The introduction of a limit on the number of tablets sold in packets of paracetamol has led to a 43% reduction in the number of poisoning deaths, The Independent has accurately reported. This is one of those relatively rare truly "good news" health stories.

This figure is taken from a useful and reliable piece of research that looked at the long-term impact of restricting the number of tablets in paracetamol packs.

The size of paracetamol packs available over the counter has been limited by law since 1998. This research looked at the number of paracetamol-related deaths and paracetamol-related liver transplants before and after the legislation (1993 to 2009).

Researchers found an overall 43% reduction in the number of paracetamol-related deaths. There was also a 61% reduction in the number of people needing a liver transplant as a result of a paracetamol overdose. Both figures are taken from reliable national data and are statistically significant even when the general decline in the number of suicides is taken into account.

These results suggest that the law has been successful. However, the nature of this study means that it is difficult to conclude that it was the new law that was directly responsible for this decline.

As the researchers conclude, a large number of deaths due to paracetamol overdose occur every year, and further measures are needed to prevent these potentially avoidable deaths.

Where did the story come from?

The study was carried out by researchers from the University of Oxford Centre for Suicide Research and other institutions in the UK and was funded by the National Institute for Health Research. It was published in the peer-reviewed British Medical Journal.

The media report the findings of this research accurately.

What kind of research was this?

In September 1998 the UK government (on advice from the medicines safety watchdog) brought in legislation to restrict the packet size of paracetamol sold over the counter. Packets sold in pharmacies can now contain a maximum of 32 tablets and those sold outside pharmacies can contain no more than 16 tablets.

The law was introduced because of the large number of people taking paracetamol overdoses in suicide attempts, resulting in large numbers of deaths and people needing liver transplants. When paracetamol is broken down by the liver a small amount of a toxic chemical is produced. At normal paracetamol doses the liver is able to break down this chemical. At overdose levels, however, much more of this toxin is produced than the liver is able to break down and the excess toxin causes damage to the liver.

The aim of this observational study was to examine how paracetamol poisoning deaths and demand for liver transplants have changed over time from the early and mid 1990s (prior to the new law) up to 2009 after the legislation was introduced.

This is a valuable study type for examining trends over time, and collecting this sort of data is the only real way to assess the impact of legislation after it has been implemented nationwide.

As with all studies of this type it is difficult to say whether the introduction of the law is the only factor directly responsible for the changes seen as other factors could also be involved (suicide rates in general have been falling since 2000).

The study is able to indicate whether the trends seen are consistent with the law having an effect.

What did the research involve?

The researchers used data from the Office for National Statistics to look at the number of deaths in England and Wales between 1993 and 2009 that were due to paracetamol poisoning.

This number could include suicides, open verdicts (when it was unclear whether the poisoning was deliberate or accidental) and accidental poisonings. The researchers looked at deaths in people aged 10 years or over. They looked at deaths due to paracetamol alone, or deaths due to single products that contained paracetamol in combination with other medications (such as paracetamol in combination with codeine dihydrocodeine, ibuprofen or aspirin). They looked at whether alcohol was used in combination with paracetamol by those committing suicide.

As another source of information, the researchers looked at all registrations made at all liver transplant units (people being put on the transplant list) in the UK between 1995 and 2000 for liver transplant as a result of paracetamol poisoning. They restricted their analyses to people aged 10 years or over and resident in England or Wales.

The researchers used statistical methods to look at changes in trends over time. Mortality information from the Office for National Statistics and for the transplant units is provided in three-month periods (quarters). The researchers had mortality data for 23 quarters prior to the introduction of legislation and 45 quarters after introduction. They had transplant data for 15 quarters before the new law and 45 after.

The researchers also took into account general trends in non-paracetamol self-poisonings and suicides in England and Wales over this time period. They did this to test whether any changes were just part of general trends or were specific to paracetamol poisoning. The latter would support that it was the legislation having an effect rather than other more general factors.

What were the basic results?

The researchers observed a significant decrease since the 1998 legislation in the number of paracetamol-related deaths in England and Wales that received a suicide or open verdict.

There were 17 fewer deaths per quarter after the legislation was introduced than were expected, taking into account the trends observed between 1993 and September 1998 (39 per quarter pre-legislation compared with 22 per quarter post-legislation).

Overall, this means a 43.6% reduction in the number of deaths caused by paracetamol in the 11 years after introduction of legislation, or 765 fewer deaths than would have been expected based on the prior trends.

The trends remained significant even when the researchers adjusted their analysis for a general fall in the number of non-paracetamol poisonings and suicides.

Similarly, there has also been a decrease in the number of registrations for paracetamol-related liver transplant since 1998. There have been an estimated 11 fewer registrations per quarter since the law came in, compared with the expected number based on pre-law trends (18 per quarter pre-law compared with seven per quarter post-law). Overall, this equated to a 61.1% reduction in the number of registrations, or 482 fewer registrations over the 11 years post-legislation. However, the reduction in the number of paracetamol-related liver transplant registrations did not equate to a reduction in the actual number of paracetamol-related liver transplants carried out. The researchers were not sure why this was the case.

How did the researchers interpret the results?

The researchers conclude that, in the 11 years following the introduction of the 1998 law to reduce the pack sizes of paracetamol available over the counter, there has been a significant reduction in the number of deaths due to paracetamol overdose, and in the number of paracetamol-related registrations for transplantation at liver units.

However, they conclude on the sobering note that, despite the reductions, “the continuing toll of deaths suggests that further preventive measures should be sought”.

Conclusion

This valuable research suggests that the introduction of the 1998 law to limit the number of paracetamol tablets sold per pack has reduced the number of deaths and the need for liver transplants due to paracetamol overdose.

This is said to be one of the first studies to examine the long-term effects of this law and it benefits from using reliable data obtained from national registries.

A before–after observational study such as this is the only real way of collecting information about the effects of a national law after it has been introduced.

As with all studies of this type it is difficult to prove that the law was the single factor directly responsible for the changes seen. For example, if there has been a general national trend towards a reduction in suicide attempts, or a trend towards using alternative methods to poisoning, then this may also account for the changes seen.

However, when the researchers adjusted their results for a general trend towards a fall in suicide rates and a fall in the number of non-paracetamol poisonings overall, the paracetamol-related trends were still significant. This suggests that the paracetamol legislation is having this specific effect.

It is still possible that other factors may also be involved in the reduction in the numbers of paracetamol-related deaths and transplant registrations, such as improved medical treatment of paracetamol overdose, or increasing awareness about the risks of paracetamol overdose.

Despite these possible limitations, it does seem likely that the legislation is having an effect.

As the researchers rightly conclude, there are still a large number of deaths due to paracetamol overdose occurring every year (around 150–200 on average in England and Wales), and further preventive measures are needed.

Analysis by Bazian

Edited by NHS Website