How MHRA monitors the impact of regulatory action taken.
Article date: August 2009
MHRA is very aware of the need to monitor the impact of the actions we take on medicines, whether these result in a widening or restriction of access. It is important for us to ensure that our decisions have a positive outcome for users of medicines.
Our commitment to this important area of research is outlined in our current business plan.This article outlines how we try to ensure we optimally safeguard public health by: conducting our own research; working collaboratively with academic groups and other agencies; commissioning research; and requesting specific research from the pharmaceutical industry (marketing authorisation holders) where appropriate.
We perform studies to provide better information on the pattern of usage of medicines to inform decisions we are about to make; or to examine the impact of regulatory action that has been taken. For example, we might need to identify patterns of use for established medicines before reclassification of a product from prescription-only to pharmacy supply; to examine patterns of use after regulatory action; or assess usage of other medicines in the event of a drug withdrawal.
We also carry out studies to investigate potential new safety issues using databases such as the General Practice Research Database.
Commissioned research programme
In April 2005, we announced a call for research proposals to study the safety of medicines. As a result, the following studies were commissioned:
- The safety of antiepileptic drugs in children (London School of Pharmacy)
This study specifically looked at the safety of newer antiepileptics compared with the more-established drugs in children, and did not identify any specific safety concerns. This study was presented at the European Society for Developmental Perinatal and Paediatric Pharmacology, Rotterdam 2008, and the International Conference of Pharmacoepidemiology, Copenhagen 2008.
- The impact of regulatory action taken by the MHRA on COX-2 inhibitors1 and SSRIs 2 3(University of Bristol)
The COX-2 study aimed to investigate the effects of withdrawal and regulatory advice for COX-2 inhibitors on UK rates of gastrointestinal haemorrhage and acute myocardial infarction. It found that such action did not appear to have any adverse effect on population health and may have been beneficial.
The SSRI studies analysed whether the restriction of the use of SSRIs in children and adolescents had lead to an increased risk of suicide in these age-groups, and found that there was no evidence that this had occurred.
- The use of the General Practice Research Database to provide earlier information on the safety of drug use in children before conducting a trial (Queen Mary and Westfields College London, study ongoing)
It is hoped that a preliminary study using this database could help researchers plan their trial specifically for the target population.
We also work collaboratively with external academic groups or other government agencies (such as the Health Protection Agency) to carry out studies of mutual interest. Examples of such collaborations include:
- University of Bristol—risk of suicidal behaviour related to antidepressants4 and smoking-cessation therapies (submitted for publication)
This antidepressant study4 found no evidence that the risk of suicide or non-fatal self-harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants. Weak evidence was found for an increased risk for current SSRI use in those age 18 years or younger. However, a bias of preferential SSRI prescribing to patients at higher risk of suicidal behaviour cannot be ruled out.
- Health Protection Agency—risks of Guillain-Barré syndrome and Bell’s palsy after influenza vaccination5 6
These studies found no evidence of increased risk.
University of Oxford, Cancer Research UK Epidemiology Unit—GP prescribing trends in HRT, tibolone, and bisphosphonates between 1991 and 2005 for prevention and treatment of osteoporosis in relation to published research on health effects of these medicines and changes to prescribing advice7
The study found that prescribing of HRT had fallen by about 50% since 2002, which reflected new epidemiological evidence and prescribing advice. Bisphosphonate prescribing increased during the study period, partly reflecting the availability of weekly formulations.
External research groups
In addition to specific collaborative studies, the MHRA has good links with various academic research groups and monitors the published literature, for research relevant to regulatory action that we may have taken. One example of this is the recent work published by K Hawton and colleagues8 on the effect of the phased withdrawal of coproxamol on deaths from drug poisoning.
Research by the pharmaceutical industry
A marketing authorisation holder for a medicine is required to agree at the time of licensing what research they intend to conduct to gather further information on the safety of their products. Although post-authorisation studies have been conducted for many years,9 the legal requirement for risk management plans is more recent.
A risk management plan provides an overview of the known safety profile of the product by summarising the data from clinical trials and other studies. Any important identified risks are also discussed, along with the proposals for minimising these risks and for further studies to investigate the safety of the product once it is in routine use. Generally, marketing authorisation holders are responsible for carrying out these studies, but the methodology is discussed and agreed with the regulatory authority.
For an example summary of a risk management plan for the smoking-cessation treatment varenicline and further information on risk management plans, see Guideline on Risk Management Systems for Medicinal Products for Human Use on the European Medicines Agency (EMA) website.
Article citation: Drug Safety Update Aug 2009, vol 3 issue 1: 7.
Wheeler B, et al. Br J Clin Pharmacol accepted article July 6 2009; doi 10.1111/1365-2125.2009.03500.x. (accessed July 22, 2009). ↩
Wheeler B, et al. Pharmacoepidemiol Drug Saf 2009; 18: 579–88. ↩
Wheeler B, et al. BMJ 2008; 336: 542–45. ↩
Martinez C, et al. BMJ 2005; 330: 373–74. ↩
Stowe J, et al. Am J Epidemiol 2009; 169: 382–88. ↩
Stowe J, et al. Hum Vaccin 2006; 2: 110–12. ↩
Watson J, et al. Eur J Clin Pharmacol 2007; 63: 843–49. ↩
Hawton K et al. BMJ 2009; 338: b2270. ↩
Waller P, et al. BMJ 1992; 304: 1470–72. ↩