Appendix C: Prescribing Regulations, Policies and Guidance – Implications of the Cass Review for Scotland: report of findings

Appendix C: Prescription Regulations, Policies and Guidelines

Regulation of drugs

The regulation on drug licensing is reserved uk Government. The regulations involved are the Human Medicines Regulations 2012. Parts 3-5 cover the regulations relating to licensing. They describe the approach to authorization (licensing) of products; for the production, import, distribution, sale and supply of those products; for their labeling and advertising; and for pharmacovigilance (the detection, evaluation, understanding and prevention of adverse effects or other drug-related problems associated with pharmaceutical products).

Medicines and Health Products Regulatory Agency (MHRA) is uk drug and medical device regulator.

Before a drug can be marketed, a pharmaceutical company must be able to demonstrate its safety, quality and efficacy. This is done through a series of rigorous clinical trials, consisting of four phases.

Clinical pharmaceutical trials for drugs to meet licensing requirements

Each phase of a clinical trial varies in size, character and focus:

Phase 1 primarily determines how a drug works in humans and helps predict the dosage range for the drug and involves healthy volunteers;

Phase 2 tests efficacy as well as safety among a small group of patients (100-300) with the condition for which the drug was developed;

Phase 3 includes a much larger group (1000-5000) of these patients, who will help determine whether the drug can be considered safe and effective; AND

Phase 4 trials are conducted after a drug has been granted a license and include real-world trials to develop new treatment uses for the drug, compared with other treatments for the condition, and to determine the clinical effectiveness of the drug in a much wider variety of conditions. wide range of patient types in real-life settings. Safety is a key part of phase 4 trials, which often include several thousand patients so that rarer side effects, if any, can be detected.

Applications for MHRA for a marketing authorization must include data demonstrating the quality, safety and efficacy of the drug. Once the detailed assessment and provision of data is satisfactory, a marketing authorization (sometimes called a licence) may be granted.

A marketing authorization is granted to the manufacturer to market the medicine for a specific indication and NO to the medicine itself.

All licensed medicines must have a summary of product characteristics (SPC) and a patient information leaflet (DRINK). These contain information about what a medicine is used for, how it should be used and what risks may be associated with the medicine. of SPC is available to prescribers and DRINK it is written specifically for patients.

of MHRA strives to ensure that all known side effects of licensed medicines are documented so that patients and doctors are informed of them. However, it is not possible to predict which individuals may be at risk or when side effects may occur.

Pharmacovigilance management of the risks and benefits of drugs

Despite extensive research in clinical trials for a specific drug, some adverse drug reactions (ADRs) may not be seen until a very large number of people have taken the drug. It is therefore vital that the safety of all medicines is monitored throughout their market life – this is known as pharmacovigilance.

Pharmacovigilance involves monitoring the use of drugs in daily practice to identify previously unrecognized side effects or changes in side effect patterns, evaluating the risks and benefits of drugs to determine what action, if any, is needed to improve their safe use by providing information. healthcare professionals and patients to optimize the safe and effective use of medicines and monitor the impact of any action taken.

For a drug to be considered safe, its expected benefits must outweigh any associated risk of adverse reactions. All drugs can cause reactions; however, most people take the medication without experiencing any serious side effects. Health care professionals should be able to discuss such information with patients, parents and caregivers, be vigilant in detecting suspects. ADRs and to encourage their reporting through a MHRA the process called the Yellow Card Scheme.

Information from many sources is used for pharmacovigilance. These include spontaneous adverse drug reactions (ADR) reporting schemes, for example, the yellow card scheme; clinical and epidemiological studies; medical literature published worldwide; pharmaceutical companies; regulatory authorities worldwide; and morbidity and mortality databases.

Description of drugs

The decision to prescribe a drug for a person and which drug to prescribe is entirely up to the clinician caring for them, taking into account the person's clinical condition and any relevant clinical guidelines.

As part of the medical responsibility of doctors, their primary necessity under the General Medical Council (GMC) regulation and accountability must first do no harm; in other words, a doctor is accountable for the care he provides, or fails to provide, to the person he treats, to the regulator and to his employers through the channels of clinical governance and not to any other party.

Clinicians must usually prescribe licensed drugs in accordance with the terms of their marketing authorisation. However, they may prescribe unlicensed or off-label drugs uk marketing authorization) where, based on an assessment of an individual person, they conclude, for medical reasons, that it is necessary to do so to meet that person's specific needs.

Prescribing unlicensed or off-label medicines may be necessary if, for example, there is not an appropriately licensed medicine to meet the person's needs (this is often the case with children where a medicine is only licensed for adult), a licensed medicine is not available due to a temporary shortage in supply, or the prescription is part of research. From time to time, clinicians may prescribe a drug when the product license does not cover the indication if they feel there would be significant clinical benefit to the patient and in accordance with local Health Board governance processes and protocols.

A clinician is professionally and clinically responsible for any medication they prescribe. The liability that falls on them, and on the dispenser of that drug, when they prescribe an off-label drug or an unlicensed product is greater than when they prescribe a licensed drug within their license.

of GMC The Guidelines for Good Practice in the Prescribing and Management of Medicines and Devices advise that clinicians, when prescribing in the following circumstances: are satisfied that there is sufficient evidence or experience of the use of the medicine to demonstrate its safety and efficacy; take responsibility for prescribing the medicine and for supervising the care, monitoring and any follow-up treatment of persons, or ensuring that arrangements are made for another suitable doctor to do so; and make a clear, accurate and legible record of the reasons for prescribing an unlicensed/off-label drug.

Clinicians should provide patients, or their parents or guardians, with sufficient information about the medicines they propose to prescribe to allow them to make an informed decision. It is more difficult to obtain pharmacovigilance data when drugs are prescribed off-label.

Off Label Description of Puberty Suppressors Hormones

There are no drugs licensed to suppress the onset of puberty.

National Institute for Health and Care Excellence (GOOD) completed a review of the evidence on this topic in 2020, which included nine observational studies. The quality of evidence for the critical outcomes identified for decision-making, gender dysphoria and mental health was assessed at the time as very low certainty. There was no statistically significant difference in the measurement compared to baseline. No evidence was found for quality of life. The quality of the evidence reported for important outcomes was also rated as very low certainty.

A restart of the search was undertaken by NHS England (NHSE) in April 2023 to capture the literature published after GOOD Review of evidence in 2020. A further nine studies were identified.

Subsequent evidence in other contexts has shown that the use of puberty-suppressing hormones may be associated with significant harm in some as well as benefit in others. Growing evidence suggests that these drugs are certainly not harmless and are not as safe to use as first thought.

Furthermore, this evidence base does not provide adequate data to address questions about long-term benefits or harms regarding mental health, bone health, fertility, or other as yet unknown risks at a very critical stage in growth and child development.

NHSE concluded in March 2024 that there was insufficient evidence to support the safety or clinical effectiveness of puberty-blocking drugs to make the treatment routinely available at present.

Clinical Perspectives Off-label description of puberty-suppressing hormones

Based on the most recent evidence, clinicians who are specialists in this field have established a consensus that it is no longer safe to continue recommending these drugs without further evidence developed within the rigorous clinical trials that apply to all drugs of others. It is their concern about the well-being and health of the children in their care that has led doctors to this decision.

In April 2024 NHS Greater Glasgow and the Clyde (GGC) and NHS Lothian issued a joint statement stressing that both Health Boards would ban any new prescribing of GnRH analogues through their Pediatric Endocrinology teams for children and youth under 18 with the goal of puberty suppression. Existing children and young people taking these drugs were not affected by the pause. An exercise was undertaken to ensure that all children and young people directly affected by this change were notified before the announcement.