COVID breaks the chain

COVID breaks the chain

“A wise human would have an understanding of the supply chain and how the pieces fit together. But it’s against our nature to think about it. (Paolo Bacigalupi)

There is no denying that the COVID-19 pandemic has ravaged the globe, leaving in its wake death and severely ill patients. The novelty of this virus and the speed of its spread have meant there is no specialised cure. Instead, health professionals and pharma companies alike have struggled to repurpose existing drugs in an attempt to treat those that have contracted the disease.

This has resulted in many countries having to break from the authorised prescribing practices in their efforts to find a drug or combination of drugs to defeat the virus or treat its varied symptoms.

From a pharmacovigilance perspective, this unique situation presents many opportunities that could result in a reduction in patient safety. To ensure this does not happen, major regulatory authorities including the FDA, the UK MRHA and the EMA have revised guidelines, set up special reporting websites and pleaded for all and any, valid or suspect, adverse events to be reported, particularly related to COVID-19 treatments.

So – while the regulatory authorities are encouraging patients and healthcare practitioners to be vigilant with safety related to COVID-19, there is also a growing concern for safety issues relating to continuity of treatments for conditions not related to COVID-19. These concerns stem from:

  • the interruption in the supply chain for Active Pharmaceutical Ingredients (APIs) and manufactured novel and generic drugs
  • the unfounded fear that certain medications for cardiovascular and rheumatic diseases could increase the chances of contracting COVID-19.

There is a strong possibility that the financial burden forced on healthcare systems caused by the COVID-19 pandemic will increase prescription of generic rather than branded drugs in an attempt to cut costs and contain budgets.

The irony is that the enforced boarder closures and the prolonged lockdowns first in China and then in India has had a huge impact on the ability of these two dominant countries to produce and distribute both generic agents and the APIs they are manufactured from. China and India are responsible for more than 80% of the APIs used to make drugs sold in Europe; together they host 31% of the world’s FDA-registered API-manufacturing plants. Furthermore, India supplies 40% of the World’s generic drugs, and before it was affected by the pandemic, was making strides to increase its API-manufacturing capacity to become less reliant on China for its chemical supplies.

The reality that the world is majorly reliant on two countries for its ability to provide pharmaceuticals is a concern, especially when we see how quickly the supply chains were impacted by enforced lockdowns.

Interestingly, even before the outbreak of COVID-19, Europe was keen to bring back drug manufacturing to its home lands so not to rely so heavily on imported materials. In the US, however, the concept of drugs made in America is being met with some resistance. Perhaps the huge disruption COVID-19 has had in terms of being able to heal and protect ourselves, maybe the catalyst required to rethink the concept of putting all our drugs in one basket.

With respect to generics, there is a misconception that they do not “work the same way” as branded medicines. Small molecule generics need only demonstrate bioequivalence to a reference product within an accepted 80%-125% margin of difference; generic agents do not have to demonstrate bioequivalence with each other. There is a concern two generic agents can legitimately have a 45% difference in their bioavailabilities. However, the FDA has stated over a 12-year period the average difference in drug absorption between branded and generic agents was 3.5%.

Adverse events occurring in patients switching to, or between generic agents is not unheard of, and in some cases it is the excipients and bulking agents that are the culprits. In an attempt to avoid drug shortages, some countries have changed to prescribing practices permitting only one instead of three months’ supply. This could result in more frequent “generic swapping”, particularly as the duration of the pandemic extends. If this happens, we must rely on patients and healthcare practitioners to report their experiences. And for generic manufacturers extra vigilance regarding literature monitoring is prudent since generic products may be more frequently prescribed than before.

It is not only generic drugs per se that may be cause for concern. The FDA recently highlighted the importance of drug packaging in terms of safe use. In response to a shortage of a neuromuscular blocking agent, required for intubation of COVID-19 patients, the temporary production of a similar drug was permitted without the usual warnings on the bottles. Although the two contain the same active ingredient, Propoven 2% (the drug under EUA) is double the concentration of the FDA-authorised Diprivan; the lack of warnings could lead to accidental overdose if practitioners are not aware of the temporary replacement.

I believe that, especially in the wake of the COVID-19 pandemic, “pharmaco-extra-vigilance” practices are necessary regarding literature monitoring to ensure all safety events, particularly those categorised as special situations, are captured. Not only for drugs directly involved in the treatment of the virus and its pathological symptoms, but also for branded and generic drugs that will have been impacted by the global disruptions in the supply chains resulting from the waves of lockdown that have swept the globe.

Image by Shaojie on Unsplash.

COVID causes chaos and special situations

COVID causes chaos and special situations

“Order brings sameness. Chaos brings newness every moment. The problem is first overcoming our fear of chaos, and then mining for the great ideas and bringing them back home.” (anon.)

Since the start of 2020, and the dawning realisation that something was “not quite right” with the world, chaos has indeed reigned. Bringing with it fear, not only of the chaos, but also of the cause….the novel coronavirus SARS-CoV-2 (COVID)

The COVID-19 pandemic has necessitated the unprecedented use of a number of pharmaceutical agents not only in an attempt to find an effective treatment for the viral infection itself, but also to manage the severe and varied nature of the symptoms associated with this deadly virus.

This has resulted in an increase in the number of (often emergency) situations where drugs have been used off-label and/or resulted in cases of pregnancy exposure or lack of efficacy. From a pharmacovigilance perspective, these “special situations” must be closely monitored to ensure the emerging safety information relating to the use of drugs in such cases, is appropriately recorded and analysed so that subsequent interventions can happen to ultimately guarantee patient safety.

From our experience, the proportion of special situations identified in the literature is approximately 15% of Individual Case Safety studies (ICSRs) reported. During the first half of 2020, the proportion of special situations associated with COVID-19-related drug use has increased by a further 10%…. and this is only the beginning.

Unfortunately, while the virus has increased the number of drug safety events worldwide, it has simultaneously reduced the resource and potential to record what will become an important phase in the history of global drug safety.

This was recognised by the US FDA when it recently updated its guideline related to post-marketing adverse event reporting during a pandemic.

To ensure that safety data related to medicinal use during the COVID-19 pandemic are captured, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) has set up a designated website, and the EMA has taken a similar approach with its call to action for all patients with COVID-19 to report any adverse events relating to the use of medicinal products they may receive, since it is important to understand the potential drug interactions that patients may experience.

These data-capturing processes are essential in the current “trial and error” situation we find ourselves in. The need for close monitoring of off-label use of drugs is imperative, now more than usual, if industry is to ensure patient safety in the search for the most effective treatment in the absence of a purpose built cure.

This agile approach has been demonstrated by the FDA when it issued two Emergency Use Authorisations (EUAs) for off label use of Remdesvir and also for chloroquine phosphate and hydroxychloroquine sulfate; then, just 11 weeks later, the EUA for chloroquine and hydroxychloroquine was revoked, based on on-going gathering of evidence that indicated these agents may not be effective for the treatment of COVID-19.

Use of azithromycin to protect healthcare workers from the virus was fleetingly entertained in the UK; this glimmer of hope was short lived as evidence emerged to indicate azithromycin was not effective and may have an unfavourable risk-benefit profile especially when given in combination with hydroxychloroquine. This was supported by National Institutes of Health that issued guidelines strongly recommending against the combined use of hydroxychloroquine plus azithromycin, citing potential toxicities, and also against the use of HIV protease inhibitors without evidence of clinical benefit against the disease. Although disappointing, this information is important for patient safety, and in terms of pharmacovogliance the lack of efficacy observed with these and other repurposed drugs will contribute to the growing volume of valuable safety literature.

At the beginning of 2020 an increase in special situation literature safety reports began to emerge as the pandemic swept the globe and the world looked for an effective treatment for this disease. A search of the AdisInsight Safety database confirms that off-label use of lopinavir and ritonavir, alone and combination was associated with adverse events in patients located in China, Japan, Poland France Iran and the US. And pregnancy exposure, to a variety of drugs, was evident particularly in China and the US.

With the unfortunate possibility that we will experience a second wave of COVID-19 infections in countries that seem to have already conquered the disease, hopefully we can learn from the safety information generated during the initial wave and can put it to good use.

The global impact this disease has had on the use of pharmaceutical products is yet to be fully realised. I believe that the volume of safety-related literature is set to soar over the next few years as the information regarding this unique situation is processed and published.

Image: Morning Brew on Unsplash.

Call for Papers – The Patient

Call for Papers – The Patient

COVID-19 Health Preference Research (HPR)

The Patient invites the submission of health preference studies for a themed issue on coronavirus disease 2019 (COVID-19) to be published early 2021 and guest-edited by Rachael DiSantostefano (Janssen) and Fern Terris-Prestholt (LSHTM). We encourage papers from multiple perspectives and on a range of topics, such as preventive behaviours, interventions, and policies related to COVID-19.  For example, a study may test the causal relationship between vaccine attributes and uptake or predict heterogeneous behaviours within a population to inform regulatory decisions, economic evaluations, clinical practice, and health policy. Due to the urgency of the ongoing pandemic, submissions exploring preferences from those based across the globe with clear relevance for COVID-19 patients and caregivers are particularly welcome.

Like the rest of the world, the pandemic has reshaped the lives and livelihoods of scientists in HPR. Many investigators reacted by conducting empirical COVID-19 studies to better understand the value of health and health-related alternatives. This call for papers was motivated by the June COVID-19 HPR Roundtable, a monthly open meeting of HPR scientists exchanging ideas and lessons learned.  Participation in the Roundtable is encouraged, but not required to submit for this call.

Topics of interest include preferences for:

  • Public health initiatives
  • Screening and testing
  • Prevention, such as vaccines, masks, and health behaviours
  • Pharmacological and non-pharmacological interventions
  • Resource allocations
  • Health outcomes, including health-related quality of life
  • Labor conditions, productivity, and workplace safety

Please submit a full paper by November 30th, 2020, to chris.carswell@springer.com. For this themed issue, a dedicated panel of reviewers will be assembled, so that the editors receive their reports promptly and can respond to authors quickly, expediting the publication of timely evidence in early 2021.

The Patient is an official journal of the International Academy of Health Preference Research and is published by Springer Nature. It is indexed in all major databases and has an Impact Factor of 3.2. Further journal metrics can be found here https://www.springer.com/journal/40271

Invitation to Contribute to a Themed Issue on “Big Data and its Application to Public Health Decision Making”

Invitation to Contribute to a Themed Issue on “Big Data and its Application to Public Health Decision Making”

PharmacoEconomics announces a themed issue on big data analytics and its application to healthcare decision making, with a focus on health economics and outcomes research (HEOR).  The purpose of this themed issue is to showcase the application of big data analytics and HEOR concepts in healthcare decision making.  This issue will become a valuable source of innovative real-world applications of HEOR methods and big data analytics (including artificial intelligence and machine learning methods).

This Call for Papers arose out of the growing international demand for real-world evidence and increased use of HEOR concepts in healthcare decision making, together with sustained international interest in big data. The demand for real world evidence is being met by using HEOR tools and big data analytics. We seek to highlight these efforts. Thus, this Call for Papers invites applied papers that lie at the intersection of HEOR, big data analytics, and healthcare decision making. We welcome contributions from diverse international decision contexts including decision making for individuals at high risk for poor health outcomes, uninsured/low income/difficult-to-reach populations, or health disparity populations.

Given the purpose of this themed issue, we will consider only applied papers. It is important that the papers present a clear, accessible discussion that would engage researchers unfamiliar with the decision context.  Each submitted paper should accomplish the following objectives: 1) place the paper at the intersection of big data, HEOR, and healthcare decision making; 2) provide a well-balanced discussion of the real-world implications of their findings; 3) discuss how the paper supports the field of HEOR in harnessing the availability of big data.

Priority will be given to papers that illustrate the use of big data analytics and HEOR concepts in real-world decision making. We will consider papers in any of the following categories as they relate to decision making:

I.  Emerging Methods of Analysis
II.  Data Quality Issues
III.  Data Linkages
IV.  Health Information Technology
V.  Translating Evidence from Prior Studies

If you would like to contribute to one of these themes, please submit an abstract of up to 400 words by 31st July 2020 to chris.carswell@springer.com . Authors of selected abstracts will be notified by the end of August 2020 and asked to submit their final manuscript by 31st October 2020.

Eberechukwu Onukwugha

Guest Editor

Christopher Carswell

Editor in Chief

PharmacoEconomics

The future has arrived – report from the DIA PVRMS Conference 2020

The future has arrived – report from the DIA PVRMS Conference 2020

What struck me most about many of the presentations at the recent DIA Pharmacovigilance and Risk Management Strategies conference (27-29 January in Washington DC) was that the future is already here, because change is already happening. For the last 2-3 years, many sessions at PV conferences focused on the potential of game-changers such as artificial intelligence, real-world evidence, personalised medicine and social media: Can we utilise these? What role do they play? Are they effective? It seems that the time is now for such concepts to be embraced by the industry and regulators alike in the pharmacovigilance world. And all of this against the backdrop of Brexit coming to fruition. Continue reading “The future has arrived – report from the DIA PVRMS Conference 2020”

Call for Papers – PharmacoEconomics

Call for Papers – PharmacoEconomics

Economic Consequences of Major Depressive Disorder

PharmacoEconomics invites the submission of papers (original research, reviews, opinion and tutorial pieces) on the economic consequences of major depressive disorder (MDD) for a themed issue of the journal to be published in 2021 and guest edited by Paul Greenberg (Analysis Group). We encourage papers from the perspectives from a variety of stakeholders including payers, health technology assessment bodies, health economists, clinicians, pharmaceutical industry, policy makers, patients and caregivers, and advocacy groups. Special patient population perspectives (e.g. youth, comorbid populations, aged) and papers employing novel methods are particularly encouraged. Papers can be either methodological or applied.

Topics of interest include:

  • Epidemiologic estimates of MDD and its treatment
  • Economic and Humanistic Burden
    • Direct and indirect costs
    • Employment effects
    • Spillover effects
    • Quality of Life
  • Cost Effectiveness of Treatment
    • Models, trials or database analyses
  • Stated Preferences
    • Discrete choice experiments
    • Utility estimation
  • Methodological Challenges
    • Special patient populations
    • Impact of adherence
    • Modelling (treatment sequences, combination treatment, defining health states)
    • Challenges in conducting database analyses
    • Estimating workplace burden
    • Precision medicine
    • Placebo effects
    • Behavioural interventions
    • Treatment adverse effects
    • Distinguishing PRO and QALY data from data gathered using diagnostic instruments

Please submit an abstract describing your proposed paper by June 30th, 2020 to chris.carswell@springer.com. Full papers will be invited by July 31st 2020 and manuscripts due by November 30th 2020

Reactions Weekly: Introducing New Features for 2020

Reactions Weekly: Introducing New Features for 2020

From January 2020, Reactions Weekly (https://link.springer.com/journal/40278) – an Adis newsletter – will have a new focus and features.

Reactions Weekly provides readers with the latest and most important news and research relating to drug safety. It has published drug safety news for almost 40 years, producing over 1700 issues. It offers readers a significant saving in the time and effort required to research and keep up to date with the thousands of information sources reporting drug safety information. This information is provided in a concise and convenient weekly update.

Over time, it has become increasingly challenging to find relevant drug safety information in Reactions Weekly because of our focus on providing extensive coverage of the large volume of articles published in the biomedical literature. Therefore, we are introducing changes to the content of Reactions Weekly from 2020 to streamline the product and improve the reader experience.

The changes we are introducing will focus the content on the most clinically important adverse reaction news of significance to healthcare practitioners, researchers and regulators. The new features will increase our coverage of drug safety research, simplify the presentation of case report articles, and improve the ability to identify key data at a glance.

Specifically, the changes include:

  • To increase our coverage of drug safety research, there will be a table of additional drug safety news articles relevant to our readers (see example 1).
  • To streamline the presentation of case report articles, author comments and reporter country will be removed to focus on the most relevant information for our target readers.
  • To make it easy to identify the key data at a glance, non-serious case reports will be presented in a table rather than as individual articles (see example 2).

We look forward to presenting the new features to you in 2020. If you have any questions, please contact Pauline.mcwilliams@springer.com.

Photo credit: Photo by pina messina on Unsplash

Other

Non-serious

AdisInsight strikes again with global, drug-centric patent data

AdisInsight strikes again with global, drug-centric patent data

Year after year our customer research has indicated that end users needed more information about the patent protection for the drugs they were analyzing with AdisInsight.  They wanted to answer questions like when a generic version of a branded drug will be available, which countries are covered and not covered by patent protection, and what patent extension strategies are available to prolong market exclusivity. We studied the current user journeys of our users and found they almost always ended with an expert patent searcher or patent attorney searching one of the existing patent databases because these complex resources require special skill to use them correctly.

In 2017 we set out to enhance the patent information available in AdisInsight. We conceived of a simple and intuitive tool that would allow our users to discover patent information themselves in order to inform strategic decisions.  This would translate into quicker answers and use fewer resources compared to their current approach involving patent attorneys directly.  We had tried this many times before only to find the task of grouping the patents pertaining to a specific drug too difficult. This time our content development team identified and evaluated several potential partners who could provide drug-based patent information. Think BioTech rose to the top due to their ability to associate patents with the specific drugs they apply to.  At the end of 2017 a partnership agreement was reached with Think BioTech (click here to read the press release) to supply AdisInsight with patent content for marketed drugs.

Once the agreement with Think BioTech was in place, stakeholders from product management, content development, IT&P, UX design, and IT developers came together to create the product vision for AdisInsight Patents, mock-up how patent information would be displayed to meet the needs of end users, and develop a plan to implement our MVP.

In March 2018 I went on the road with our lead UX designer, our business analyst, and one of my product manager for AdisInsight to conduct User Experience testing to validate the designs developed met customer needs. We conducted 13 end user interviews across pharma, biotech, and consulting. The results showed that our design placing an emphasis on displaying specific formulations of a drug missed the mark. In true agile form we rapidly arranged another stakeholder meeting to digest the UX findings and pivot our design.

The first iteration of the AdisInsight Patents module was made available to customers on August 31, 2018.  It provided patent information for specific drugs organised in separate Drug Patent Profiles.  Each Drug Patent Profile summarizes the key information from global patents and regional exclusivities protecting that specific drug and presents key information such as patent number, expiry date, claim type and country in easy to read tables allowing users to visualize the protection landscape globally.  Subsequently enhancements were added to AdisInsight Patents to satisfy additional user needs.  Adis Patent Detail Sheets were added to present key information about a specific patent such as title, abstract, inventors, assignee, application number, source, and claim details.  This allowed users to drill down from the Drug Patent Profile to get more information about a specific patent protecting the drug they are investigating.  Later link to the source document at the United States Patent and Trademark Office website or the World Intellectual Property Organization website were added to allow the user to click through to the source patent document.

The intuitive AdisInsight search interface makes identifying patent information easy for users.  The new AdisInsight Patents module utilizes the same familiar search terms such as drug name, indication, mechanism of action, drug class, formulation, location and company used throughout all of the AdisInsight modules.  These powerful search terms are enabled through manual indexing using controlled vocabularies and synonyms.  This produces highly precise search results and minimal noise, especially when compared to free text or Google-like searching.

It has been a very interesting journey. One that ultimately led to a patent product that is proving valuable for our end users as they work to develop better drugs to treat disease.  But this is just the start of the journey we will continue to add more content and more functionality to AdisInsight in the months to come.

Call for Papers – The Patient

Themed Issue – Patient and Public Involvement in
Health Economics Research (HEOR)

The disability movement first coined the phrase “Nothing about us without us” in the 1990s. Since then, the idea has widened and public and patient involvement (PPI) in health research has grown to be the norm.  Patients and the public are no longer merely subjects or recipients of health economics and outcomes research (HEOR), we are now engaging with them as active research partners and collaborators, including as co-investigators and co-authors. 

The Patient invites the submission of papers (original research, reviews and commentaries) on the role of patients and the general public in HEOR for a themed issue of the journal to be published in early 2020, guest edited by Paula Lorgelly (King’s College London).

We encourage papers that highlight innovative ways researchers have engaged patients and/or the public, projects that have trained patients/the public in order to increase their understanding of HEOR, and papers that have measured and quantified the value of patient/public engagement to their project. Country-specific perspectives are also encouraged particularly given that different funding bodies have varying requirements and standards regarding PPI. Papers can be either methodological or applied. Article types can be original research, thought pieces or reviews.

Topics of interest include:

  • Patients and the public as collaborators, including generating research questions
  • Patients and the public as trialists or modellers, i.e. designing methods
  • Training patients and the public to increase/improve their value to projects
  • Comparison of different engagement approaches, including PPI in HEOR projects vs other types of studies
  • Comparisons of projects involving patients versus those involving the public
  • Lay patients vs professional patients
  • The role of patient groups and/or research charities
  • PPI and conflicts of interest
  • Risks and benefits of greater PPI in HEOR

Note we are specifically interested in the role of patients and the public in HEOR; papers either on PPI in funding decisions (for research funding or technology adoption) or on outcome measures that are not preference based or use patient values  while of interest to the journal are outside of the scope of this themed issue.

Please submit an abstract describing your proposed paper by 31st August 2019 to chris.carswell@springer.com. Full papers will be invited by 30th September 2019 and manuscripts due early 2020.

Safety strategies and efficiencies – what is the best solution?

Safety strategies and efficiencies – what is the best solution?

This was the subject of many discussions at the recent World Drug Safety Congress Americas 2019 in Philadelphia. As has been the case at many pharmacovigilance meetings in the last few years, artificial intelligence, outsourcing solutions and automation were hot topics, with debates over the future use of such strategies to achieve operational efficiency whilst strengthening patient safety. Continue reading “Safety strategies and efficiencies – what is the best solution?”