with HIV-1Undetectable plasma HIV RNATraditionalAntiviral 
Human Immunodeficiency Virus-1 (HIV-1)Patients at high risk of sexually acquired HIV-1Serum HIV antibodyTraditionalAntiviral 
Human PapillomavirusPersons (18 through 45 years of age) to be immunized against human papillomavirusCervical intraepithelial neoplasiaTraditionalInduction of immunity 
Hypercholesterolemia              Patients with heterozygous familial and nonfamilial hypercholesterolemiaSerum LDL-C TraditionalLipid-lowering 
HypertensionPatients with hypertensionBlood pressureTraditionalMechanism agnostic* 
Influenza vaccinePersons to be immunized against influenza Hemagglutination inhibition antibody             AcceleratedInduction of immunity 
Interoperative hemorrhagePatients who require reduction of blood pressure to reduce bleeding during surgeryBlood pressureTraditionalVasodilator 
What is the purpose of the Surrogate Endpoint Table?

FDA’s surrogate endpoint table provides important information for drug developers on endpoints that may be considered and discussed with the FDA for individual development programs.

This table also fulfills a 21st Century Cures Act requirement to publish a list of the  “surrogate endpoints which were the basis of approval or licensure (as applicable) of a drug or a biological product” under both accelerated and traditional approval pathways.

Section 3011 of the 21st Century Cures Act established section 507 of the Federal Food , Drug and Cosmetic Act (FD&C Act), which allows the FDA to provide a list of “surrogate endpoints that were the basis for the approval or licensing (as applicable) of a medication or biological product” under both accelerated and conventional authorisation requirements.

This surrogate endpoint table includes surrogate endpoints that sponsors have used as primary efficacy clinical trial endpoints for approval of new drug applications (NDAs) or biologics license applications (BLAs).  

The table also includes surrogate endpoints that may be appropriate for use as a primary efficacy clinical trial endpoint for drug or biologic approval, although they have not yet been used to support an approved NDA or BLA.
This list facilitates consideration of potential surrogate endpoints when developers are designing their drug development programs. 

What are the key considerations of the surrogate endpoint table?

The table is intended to act as a reference guide to help inform the discussion of potential surrogate endpoints with the related analysis divisions of the Center for Biologics Evaluation and Research (CBER) or the Center for Drug Evaluation and Research (CDER), with the goal of encouraging the production of drugs.

The acceptability of these alternative endpoints should be assessed on a case-by – case basis for use in a particular medication or biological research programme. It is context-dependent, partly depending on the disorder, patient population observed, clinical mode of action and availability of existing therapies.

A particular surrogate endpoint that may be suitable for use in a particular drug or biologic clinical development program, should not be supposed to be appropriate for use in a different program that is in a different clinical setting.

Similarly, composite endpoints with biomarker surrogate endpoints are not used, nor are clinical outcome tests.

If multiple biomarker surrogate endpoints is composed of a single endpoint, the information is included in the table.

Separate adult and pediatric sections are provided.  Pharmacokinetic endpoints that have supported extrapolation from the adults to children are not included in the pediatric section.  

If a surrogate endpoint was previously used to promote accelerated approval of a drug or biologic but subsequent confirmatory trials did not show the predicted therapeutic benefit, the surrogate endpoint would no longer be approved for this use and would not be included on the table.

Other Important facts about Surrogate Endpoints:

A surrogate endpoint is a clinical trial endpoint used as a alternative for a direct measure of how a patient feels, functions, or survives.

A surrogate endpoint does not measure the clinical benefit of the primary interest in and of itself, but rather is expected to predict that clinical benefit.  

Generally, the predictive nature of a surrogate endpoint is determined during the evaluation of epidemiologic, therapeutic, pathophysiologic, or other scientific evidence.

Surrogate endpoints can be characterized by the level of clinical validation:

  • Candidate surrogate endpoint
  • Reasonably likely surrogate endpoint
  • Validated surrogate endpoint

Candidate surrogate endpoints are still under evaluation for their capacity to predict clinical benefit, while validated surrogate endpoints are supported by the clear mechanistic rationale and clinical data providing strong evidence that an effect on surrogate endpoint predicts a specific clinical benefit.”

https://www.fda.gov/drugs/development-resources/surrogate-endpoint-resources-drug-and-biologic-development

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/surrogate-endpoint

https://www.nuventra.com/resources/blog/surrogate-endpoints-benefits-and-criticisms/

https://www.fda.gov/drugs/development-resources/table-surrogate-endpoints-were-basis-drug-approval-or-licensure

Sanofi and Regeneron provide update on Kevzara® in COVID-19 patients

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Sanofi and Regeneron provide update on Kevzara® in COVID-19 patients
July 2, 2020: “Sanofi and Regeneron Pharmaceuticals announced that the U.S. Phase 3 trial of Kevzara® (sarilumab) 400 mg in COVID-19 patients requiring mechanical ventilation did not meet its primary and key secondary endpoints when Kevzara was added to best supportive care compared to best supportive care alone (placebo).

Minor positive trends were observed in the primary pre-specified analysis group (critical patients on Kevzara 400 mg who were mechanically ventilated at baseline) that did not reach statistical significance and these were countered by negative trends in a subgroup of critical patients who were not mechanically ventilated at baseline.

Related News: Sanofi and Regeneron provide an update on U.S. Phase 2/3 adaptive-designed trial of Kevzara® (sarilumab) in hospitalized COVID-19 patients

Sanofi: First patient outside U.S. treated in global Kevzara® (sarilumab) clinical trial program for patients with severe COVID-19

In the primary analysis group, adverse events were experienced by 80% of Kevzara patients and 77% of placebo patients. Serious adverse events that occurred in at least 3% of patients and more frequently among Kevzara patients were multi-organ dysfunction syndrome (6% Kevzara, 5% placebo) and hypotension (4% Kevzara, 3% placebo).

Based on the results, the U.S.-based trial has been stopped, including in a second cohort of patients who received a higher dose of Kevzara (800 mg). Detailed results will be submitted to a peer-reviewed publication later this year.

The primary analysis group included 194 patients who were critically ill with COVID-19 and receiving mechanical ventilation at the time of enrolment.

The primary endpoint assessed the percentage of patients who achieved at least a 1-point change from baseline on a 7-point scale, which consisted of

1) death;
2) hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO);
3) hospitalized, requiring non-invasive ventilation or high flow oxygen devices;
4) hospitalized, requiring supplemental oxygen;
5) hospitalized, not requiring supplemental oxygen – requiring ongoing medical care (COVID-19 related or otherwise);
6) hospitalized, not requiring supplemental oxygen – no longer requires ongoing medical care;
7) discharged from hospital. A second cohort, which was partially recruited (n=27), compared Kevzara 800 mg versus placebo.

The Kevzara trial was designed after a small (n=21), single-arm study in China (Xu et al) among mostly severe, febrile hospitalized COVID-19 patients found elevated IL-6 levels and suggested that inhibiting this pathway with the IL-6 blocker tocilizumab rapidly reduced fever and improved oxygenation in severe patients, allowing for successful hospital discharge.

The Phase 3 Kevzara trial was designed to evaluate this hypothesis in a large, placebo-controlled trial. The trial has been funded in part with federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under OT number: HHSO100201700020C.

A separate Sanofi-led trial outside of the U.S. in hospitalized patients with severe and critical COVID-19 using a different dosing regimen is ongoing.

The same Independent Data Monitoring Committee (IDMC) is overseeing both the Regeneron-led U.S. trial and the Sanofi-led trial outside of U.S., which has recommended that the trial outside of the U.S. continue. The companies expect to report results in Q3 2020.

1: Endpoints  that showed positive trends in patients on mechanical ventilation at baseline, and were countered by negative trends in patients who were not mechanically ventilated at baseline included: the proportion of patients with a 1-point improvement on day 22 (primary endpoint for mechanical ventilation group); the proportion of patients who died by day 29; and proportion of patients who recovered by day 22.

Kevzara® (sarilumab) Injection
Kevzara is currently approved in multiple countries to treat adults with moderately to severely active rheumatoid arthritis who have not responded to or tolerated previous therapy.

Kevzara binds specifically to the IL-6 receptor and has been shown to inhibit IL-6-mediated signaling. IL-6 is an immune system protein produced in increased quantities in patients with rheumatoid arthritis and has been associated with disease activity, joint destruction and other systemic problems.

Kevzara is being investigated for its ability to reduce the overactive inflammatory immune response associated with COVID-19 based on evidence of markedly elevated levels of IL-6 in critically ill patients infected with coronaviruses.

Regeneron Pharmaceuticals, Inc.
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases.

Founded and led for over 30 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to seven FDA-approved treatments and numerous product candidates in development, all of which were homegrown in our laboratories.

Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, infectious diseases and rare diseases.

Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune which uses unique genetically-humanized mice to produce optimized fully-human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.”
http://www.globenewswire.com/news-release/2020/07/02/2057183/0/en/Sanofi-and-Regeneron-provide-update-on-Kevzara-sarilumab-Phase-3-U-S-trial-in-COVID-19-patients.html?print=1

Coronavirus (COVID-19) Update: Daily Roundup July 2, 2020

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Coronavirus (COVID-19) Update: Daily Roundup July 2, 2020

July 02, 2020: The U.S. Food and Drug Administration announced the following actions taken in its ongoing response effort to the COVID-19 pandemic:

  • The U.S. Food and Drug Administration (FDA) issued an updated FDA COVID-19 Response At-A-Glance Summary that provides a quick look at facts, figures, and highlights of the agency’s response efforts.
  • As part of continued action to protect the American public, the FDA is warning consumers and health care professionals about hand sanitizer products that contain methanol (a.k.a. wood alcohol), a substance often used to create fuel and antifreeze.

    Methanol is not an acceptable active ingredient for hand sanitizer products and can be toxic when absorbed through the skin as well as life-threatening when ingested.
    https://lifepronow.com/blog/2020/07/02/coronavirus-covid-19-update-daily-roundup-july-1-2020/
  • The agency has seen an increase in hand sanitizer products that are labeled as containing ethanol (also known as ethyl alcohol) but that have tested positive for methanol contamination.

    State officials have also reported recent adverse events from adults and children ingesting hand sanitizer products contaminated with methanol, including blindness, hospitalizations and death.
  • Testing updates:
    • To date, the FDA has currently authorized 162 tests under EUAs; these include 136 molecular tests, 25 antibody tests, and 1 antigen test.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices.

The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-july-2-2020

FDA Approves New HIV Treatment for Patients With Limited Treatment Options

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FDA Approves New HIV Treatment for Patients With Limited Treatment Options

July 02, 2020: “The U.S. FDA approved Rukobia (fostemsavir), a new type of antiretroviral medication for adults living with HIV who have tried multiple HIV medications and whose HIV infection cannot be successfully treated with other therapies because of resistance, intolerance or safety considerations. 

“This approval marks a new class of antiretroviral medications that may benefit patients who have run out of HIV treatment options,” said Jeff Murray, M.D., deputy director of the Division of Antivirals in the FDA’s Center for Drug Evaluation and Research.

“The availability of new classes of antiretroviral drugs is critical for heavily treatment-experienced patients living with multidrug resistant HIV infection—helping people living with hard-to-treat HIV who are at greater risk for HIV-related complications, to potentially live longer, healthier lives.” 

The safety and efficacy of Rukobia, taken twice daily by mouth, were evaluated in a clinical trial of 371 heavily treatment-experienced adult participants who continued to have high levels of virus (HIV-RNA) in their blood despite being on antiretroviral drugs.

Two hundred seventy-two participants were treated in the main trial arm, and an additional 99 participants received Rukobia in a different arm of the trial.

Most participants had been treated for HIV for more than 15 years (71 percent), had been exposed to five or more different HIV treatment regimens before entering the trial (85 percent) and/or had a history of AIDS (86 percent).

Participants in the main cohort of the trial received either Rukobia or a placebo twice daily for eight days, in addition to their failing antiretroviral regimen.

On the eighth day, participants treated with Rukobia had a significantly greater decrease in levels of HIV-RNA in their blood compared to those taking the placebo. After the eighth day, all participants received Rukobia with other antiretroviral drugs.

After 24 weeks of Rukobia plus other antiretroviral drugs, 53 percent of participants achieved HIV RNA suppression, where levels of HIV were low enough to be considered undetectable.

After 96 weeks, 60 percent of participants continued to have HIV RNA suppression. 

The most common adverse reaction to Rukobia was nausea. Severe adverse reactions included elevations in liver enzymes among participants also infected with hepatitis B or C virus, and changes in the immune system (immune reconstitution syndrome).      

The FDA granted this application Fast Track, Priority Review and Breakthrough Therapy designations. 

The FDA granted approval of Rukobia to ViiV Healthcare.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices.

The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
https://www.fda.gov/news-events/press-announcements/fda-approves-new-hiv-treatment-patients-limited-treatment-options

Informed consent in Clinical Research

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Informed consent in Clinical Research

“Informed consent is the process in which a health care provider educates a patient about the risks, benefits, and alternatives of the given procedure or intervention. The informed consent form must be in patients native language or can be explained for easy understanding.

In general Informed consent requires the patient or responsible party to sign a declaration confirming that they understand the risks and benefits of the procedure or treatment.

The informed consent process means that when you know what to do, the health care provider has sent you specifics about the illness, along with monitoring and recovery choices.

This information can include:
  • The name of your condition
  • The name of the procedure or treatment that the health care provider recommends
  • Risks and benefits of the treatment or procedure
  • Risks and benefits of other options, including not getting the treatment or procedure

    Signing informed consent means
  • You have received all the information from your health care provider regarding your treatment options.
  • You understand the information and you have had a chance to ask questions.
  • Use this information to decide whether you plan to pursue the prescribed care option(s) explained to you.
    You can choose to only provide a portion of the prescribed treatment occasionally. Speak to the clinician about the choices.
  • By signing a consent form, you give your permission (agreement) if you agree to accept any or any of the care services. The submitted and signed form is a formal document that helps the doctor to follow up with the treatment plan.
Clinical Significance

Informed consent is required for many aspects of the health care.

These include consent for:

  • Treatment, 
  • dissemination of patient information, 
  • discussion of HIPPA laws, 
  • specific procedures, 
  • surgery, 
  • blood transfusions, and 
  • anesthesia.  

Obtaining informed consent in medicine is process that should include:
(1) describing the planned intervention,
(2) emphasizing the patient’s role in the decision-making,
(3) discussing alternatives to proposed intervention,
(4) discussing the risks of proposed intervention and
(5) eliciting the patient’s preference (generally by signature). Discussion of all risks is paramount to informed consent in this context.

Most consent covers general risks, procedural-specific risks, no-treatment threats and medication alternatives. In fact, certain consent forms give no guarantees that the planned treatment would include a solution for the issue being discussed.

Protection of patients is a key healthcare priority and successful informed consent is considered a patient safety concern. Recently the Joint Commission discussed the difficulties of maintaining reliable, informed consent.

The emphasis of the patient signature as an indication of the understanding is being called into question. The process of informed consent is shifting to focus more on the communication and less on signatures.

Studies of  the informed consent have found that there are many barriers to obtaining efficient informed consent.

A big hurdle is that for certain people, many consent forms contain wording that is too high a reading standard. The use of multimedia and interactive media devices is promoted to address some of the inefficiencies of the consent process.

Patients should be energetically engaged as a way to enhance communication and ensure patient safety and understanding. 

In emergency cases, informed consent can be withheld where there is insufficient time to seek consent or when the patient is unable to speak and there is no surrogate decision-maker. Not every treatment always includes direct, informed consent.

For example taking a patient’s blood pressure is a part of many medical treatments. on the other hand, a discussion regarding the risks and benefits of using a sphygmomanometer usually is not required.

Clinical Significance in Human Clinical Studies

Informed consent is mandatory for all human-involving clinical trials. The consent procedure must respect the right of the patient to make decisions and adhere to clinical trial guidelines for the particular hospital.

Adherence to the ethical standards in study design and execution is generally monitored by an Institutional Review Board (IRB).

The IRB was founded in the United States in 1974 by the National Research Act, which provided for oversight of human experimentation triggered by controversial testing methods used in the studies on Tuskegee syphillis and others.

Ethical and safe research standards have been an area of the federal and presidential interest since then, with the development of several organizations and task forces since 1974 dedicated to this topic alone.

Valid informed consent for the research must include three major elements:
(1) disclosure of the information,
(2) competency of the patient (or surrogate) to make a decision, and

(3) voluntary nature of the decision. US federal regulations require a full, detailed explanation of the study and its potential risks. 

If such conditions are met an IRB can waive informed consent. Paramount to this is that the subjects in the study are at ‘minimal risk.’ Another definition of reduced risk work is the assessment of action usually found in emergency scenarios.
Examples of this include studying medications used in the emergency room for intubations, or conducting a retrospective chart review.

Changes in informed consent change by FDA during COVID 19

Changes in a protocol are typically not implemented before review and approval by the IRB/IEC, and in some cases, by FDA.

Sponsors and clinical investigators are encouraged to engage with IRBs/IEC as early as possible when urgent or emergent changes to the protocol or informed consent are anticipated as a result of COVID-19.

Such changes to the protocol or investigational plan to minimize or eliminate immediate hazards or to protect the life and well-being of research participants (e.g., to limit exposure to COVID-19) may be implemented without IRB approval or before filing an amendment to the investigational new drug (IND) or investigational device exemption (IDE), but are required to be reported afterwards.

FDA encourages sponsors and investigators to work with their IRBs to prospectively define procedures to prioritize reporting of deviations that may impact the safety of trial participants.”

https://www.fda.gov/media/136238/download

https://www.resuscitationjournal.com/article/S0300-9572(13)00816-2/pdf

https://www.cancer.org/treatment/finding-and-paying-for-treatment/understanding-   financial-and-legal-matters/informed-consent/what-is-informed-consent.html

https://www.ncbi.nlm.nih.gov/books/NBK430827/

https://www.fda.gov/media/136238/download

https://www.fda.gov/media/137496/downloadhttps://www.resuscitationjournal.com/article/S0300-9572(13)00816-2/pdf


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