Andrew Herxheimer’s Golden Rules of Using Medicines

Today is the final day of the MHRA‘s contribution to a Europe wide social media campaign from the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) programme to improve the reporting of adverse drug reactions (ADRs) to schemes like the Yellow Card Scheme. Perhaps ironic, given this is occurring in the week we hear EMEA will be moving to Amsterdam.

It reminded me that I should share Andrew Herxheimer‘s golden rules on using medicines. Andrew was a sad loss to the drug safety community in 2016. I was lucky enough to have met Andrew at several drug safety conferences over the years, and worked on the odd committee with him. The first conference I ever presented at (European Society of Pharmacovigilance Verona, 2000), I cautiously presented some work on coding of ADRs. The first comment from the audience? Andrew with “Yes, very interesting, but what are are you going to do about it.” His emphasis. That was the first time I met him.

Reporting adverse drug reactions was in his Golden Rules of prescribing, which Jeff Aronson skillfully paraphrased in the BMJ.

Andrew Herxheimer’s Golden Rules on using medicines.

  1. Think what you could do instead of using a medicine.
  2. Unless you have a special reason, avoid new medicines. Stick to those about which a lot is known from many sources and which have been used for over 10 years; bad news about a drug often takes years to emerge.
  3. Before deciding to use a medicine be clear whether it is to relieve a symptom, to cure a disease, to remedy some deficiency, or to prevent something. It doesn’t make any sense at all to prevent something in the future if it’s going to cause you some problem now.
  4. Ask a doctor or pharmacist you trust, someone who understands it a bit better than you do, how well the medicine works, what problems people have had with it, and what happened.
  5. If you have to take medicines, get to know as much as you can about those that help you.
  6. Everybody is different and you must learn how your own body reacts to medicines.
  7. Keep a diary of your experiences with a medicine: why you took it, how much for how long, what happened and when, how well it worked, and anything you didn’t like.
  8. If something bad happens that you suspect may have been caused by a medicine, report it on a yellow card; ask a doctor, pharmacist, or nurse to help you do that or to do it for you.
  9. When you have a problem about an adverse reaction or something difficult to discuss with your doctor, take someone with you to the consultation, because four ears are better than two; there are too many things to think about and an independent opinion is well worth having.

 

Drug safety lessons from deaths

In the Arms of Morpheus

The role of the coroner has evolved from its early tax-gathering history, when it was a method of collecting revenue from suicides for the government and investigating the English habit of murdering their Norman invaders, to a modern role of investigating sudden, violent and unnatural deaths for the benefit of all of society. We thought improving drug safety might be one of those benefits.

The coroner system exists in some form across the world. Since medication errors are a worldwide problem, information from deaths suspected to be due to medication reported by coroners would be a potentially useful source of pharmacovigilance data. A colleague and I, and one of our first MPharm graduates from the University of Birmingham, decided to investigate the utility of UK coroner reports concerning medication errors.

We found their reports reflected some current and longstanding drug safety concerns, with opiates and anti-coagulants figuring in nearly half of coroners’ reports we looked at. The reports contain valuable and rich pharmacovigilance data, however some of the wider lessons from individual cases may be lost.

You can read the paper at Drug Safety here.

Post Image: In the Arms of Morpheus, Sir William Ernest Reynolds-Stephens, 1894.

Information sources for adverse drug reactions

Earlier this year, I attended the PRIMM conference, where some work I have been involved with was presented (led by Prof Janet Krska’s team at The Medway School of Pharmacy). Patients were surveyed about their information sources for adverse drug reactions.

Some of the outcomes are in line with prior research, such as a significant proportion of patients finding patient information leaflets less than easy to understand. General Practitioners were the top source of information on adverse drug reactions (69%). Pharmacists were less well used than General Practitioners(28%), and were beaten by the internet (37%). This is despite only 14% of respondents trusting the internet.

So despite being viewed as easy to access (76%) and trustworthy (73%), Pharmacists are not being appropriately used to address information deficits about adverse drug reactions. This is a pity. As the healthcare professional with arguably the greatest knowledge of medicines, Pharmacists should be a key source of drug safety for patients, and be able to interpret the drug safety data in the context of the patient’s particular circumstances. Certainly, they are in an accessible position to reduce the workload of General Practitioners in this area.

O’Donovan B, Rodgers RM, Cox AR and Krska J. Patients’ use of information sources regarding side effects Pharmacoepidemiology and Drug Safety, 2017; 26:15-16 (Prescribing And Research In Medicine Management (Uk & Ireland) Annual Conference 2017, University Of Coventry London Campus, January 28th 2017: “Deprescribing – Is Less More?”)

Brexit and Pharmacovigilance

EMA

One of the areas that the UK has led on in the EU, and worldwide, is the science of pharmacovigilance and regulatory science. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) is a world class organisation in drug regulation, and has been a leader on drug safety since the thalidomide disaster in the 1960s. Since 1995, the European Medicines Agency (EMA) has regulated drug approvals centrally and has sought to harmonise drug safety and pharmacovigilance systems across the EU and across the pharmaceutical industry. EMA is a the EU equivalent of the US’s FDA. It plays a crucial role in the provision of safe medicines, and in the delivery of new medicines across the EU’s single market.

By creating a harmonised system of regulation it allows the pharmaceutical industry to market products across Europe more easily, and yet at the same time increases the safety of medicines by pooling drug safety resources, including spontaneous reports of adverse effects. Prior to this companies had to negotiate a complex system of individual member state regulatory systems.

EMA is in large part built on a MHRA model, with a knowledge base of UK experts in drug regulation and pharmacovigilance. Even the EU legislation has the clear imprint of British expertise. The UK’s black triangle is now Europe wide. EMA is based in London, employing 600 staff (mainly British). There is concern about its future if we leave the EU.

In the event of a Brexit, which could also cast uncertainty over the future of the bank authority, Europe’s equivalent of the U.S. Food and Drug Administration may have to find a new home, in a jolt to the current drug approval system.

This could slow the approvals of medicines across Europe during this transition process, including in Britain if it has to re-engineer its system.

Losing Britain could also punch a big hole in the EMA’s scientific capability, since British experts are the biggest single contributors to its drug assessment system.

EMA would most likely re-locate to another EU state, and there would be a loss of UK staff from the agency. Drug regulation in the EU and UK would be disrupted. The pharmaceutical industry damaged for a short period. In the medium to long term, it is likely the a corresponding increase in MHRA staff (presumably obtained from EMA staff unwilling to relocate) could take over work that previously EMA carried out. In the short term, a difficult transition phase would occur. Indeed, as noted in the Reuters article above one could argue that EU drug regulation would be more damaged than the UK’s: UK experts led on 27 new drug approvals, compared to 15 by German experts in 2014 – the next highest group. Even if one accepted that the MHRA would adjust relatively quickly compared to EMA, the damage to harmonisation, and pooled resources for drug safety, would be a net loss for the UK.

UK pharmaceutical companies may also end up having to apply for UK licencing and EU licencing, unless the UK was willing to accept drug licencing from an EU body they are no longer part of (which is as unlikely as them accepting FDA approvals, and hardly the ‘sovereignty’ the Leave group are voting for).

Drug regulation and pharmacovigilance may not be the deciding factor for anyone in the EU vote, but it highlights the complexities of the relationships we have in the EU. A Leave vote should come with a drug safety warning in this area at least.

Be better than the average: The Yellow Card App

For the past 50 years the Yellow Card scheme has been an essential patient safety resource. Like the UK’s blood donation scheme it depends on altruism. Reports are made by by patients, carers, and healthcare professionals of suspected adverse drug reactions (side effects) to medicines.

It saves lives. It reduces morbidity. It creates safety information for others.

Yet, the average number of reports per healthcare professional is less than 1 per year.

If you want to be better than the average healthcare professional, then download the Yellowcard app (IOS here and Android here) and take the time to report just one ADR this year.

You have benefited from Yellow Card data if you are a patient or a professional. Give something back. Report the next suspected ADR you come across.

Better still, make it a habit of your professional practice.

Yellow Card Scheme 50 today

Tuesday will see the 60th year since the breaking of the four minute mile by Roger Bannister, but today has an equally important milestone. The UK’s Yellow Card scheme for the collection of spontaneous reports of suspected harm from medicines was started 50 years ago today.

Derrick Dunlop's letter
The 1964 letter establising the Yellow Card scheme

The scheme was started after the failure to detect serious birth defects associated with the drug thalidomide (my post on the 50th anniversary since thalidomide was launched is here). Since then the scheme has been an extremely useful tool to help detect signals (a brief discussion of what a signal is here) of drug harm. During the past 50 years, there have been ups and downs, including notable problems such as practolol and benoxaprofen, but the scheme has undoubtedly led to safer drugs in the UK. It, and the pharmacovigilance expertise of the UK, has been influential worldwide, particulary in the European Union. Even in the first year of its operation, the scheme was able to issue a warning of drug safety.

Derrick Dunlop’s name is on the letter, but the man whose name is most associated with the formation of the scheme is Dr BIll Inman. Inman contracted polio at the age of 21, undertaking his medical training in a wheelchair (more on him here). In the early years of the Yellow Card scheme, Bill Inman manually examined hundreds of Yellow Cards, sorting and piling differing reports by hand, to prove that the risk of thrombosis associated with early oral contraceptives could be reduced by lowering the dose.

That’s fifty years of doctors (and now all professionals and patients) reporting to the Yellow Card scheme as a simple act of altrusim – there is no payment. Every card is of help to future users of medicines, by helping regulatory agencies keep their eye on emergent drug safety issues.

If you want to celebrate the Yellow Card scheme’s fiftieth birthday, honour it, and the memory of Dr Bill Inman, not by sending a card, but by sending a Yellow Card next time you suspect a medicine has harmed either yourself or a patient.