Adverse drug reactions (ADRs) are a major cause of hospital admissions, with 6.5% due to that cause. Analysis of inpatient stays also shows that 15% of patients experienced one or more ADRs – half of them were definitely or possibly avoidable.
In 1964, the Yellow Card Scheme (YCS) was created to act as an early warning system for unexpected adverse drug reactions (ADRs).
The YCS reporting site allows the submission of reports of suspected adverse reactions to the Medicines and Healthcare Regulatory Agency (MHRA). The MHRA says the system ensures the safe and effective use of medicines, vaccines and medical devices. But does it ensure such safety?
To inform our answer, we searched for publications since 2010 (see here).
The reporting of suspected ADRs by the public is a valuable source of information about the possible harms of pharmaceuticals.
A 2011 health technology review of patient reporting showed that in a two-year (October 2005 to September 2007) period, 5,180 patients and 20,949 healthcare professionals (HCPs) submitted Yellow Card reports.
A questionnaire survey was undertaken among those who did a report, leading to 1,362 evaluable responses. Nearly half learnt about Yellow Card reporting from a pharmacy (49%), followed by their GP (16%).
Most respondents (81%) said the report had been their idea. Forty-three (3.2%) were discouraged by someone from making a report, most by their GP. Fifty-six (4.1%) stated an HCP refused to make a report on their behalf.
Patient reporting of serious ADRs was comparable with healthcare professionals, with a high proportion of patient reports (58%) containing at least one reaction term classified as ‘serious’.
Patients were also more likely to document the impact of ADRs on their lives (47% of patients vs 12% of HCP reports).
A comparison of the ‘patient-only’ with ‘HCP-only’ reports showed that only one in 10 of the YCS reports overlapped. Safety signals generated by patients-only data showed that two-thirds were not in the HCP-only dataset.
One third of respondents expected feedback from the MHRA, and two thirds said they would have liked it. Furthermore, 149 patients wanted to know whether any investigation or action would occur due to their report.
Respondents expected an acknowledgement of their report and information about the reaction, including the frequency of similar reports received, how common the effect was, or whether it was a well-known problem.
Problems with the system
Problems within the system include the inability to distinguish between suspected drug reactions and the underlying condition, impeding the ability to determine signals of harm.
To try and overcome this problem, investigators analyse the proportional reporting ratio (PRR): the spontaneous reporting rate of a particular drug divided by the corresponding proportion for all or several other drugs in the database. This shows whether a given adverse event is reported disproportionately for certain drugs.
The reporting of adverse events can also be assigned causation based on set criteria.
Underreporting
The ability to detect signals and assign causation is hindered by the substantial problems with underreporting of adverse drug reactions. In the U.K., patients have been involved in safety reporting since 2005; however, only one in 12 patients is aware of the possibility of reporting.
A 2006 systematic review of 27 studies reported that underreporting of adverse events was, on average, 94%. It could be as high as 98%, meaning only two in every 100 adverse drug reactions are reported to the MHRA.
This finding is backed by a recent analysis of anticoagulants that compared Yellow Card reports to hospital reports of gastrointestinal bleeds over five years. The North-West of England Hospital Trust recorded 12,013 bleed-related emergency admissions. Of these, 1,058 were taking DOAC anticoagulants. However, only six DOAC Yellow Card reports (0.56% of the possible) were made by the Trust during the period.
In 2018, the MHRA reported that it was “estimated that only 10% of serious reactions and between 2% and 4% of non-serious reactions are reported.”
The Independent Medicines and Medical Device Safety Review (IMMDS; also known as the Cumberlege report) reported gross underreporting with the current system.
The IMMDS recommended that “the spontaneous reporting platform for medicines and devices, the Yellow Card system, needs reform” and that “the MHRA should be required to invite representatives of those who report adverse events (both patients and healthcare professionals) to be involved in evaluating and making decisions on specific safety concerns”.
The IMMDS review showed that patients had been let down and that the reporting problems for devices were, if anything, much worse than for drugs.
The review called for significant reforms at the MHRA due to its mishandling of safety concerns linked to pelvic mesh.
In Europe, EudraVigilance provides online access to suspected side-effect reports. In the U.K., the responsibility falls to the MHRA. The MHRA publishes this information for suspected harms in interactive Drug Analysis Profiles (iDAPs).
They display an overview of all U.K. spontaneous suspected ADRs reported through the Yellow Card Scheme.
However, the system could be more user-friendly and easier to search. For example, medicines are listed alphabetically by the name of the active ingredient, not by the brand name. Clearly, the system for accessing patient information leaflets needs to be better thought through.
As an example, a search for aspirin leads to 7,638 results. Once a disclaimer has been agreed to and ticked, the end user is provided with a bewildering array of choices with documents that are poorly constructed and often impenetrable.
In July 2023 Carl warned MPs that the Yellow Card system should come with a warning:
Professor Carl Heneghan described how under-reporting of adverse drug reactions to the Yellow Card system could be as high as 98%, meaning the ability to detect signals and assign causation is substantially hindered.
The question is whether a system devised 60 years ago is fit for purpose. In the next post in this series, we’ll scrutinise this question further in terms of Covid vaccine data reporting.
Prof. Carl Heneghan is the Oxford Professor of Evidence Based Medicine and Dr. Tom Jefferson is an epidemiologist based in Rome who works with Professor Heneghan on the Cochrane Collaboration. This article was first published on their Substack, Trust The Evidence, which you can subscribe to here.
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It seems to me that as patients have been permitted to report ADRs, the system has given itself permission to ignore them for that very reason. What do the proles know about anything?
Even if only 2% of reactions are reported, it provides a signal that could and should trigger a reaction. And perhaps it did, in the days when I was a GP and not infrequently filled in yellow cards, especially on newer pharmaceuticals that were subsequently withdrawn.
Now the system seems to have succumbed to the norm that “Your feedback is important to us because it enables us to tick the box that we offer feedback.”
Could and should as you say but will not and can not are the reality.
MHRA publicly admitted that between 1% and10% only of ADRs – including fatalities, are reported. So if being generous, multiply by 1- the number of jab deaths. 2,650 I gather – ergo 26k+
Tom and Carl are fantastic ppl but they don’t seem to understand that the actual purpose of the yellow card scheme is to not report adverse events. Remember in this 1984 world in which we live everything is upside down, exhibit A the NHS a place where ppl go to wait for health care rather than actually receiving it. These things are by design not by accident.
WRONG. That’s exactly what they are for
https://journals.rcni.com/nursing-standard/using-the-british-national-formulary-effectively-ns.2016.e10472
https://www.startpage.com/do/search?q=%22British+Pharmacopoeia%22+AND+%22YELLOW+CARDS%22&segment=startpage.brave
No system of reporting is going to be any good if the reports are wilfully and systematically ignored.
My wife, an acupuncturist, worker in a GP surgery in Bath for years. End of the year, Doctor have her his copy of the British Pharmacopeia; it is this that has the Yellow Card reporting tear off pages.
Not ONCE did see one used.
To be fair, the tear-off card was just one source of yellow cards. We had a bundle of the things in a drawer, so that’s where I got mine.
I assume now it’s all done online, but your wife’s experience, like mine, was probably before those enlightened days.