Pharmacovigilance – The importance of translation for patient safety

It’s a fact that most medical products – in addition to the benefits, cures, and relief they bring – also come with some side effects, known or unknown.

The clinical trial phase of a drug is an essential testing ground for the detection of these side effects. During a trial, reactions are reported and analyzed, predisposing factors are identified, and findings are provided as part of marketing authorization applications and in prescribing information.

The clinical trial process, however, for all its rigor, has limitations. During a trial, a drug is tested on a relatively small group of people and over a set period of time. As we have discussed elsewhere, it’s often the case that participation in clinical trials is not representative of diverse, real-world populations, not to mention that certain groups are routinely excluded by design (e.g. pregnant people, those with pre-existing conditions, older people, etc.) As such, it’s borderline inevitable that some side effects will only occur after the point of trial, when the drug in question is in use in a broader population and over a longer duration.

What is Pharmacovigilance?

Pharmacovigilance (PV) refers to the ongoing efforts to monitor, assess, and address patient safety, adverse events (AEs), and adverse drug reactions (ADRs) after a drug has been introduced to the market. For PV to be successful, it must involve all stakeholders, from patients and users, to healthcare professionals, pharmaceutical companies, and regulatory authorities. And it should monitor the product throughout its lifecycle – usually over the course of years – continuously assessing and balancing its benefits against its risks.

So, where does translation fit into what sounds like a pretty technical, medical process? The honest answer is – everywhere! But let’s start at the start. And, in terms of pharmacovigilance, the “start” is to prevent AEs happening in the first place. Translation has an essential role to play in this, as clear, effective communication (i.e. in a language and at a level understood by the reader) means better adherence. That is to say, patients who fully understand the instructions associated with a drug are much more likely to follow those instructions correctly, reducing the instances of AE associated with incorrect usage. From a language perspective, there are around 25 million people in the US who are considered to possess limited English proficiency (LEP), while 57 million people (20% of the US population) speak a language other than English at home.[1] Meanwhile, 59% of AEs reported can be traced back to communication issues[2], and the majority of these are experienced by LEP patients. These patients are also more likely to suffer serious harm as a result. As for the 20% of the population who do not speak English at home, it’s not particularly controversial to say that someone who speaks English as a second language may have skills perfectly adequate for day-to-day life but not at the level necessary for a high-stakes medical context. For these 2 categories of patient, then, translated communication is absolutely key, as is the quality of that translation.

What about the issues we can’t prevent?

Although clear communication helps reduce them, a certain number of AEs are going to happen with any drug in the market. (We refer you back to our points above regarding the limitations of clinical trials.) And these AEs need to be reported in order to assess for real risk and to keep people safe. The number of reports coming through each year can be significant, with some more common products receiving in excess of 1,000![3] There are suggestions in the research we have already mentioned, however, that linguistic and cultural factors may lead to lower instances of this reporting among LEP patients. If true, this would perpetuate the data biases we already see at the trial stage (the exact biases PV is at least partially intended to redress)! Clearly, translation can assist here, by localizing for language and culture, and smoothing the pathways of communication between patient and healthcare provider; healthcare provider and pharmaceutical company. Almost as important as the existence and quality of this translation is the speed at which it is completed. Some regulatory bodies mandate official reporting of certain AEs within as little as a week of initial notification.[4] More importantly, delays in communicating genuine ADRs can have ramifications for individuals’ health and can also impede producers’ ability to get ahead of a potential crisis.

What constitutes a crisis?

Generally speaking, the process of detecting signals and assessing for ADRs is meticulously slow and carried out over the long term. At times, however, this process must be hugely compressed to deal with a crisis. A crisis can be brought about in a number of ways, and for a number of reasons. It could be due to instances of fatal or severe ADRs, as the result of world events, or because of the actions of an influential body or individual. Recent history, unfortunately, offers ample examples of PV crisis situations and communications. Of course, we’re referring primarily to the real-time chaos of the COVID-19 pandemic, and the rumors and misinformation that were rife during that time.

Take, for example, former US President, Donald Trump’s, comments regarding hydroxychloroquine. Statements about the anti-malaria drug’s (unproven) effectiveness against COVID-19 necessitated immediate crisis management in 2020, given its known side effects on heart rhythm. Or what about the hugely inflated news of AstraZeneca’s Covid vaccine causing blood clots, which has been shown to have gained significantly more traction in some languages and among some groups than others.[5] Or look at the anti-vaccine movement popular during this time period.

This is all a stark example of the value of clear communication which is targeted differently for different communities. (And of the ramifications of failure in this regard.) Even when the science is clear, perception is subjective, and “may be related to fear, beliefs, and previous experiences”[6]. So, communicating in a clear, informed, and culturally empathetic way can be the difference between adherence and utter refusal in great swathes of a population, as we have so recently seen. As the WHO put it, failure to communicate well can “lead to a loss of trust and reputation, economic impacts, and − in the worst case – loss of lives”.[7] If communications regarding the safety of the AstraZeneca vaccine had been faster and more targeted in the French-speaking community, what impact might that have had on the uptake of that vaccine in France? If information about the benefits, testing, and safety of vaccines in general had been better disseminated to e.g. the Bangladeshi community in the UK[8], what effect could that have had on the spiraling infection rates in the country at the time?

In extreme situations, poor communication (especially in the face of rumors or misinformation) can even result in mass hysteria and civil unrest, as seen during Ghana’s deworming campaign in 2007.[9] In the latter case, crisis communications were handled sensitively and amplified widely by bodies and publications the population trusted, in language they were accustomed to, which rapidly de-escalated the crisis. It’s clear to see, in cases like these, how much of a difference engaging, convincing, localized communications can make in reassuring disparate groups of people about the safety of something we all hold very dear – our health and the health of those we care about.

Given the broad spread of locations, uses, and groups that fall within PV’s remit, it’s obvious that pharmacovigilance and translation necessarily go hand in hand. If you would like more information on how translation can improve your pharmacovigilance activities, patient safety, and crisis communications, please contact the Conversis team. We would be delighted to work with you to help keep all your patients safe.

[1] https://www.ahrq.gov/sites/default/files/publications/files/lepguide.pdf

[2]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111827

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873545/

[4] https://www.fda.gov/drugs/investigational-new-drug-ind-application/ind-application-reporting-safety-reports

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10301370/

[6] As above

[7] https://iris.who.int/bitstream/handle/10665/331513/WHO-2019-nCoV-RCCE-2020.2-eng.pdf?sequence=1

[8] https://www.england.nhs.uk/south-east/wp-content/uploads/sites/45/2021/05/Vaccination-and-race-religion-and-belief-A4.pdf

[9] https://www.thelancet.com/journals/lancet/article/PIIS0140673607612112/fulltext