FOI release

Freedom of Information request on the adverse reactions reported regarding beclomethasone, betamethasone, clobetasol, hydrocortisone and mometasone (FOI 22/752)

Published 21 December 2023

FOI 22/752

5th July 2022

Dear

Thank you of your email dated 07 June 2022, where you requested data regarding beclomethasone, betamethasone, clobetasol, hydrocortisone and mometasone and for some guidance on using and interpreting data in the interactive Drug Analysis Profiles (iDAPs).

Each iDAP contains complete data for all spontaneous side effects, known as suspected adverse drug reactions via the Yellow Card scheme received directly from healthcare professionals (HCPs), and members of the public as well as indirect reports from industry who are legally obliged to report to us. For accurate data to be provided with regards to reporter qualification, only direct reports will be included in this data. Therefore, any reports from pharmaceutical companies have been removed.

When considering the below provided spontaneous Adverse Drug Reaction (ADR) data, it is important to be aware of the following points:

• A reported reaction does not necessarily mean it has been caused by the drug, only that the reporter had a suspicion it may have. The fact that symptoms occur after use of a drug, and are reported via the Yellow Card scheme, does not in itself mean that they are proven to have been caused by the drug. Underlying or concurrent illnesses may be responsible and such events can also be coincidental.

• It is also important to note that the number of reports received via the Yellow Card scheme does not directly equate to the number of people who suffer adverse reactions and therefore cannot be used to determine the incidence of a reaction. ADR reporting rates are influenced by the seriousness of ADRs, their ease of recognition, the extent of use of a particular drug, and may be stimulated by promotion and publicity about a drug. Reporting tends to be highest for newly introduced medicines during the first one to two years on the market and then falls over time. For these reasons the enclosed data should not be used as a basis for determining incidence of side effects.

Further to your request, I am pleased to provide you with Table 1 showing the total number of UK, direct, spontaneous suspected ADR reports for each medicine up to and including 26/06/2022. Please also see Tables 2, 3 and 4 which show a breakdown of reporter qualification for each requested medicine which contains information on all UK, direct, spontaneous suspected ADR reports received through the Yellow Card scheme for that medicine in 1969 (Table 2), 1989 (Table

3) and between and including 2002 - 27/06/2022 (Table 4). To note, the MHRA uses standard qualifications set by The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Unfortunately, the set does not include the granular detail of dermatologist and so, any dermatologists reporting will fall within one of the available groups depending on where they are based and what they selected when reporting. In addition, the data we have on reporter qualification from 1969 and 1989 is less detailed than more recent years as the options for selection have increased over time. Finally, where less than 5 reports have been received for a specific medication and qualification, an asterisk has been used to conceal this number in order to comply with data protection laws and protect patient/reporter confidentiality.

Table 1. All direct UK spontaneous suspected Adverse Reaction reports for hydrocortisone, beclomethasone, clobetasol, mometasone and betamethasone separated by healthcare professional and patient/carer.

Hydrocortisone		Beclomethasone		Clobetasol		Mometasone		Betamethasone
HCP	Patient/ Carer	HCP	Patient/ Carer	HCP	Patient/ Carer	HCP	Patient/ Carer	HCP	Patient/ Carer
727	296	2300	592	66	78	174	196	318	274

Table 2. Direct UK spontaneous suspected Adverse Reaction reports received in 1969 for hydrocortisone, beclomethasone, clobetasol, mometasone and betamethasone separated by reporter qualification.

	Hydrocortisone	Beclomethasone	Clobetasol	Mometasone	Betamethasone
Other Healthcare Professionals	9				5
GP					*

Table 3. Direct UK spontaneous suspected Adverse Reaction reports received in 1989 for hydrocortisone, beclomethasone, clobetasol, mometasone and betamethasone separated by reporter qualification.

	Hydrocortisone	Beclomethasone	Clobetasol	Mometasone	Betamethasone
Other Healthcare Professionals	33	63	*		*

Table 4. Direct UK spontaneous suspected Adverse Reaction reports received from 2002 up to and including 27/06/2022 for hydrocortisone, beclomethasone, clobetasol, mometasone and betamethasone separated by reporter qualification.

	Beclomethasone	Betamethason	Clobetasol	Hydrocortisone	Mometasone
Community Pharmacist	186	16		17	18
Dentist	*	*	*		*
GP	384	62	8	46	42
Hospital Doctor	33	56	*	27	13
Hospital Healthcare Professional	*			13	*
Hospital Nurse	27	*	*	20	*
Hospital Pharmacist	43	12	*	40	*
Medical Student		*
Midwife		*
Nurse	497	16	*	25	12
Optometrist	*	*		*
Other Healthcare Professionals	57	12	*	15	5
Paramedic	*			*
Pharmacist	113	6	*	15	*
Pharmacy Assistant	15	*	*	*	*
Physician	11	*		*	*
Pre-rep Pharmacist	15	*	*	*	*

In response to your additional questions, please see below responses:

1.I am particularly interested in how to draw out data on the Interactive Drug Analysis Profile, a link to which you kindly provided. In the Interactive Drug Analysis Profile: could you confirm in the ‘Route of administration’ search, after identifying a drug for example Betamethasone, I would need to tick both CUTANEOUS USE and TOPICAL boxes as my particular interest was skin disorders? If not could you advise?

Where applicable the route of administration can be used to filter the reports to the subset you require, in this case topical and cutaneous use. To note however, route of administration is not a mandatory field and as such will not always be provided by the reporter.

2.I am puzzled as to exactly how detailed clinical adverse reaction data i.e. section ’Selected reactions by organ class, higher level group term etc…….’ is identified from Yellow Card submissions, many of which have been submitted by patients or carers?

It may be helpful to provide some information on the dictionary that we use when classifying ADR reports. MedDRA (Medical Dictionary for Regulatory Activities) is a clinically validated international medical terminology dictionary. It’s organised by System Organ Class (SOC), divided into High-Level Group Terms (HLGT), High-Level Terms (HLT), Preferred Terms (PT) and finally into Lowest Level Terms (LLT). We use this to code our ADR reports within our database. When patients and health care professionals are completing electronic Yellow Card reports they are able to type in the side effect which will populate a drop-down list containing suggested MedDRA LLT terms based on what they have entered. If the reporter cannot find a term which fits, then they can fill in this field with free text and one of our trained signal assessors will select an appropriate term or terms when evaluating the report. Similarly, if the reporter mentions an additional ADR in the report outside of the side effects section, then our assessor would add this too. If our assessors are unsure on any ADR being reported, where possible, they follow up with the reporter to clarify this.

I hope the information provided is helpful, but 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