Call for Papers – Drug Safety

Call for Papers – Drug Safety

Drug Safety invites the submission of original research articles (up to 6000 words) on the Role of Artificial Intelligence/Machine Learning in Pharmacovigilance for a themed issue of the journal to be published in 2021. The issue is guest edited by Dr. Andrew Bate (GSK) and Dr. Yuan Luo (Northwestern University). With a mix of invited review articles and original research articles, the theme issue will provide a comprehensive coverage of how emerging technologies can affect work tasks and further improve the field of pharmacovigilance.

We welcome proposals for original research articles on the following topics:

  • Methods for identifying safety signals in any or combinations of data source

Author Brief: The article will showcase novel research on how pharmacovigilance can benefit from the continuously increasing number and form of data sources, especially electronic health record data and patient self-tracked/self-collected data. In addition, the article will discuss how machine learning has helped improve identifying safety signals from these data sources for pharmacovigilance.

  • Prediction, in future numbers of adverse events or types of safety outcomes, or change in severity in RCT, PSPs, RWD or other data sources e.g. prospective surveys

Author Brief: The article will showcase novel machine learning methods for predicting outcomes such as future numbers of adverse events or types of safety events, or change in severity in randomized controlled trials (RCTs), patient support programs (PSPs), real world data (RWD) or other data sources e.g. prospective surveys. Of particular interests is how the methods will account for longitudinality and missing data from the above data sources for pharmacovigilance prediction.

  •  Visual pattern recognition in safety

Author Brief: This article will describe the novel application of visual pattern recognition to support signal detection in pharmacovigilance.

  • Developing test sets for assessing machine learning algorithmic performance

Author Brief: The article will showcase efforts for developing test datasets for assessing machine learning performance in pharmacovigilance tasks such as predicting future numbers of adverse events or types of safety events. The article will need to demonstrate rigorous annotation process e.g., inter-annotator agreement evaluation and quality control. Of particular interests is the actual release of a  dataset for pharmacovigilance prediction.

  • Developing frameworks for increasing transparency or explainability of machine learning outputs (including visualization) as well as assessing how to best implement into routine use

Author Brief: The article will showcase efforts for developing novel methods to assess and ideally increase the transparency of machine learning models in predicting pharmacovigilance outcomes either at systemic cohort level or at individual patient level. Adoption and/or implementation of such efforts in real world pharmacovigilance is a plus. Integration of multiple data sources to collate on each other and improve transparency is also a plus. Of particular interests is the open-source release of such a system.

  • Methods work in building capabilities to facilitate case processing and intake

Author Brief: Both regulators and pharmaceutical companies have very complex processes with many steps to get reports into their databases. The article will focus on robotic process automation and machine learning-based approaches to make report entry more efficient and effective.

  • Approaches for assessing quality, reliability, credibility and trust in machine learning outputs

Author Brief: The article will showcase efforts for evaluating quality and reproducibility of machine learning models in predicting pharmacovigilance outcomes either at systemic cohort level or at individual patient level. Evaluation on a large multi-institute dataset is ideal. Detailed error analysis on generalizability and reproducibility is a plus. Of particular interests is the open-source release of such a system to establish some “industrial standard”.

Please submit an abstract describing your proposed paper by 30 April 2021 to nitin.joshi@springer.com. Full papers will be invited by 30 May 2021 and manuscripts due by 31 August 2020.

Drug Safety is the official journal of the International Society of Pharmacovigilance (ISoP) and is indexed in all major databases. It is published by Springer Nature under the Adis imprint.

World Drug Safety Congress Americas 2020: my first virtual conference experience

World Drug Safety Congress Americas 2020: my first virtual conference experience

Last month I “virtually” attended the World Drug Safety Congress on September 2-3, 2020 on behalf of Adis Pharmacovigilance.   Originally scheduled as an in-person conference for March 24 – 25, 2020, due to COVID19, it was rescheduled as a virtual conference in September 2020. 

Continue reading “World Drug Safety Congress Americas 2020: my first virtual conference experience”

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.

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”

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?”

DIA India 2019: Regulatory Trends in Clinical Safety & Pharmacovigilance (An EU perspective).

DIA India 2019: Regulatory Trends in Clinical Safety & Pharmacovigilance (An EU perspective).

This first session of the conference, chaired by J Vijay Venkatraman, gave the audience a broad overview of the state of flux in pharmacovigilance, essentially resulting from changes initiated in Europe – the impact of evolving Eudrovigilance, Brexit and E2B R3 were the focal points. Continue reading “DIA India 2019: Regulatory Trends in Clinical Safety & Pharmacovigilance (An EU perspective).”

Planning and strategizing in the face of evolving regulatory guidelines: Report from the DIA Pharmacovigilance and Risk Management Strategies Conference (PVRMS19)

Planning and strategizing in the face of evolving regulatory guidelines: Report from the DIA Pharmacovigilance and Risk Management Strategies Conference (PVRMS19)

The PVRMS19 was presented at the Omni Shoreham Hotel, Washington DC, January 2019. During the packed three-day event, we learned that many aspect governing the development and subsequent safe and effective use of medicines are in a state of flux… and so they should be. As we learn by our actions (triumphs and failures) we make adjustments to enhance the future investigations and create medicinal agents that are effective and safe, or more precisely, have a benefit that outweighs the risks. Continue reading “Planning and strategizing in the face of evolving regulatory guidelines: Report from the DIA Pharmacovigilance and Risk Management Strategies Conference (PVRMS19)”

Pharmacovigilance in the Middle East: Adis PV attends the regional ISoP meeting

Pharmacovigilance in the Middle East: Adis PV attends the regional ISoP meeting

Springer Nature sponsored the annual meeting of the International Society of Pharmacovigilance (ISoP) Middle East Chapter under the Adis Pharmacovigilance brand, held on the 20th of September 2018 in Dubai. ISoP is an international non-profit organisation which aims to promote pharmacovigilance and enhance the safety and proper use of drugs worldwide. Continue reading “Pharmacovigilance in the Middle East: Adis PV attends the regional ISoP meeting”

The World Drug Safety Congress in Amsterdam addresses key challenges

The World Drug Safety Congress in Amsterdam addresses key challenges

Adis Pharmacovigilance attended the World Drug Safety Congress in Amsterdam on Sept 10th and 11th.

The event has been running for over a decade and is world renowned for its ability to connect key stakeholders in the drug safety field, as well as for leading the way in moving the sector forward.

Senior level drug safety professionals, as well as representatives from sponsors and service providers, met to discuss key topics and showcase solutions.

This year’s theme, Addressing Key Challenges for Safety Professionals, had us prepared for a series of interesting presentations and discussions on the ever growing importance of pharmacovigilance and the challenges connected with ensuring patient safety. Continue reading “The World Drug Safety Congress in Amsterdam addresses key challenges”