FOI release

Freedom of Information request about adverse drug reactions (ADR) (FOI-21-313)

Published 28 May 2021

Thank you for your FOI request dated 29th March 2020, where you requested the following information:

“Please could you tell me the total number of adverse drug reactions (ADRs) reported to you through the Yellow Card scheme in the 2020 calendar year? In relation to the figures for 2020 could you also provide (i) the number of UK suspected ADR reports received with a fatal outcome, (ii) number of ADR reports received which resulted in prolonged hospitalisation and (iii) the number of reports received which resulted in prolonged hospitalisation AND had a fatal outcome?

In relation to the fatal outcomes could you please provide a table showing the ten drugs that were most frequently recorded as having caused such a reaction along with the number of times each one was recorded as having a fatal outcome.”

The MHRA continuously monitors the safety of medicines and vaccines through a variety of pharmacovigilance processes including the Yellow Card scheme. As part of our signal detection processes each fatal adverse drug reaction report received by the Yellow Card scheme is individually assessed and cumulative fatal information reviewed at regular intervals.

As with any serious suspected ADR, reports with a fatal outcome are fully evaluated by the MHRA, including an assessment of post-mortem details if available, to consider whether the medicine (or vaccine) may have caused the event, or whether the event and fatal outcome were likely to be purely coincidental and due to underlying illness. The MHRA hold weekly signal meetings in which drug/vaccine-reaction combinations which meet defined criteria are assessed by a group of scientists, physicians and pharmacists to determine if riskminimisation measures need to be implemented. This includes potentially unrecognised drug interactions. Any emerging evidence relating to possible risks associated with medicines and vaccines, would be carefully reviewed and, if appropriate, regulatory action would be taken if any serious risks were confirmed.

I can confirm that the MHRA has received a total of 40,935 UK spontaneous suspected ADR reports received between 01/01/2020 and 31/12/2020 (data extracted 09/04/2021). Table 1 below shows the number of these reports that indicate a fatal outcome as well as the number considered serious due to the selection of hospitalisation or prolonged inpatient hospitalisation from the 6 serious categories1 available.

1. Table 1 – UK spontaneous ADR reports received by the MHRA in 2020 (01/01/20– 31/12/2020 inclusive). This data was extracted on 09/04/2021.

name	Fatal	Hospitalised	Hospitalised with fatal outcome
Number of reports	1564	7270	334

As requested, please see Table 2 below of the ten most frequently reported drug substances that report a fatal outcome in the spontaneous ADR reports received in 2020.

2. Table 2 – Drug substance with the highest number of ADR reports with a fatal outcome received in 2020 (01/01/20– 31/12/2020)

Rank	Drug name	Number of ADR reports with a fatal outcome
1	CLOZAPINE	466
2	APIXABAN	31
3	RITUXIMAB	23
4	TACROLIMUS	22
5	DENOSUMAB	22
6	RIVAROXABAN	22
7	PREGABALIN	21
8	NINTEDANIB	20
9	DIAZEPAM	19
10	TOZINAMERAN	19

*Please note that the sum of reports in the table will not be equal to the total number of unique fatal reports as one report may contain more than one suspect drug.

As mentioned in our previous FOI response (FOI 20/165), Yellow Card data for clozapine is subject to reporting bias which results in an unusually high number of reports compared to other medicines. This is because people treated with clozapine in the UK are required to undergo weekly, 2-weekly or monthly blood monitoring and are monitored more closely in clinical practice than patients receiving most other medicines. This in turn increases the likelihood that adverse reactions, as well as co-incidental medical events, are detected and reported to us.

When considering the above information it is important to note that an ADR report is not proof of a side effect occurring but a suspicion by the reporter that the drug may have caused the side effect. The fact that symptoms occur after a drug is given does not mean that they are caused by the drug itself as underlying or undiagnosed illnesses and other factors may be responsible.

Furthermore, the number of reports received via the Yellow Card Scheme does not directly equate to the number of people who suffer adverse reactions to drugs for a number of reasons. ADR reporting rates may be influenced by the seriousness of reactions, their ease of recognition, extent of use of a particular drug or vaccine and promotion and publicity about a drug/vaccine.

I hope the information provided is helpful. The MHRA encourages the use of Yellow Card data however wishes to ensure that the data is studied and applied appropriately, and any conclusions/interpretations consider the above information. For this reason, if you wish to use this information for a publication, we request that you engage with the MHRA during this process and provide a copy of the report. If you are dissatisfied with the handling of your request, you have the right to ask for an internal review. Internal review requests should be submitted within two months of the date of this response; and can be addressed to this email address.

Yours sincerely,

FOI Team,

Vigilance and Risk Management of Medicines Division

1 The seriousness criteria for ADR reporting were determined by a working group of the Council for International Organizations of Medical Sciences (CIOMS) and are defined as 6 possible categories which are documented on the Yellow Card. Reporters can select one or more of the following criteria by ticking the appropriate box on the Yellow Card. The criteria are: (1) patient died due to reaction (2) life threatening (3) resulted in hospitalisation or prolonged inpatient hospitalisation (4) congenital abnormality and (5) involved persistent or significant disability or incapacity or (6) if the reaction was deemed medically significant.