Legalize acetylcysteine: An open letter to the UK's MHRA
========================================================

Executive summary: Acetylcysteine is a common medicine used in Spain without prescription that I believe is a better alternative than the medications used in the UK to relieve some symptoms of the flu. There is a legal framework for importing it from Europe, but it onerous enough that I'm not going to personally do it, so the idea is there for the taking. A few companies have bothered to go through the process already, so it might make sense to partner with them. It might also be valuable to streamline the process of importing medicines into the UK from the EU, but this seems harder.

## Part I: Demagoguery

This is the map of maximum Celtic expansion, in circa 270 BC, per [Wikipedia](https://upload.wikimedia.org/wikipedia/commons/0/08/Celtic_expansion_in_Europe.svg):

![](https://upload.wikimedia.org/wikipedia/commons/0/08/Celtic_expansion_in_Europe.svg)

Since then, the Spaniards have further developed into Gazpacho-drinking siesta-sleepers and the Britons have developed into tea-drinking weather-contemplators[^1]. Still, my understanding is that population differences are to a great degree cultural, and that the basic plumbing remains pretty much the same[^2].

Imagine, then, my surprise, when in the middle of being sick in the UK, I find out that an extremely common medicine used to treat the cold in Spain throughout my childhood just wasn't commonly available in the UK. This medicine is [acetylcysteine](https://en.wikipedia.org/wiki/Acetylcysteine)—known in Spain under the brand name "Fluimicil"[^3]. It's purpose is to decrease the thickness of the mucus so that it can be expelled, so that the patient can better breathe. In my experience, this is particularly crucial at night, because if the nose is blocked, you will breathe through the mouth and end up having a sore throat, and generally not sleep as well. 

Instead of using acetylcysteine, the UK uses other less efficaceous medicaments, such as nose sprays, which don't work as well through the night. They aren't as useful once the nose is already blocked. And they are more annoying to use, which means that people may forget them completely—or just use them less. Brits also have access to [Carbocysteine](https://www.nhs.uk/medicines/carbocisteine/#:~:text=A%20mucolytic%20helps%20you%20cough,chronic%20obstructive%20pulmonary%20disease%20), though only with a prescription, and in practice it doesn't seem to be standard of care.

## Part II: Cost-effectiveness analysis

I work as a forecaster, not as a doctor or as a medical researcher. So there are surely factors I'm missing. For instance, maybe living for two milenia under lousy weather has maybe made the population of Britain more immune to having blocked noses, and this could mean that nose sprays are a better tradeoff than acetylcysteine. I really wouldn't know, though it would surprise me. 	

Still, as a forecaster I can offer the following estimation:

Per the [NHS inform website](https://www.nhsinform.scot/illnesses-and-conditions/infections-and-poisoning/common-cold#colds-in-children): 

> Children get colds far more often than adults. While adults usually have two to four colds a year, children can catch as many as 8 to 12.

According to the [latest data from the Office of National Statistics](https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/timeseries/ukpop/pop), the population pyramid of the UK looks as follows:

![](./population.png)

meaning that there are 67,081,234 people, of which 20.1% (13,468,262) is under 16. I also estimate that acetylcysteine makes an illness somewhere between 1% and 10% better. 

Putting this together, I can [estimate the following](https://www.squiggle-language.com/playground#code=eNqFkV9rwjAUxb%2FKpbChnfPfnAPBR5%2FGXiZ7C4TYxBpIb7r0dlLE775E7aa1c2%2Fl9OR3TnJ2UbGx22WZZcJV0YxcqXoHaSE1WVcrGjVpYZafpU5To5bkNKbRLGI4GMCiIJ0JUrAqnVQIdg1SF0oUimFu89II0ha5XfOPV5jD9OXN687m1h30ZKONdP7cHIb98XAEHjke9kd3DMmSMFzI0hBPrJEFz5XjlRLOmztjIAuTLsRwlRJDZwSP0JLSram10AKeBPBo%2FAe5BfrDDChPuNH7AW7GM5Sl%2B8kL%2F8KLHfuEh5GiKuq08M23mja177xEDE3QeclD1m%2FTBmkAT9Nnhpfj6iwXCYVxRaKoMklVkNKowGLb8N7u7JfKFNKR3DgVxvZb%2B4v5qRmmQmPByfKV4htxeZlT2Rj%2BYZ4avysqHcJ96JIbUTHcMYQr3uxK6QVbo8isKXjTnmG0%2FwYbRy4m):

```
// Estimate burden of disease
population_of_UK = 67M
proportion_children = 0.201 // 20.1%
total_adult_colds_per_year = (2 to 4) * population_of_UK * (1 - proportion_children)
total_children_colds_per_year = (4 to 12) * population_of_UK * proportion_children
total_colds = total_adult_colds_per_year + total_children_colds_per_year
duration_of_cold = 6 to 12 // days
total_days_with_cold = total_colds * duration_of_cold
total_cold_years = total_days_with_cold / 365

// Estimate impact of acetylcysteine on burden of disease
improvement_with_acetylcysteine = 0.01 to 0.1
gains_to_be_had = total_cold_years * improvement_with_acetylcysteine

// Return & display
{
  total_cold_years: total_cold_years,
  gains_to_be_had: gains_to_be_had,
}
```

That is, I arrive at an estimate of 6M (1.7M to 9.2M) cummulative person-years per year spent having a cold in Britain:

![](./cold_years_per_year.png)

and a potential improvement from adopting acetylcysteine of 250,000 (53,000 to 640,000) "quality-adjusted-sickness-years"—an intutitive, ad-hoc unit that I just made up:

![](./gains-to-be-had.png)

The weakness of the method is that my subjective estimates of the 1% to 10% quality of life improvement might be off, or that my estimates of how often people are sick might be inaccurate—6M years of cold per year does seem a bit high. I'm also not really familiar with how potential alternatives, such as carbocisteine, are used in the UK. Still, I think that this rough calculation does show that having better medicaments is of great importance. And the Spanish doctors I've spoken expressed shock and disbelief that acetylcysteine was not available in the UK.

One particular way my estimate could be wrong is if patients are taking carbocysteine instead of acetylcysteine, and if the two medicaments closely resemble each other. If that is the case, the above estimates might be much lower. Still,, they still point to the broader correct point that really nailing standard of care for the flu is likely to be very valuable.

But while an abstract argument may have been made, the action and followup remains. And it falls on the brave and hardworking souls at the [MHRA](https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency) to send [a Message to Garcia](https://courses.csail.mit.edu/6.803/pdf/hubbard1899.pdf): Legalize acetylcysteine. 

## Part III: The invisible hand defeated

But in fact, acetylcysteine is already legal in the UK. Well, pseudo-legal. Quasi-legal. Legal in name, but not legal enough for the invisible hand of the market to do its work.

By this I mean that you could in theory sell acetylcysteine if you have a number of licenses which look very annoying to get. Per the MHRA's website:

> If you want to parallel import a product you must make sure that:
> - the product is manufactured to [good manufacturing practice (GMP) standards](https://www.gov.uk/guidance/good-manufacturing-practice-and-good-distribution-practice)
> - you hold a [wholesale dealer’s licence](https://www.gov.uk/guidance/apply-for-manufacturer-or-wholesaler-of-medicines-licences) covering importing, storage and sale for each product
> - you hold the correct parallel import licence
> 
> To assemble and repackage the product you will also need to have an [manufacturer’s licence](https://www.gov.uk/guidance/apply-for-manufacturer-or-wholesaler-of-medicines-licences) covering product assembly.

You know what this prevents me from doing? This prevents me from buying 1 000 packages of acetylcysteine and selling them to friends on the side, and then relying on word of mouth. I would have been the invisible hand of the market, if only I hadn't been stymied by government regulations.

In fact, regulations aren't so bad. It seems conceivable that I could figure these requirements out during a summer. Though I'm probably not going to, so this idea is free for the taking. In practice, there are already [a few companies](https://products.mhra.gov.uk/search/?search=acetylcysteine&page=1&ter=UK&rerouteType=0) that have gone through the trouble, like [Waymade](https://www.waymade.co.uk/), and so it might make more sense to partner with them.

And yet, the situation remains suboptimal. Ideally, the regulatory framework of the UK would be such that importing medicines from the EU would be painless. But that would be a much larger project. 

[^1]: As in, "Isn't the weather nice today, darling?"

[^2]: My understanding is that in general there are *some* differences in the efficacy of medical treatments across ethnic group. I previously knew that [lactose intolerance](https://en.wikipedia.org/wiki/Lactose_intolerance#Frequency) is more common across people of East Asian descent. And some brief Googling leads me to a few papers on the topic ([1](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2594139/), [2](https://www.degruyter.com/document/doi/10.1515/DMDI.1995.12.2.77/html), [3](https://www.tandfonline.com/doi/abs/10.1517/17425255.2011.585969). So it's conceivable that that consideration is part of what is going on. But it would surprise me. 

[^3] Also Normofludil, etc.