How do I read the package insert in the right way?

Package inserts contain a lot of important information. But not all of them are easy to understand - and some are missing altogether. In this way, the texts arouse hopes and fears in most people. This alone can have an impact on therapy.

In clinical practice, negative expectation effects are very often triggered by reading the package insert, which is usually difficult for laypersons to understand.

Any medication that you receive - usually from your pharmacist - comes with a so-called package insert. This also includes over-the-counter medications that you can purchase without a prescription. The package insert is a small, long, folded piece of paper, mostly with very small writing, which contains important information and directions for using the medication. As a patient, you are encouraged to read all of this information carefully, but it is very important that you do not let it unsettle or confuse you! It is up to you to decide which practical details you absolutely need to know and how you should personally evaluate the information.

Package inserts do not describe the positive and desired effects of medications. There are three especially surprising and important points to keep in mind:

1. The positive information is not provided.
   You won’t find any clear information about what percentage of people who take the medication can expect to see some improvement in their symptoms. You also won’t find any detailed explanations about the mechanisms that bring about the desired effect. And you won’t find any direct indications about when you should expect to find some relief from your symptoms. But there are many positive benefits from taking a prescribed medication, such as an improvement in your symptoms and preventing the need for much more far-reaching measures later on, e.g. an improvement of depression by taking antidepressants, improved overall well-being by taking fever-reducing drugs when you have the flu, a greatly reduced risk of cardiovascular disease if you take blood pressure tablets, or pain relief when you have a headache.
   
2. The side effects listed in the package insert are not necessarily related to the medication itself.
   If the package insert lists "adverse side effects" that are "very common", this does not mean that they are actually related to the drug. Sounds confusing? Prof. Winfried Rief from the University Hospital in Marburg agrees, which is why we want to explain it in more detail here. Legislators have stipulated that all side effects which were observed, for example, in clinical trials (see Glossary) must be listed, even if it has not been verified whether these side effects were actually due to the drug in question. Please also read the text: "What are adverse effects?" All potential side effects of medications (e.g., nausea, headache, or skin reactions) must be mentioned in the drug's package insert according to the strict legal regulations governing medications. That's all well and good, and it does support patient safety, but unfortunately, the language used in package inserts to describe frequencies of side effects is often misleading or confusing if you’re not well versed in mathematical probabilities. In everyday language, we intuitively interpret percentage probabilities differently, so explanations are crucial here.
   
3. Common doesn’t actually mean common.
   How can patients better understand what the probabilities listed in the package insert really mean? When you read this information, it’s important to be aware that a side effect listed as “very common” means that nine out of ten people tolerate the drug well, i.e. the vast majority of those who take it. This is really important, because not only positive expectations, but also negative expectations, can influence your treatment. Clinically, this nocebo effect is highly significant, which is why package inserts are particularly interesting in the field of placebo research, which examines such expectation effects.

The information about the likelihood of an adverse effect is specified by law as follows:
- Very common means: more than 10%, i.e. more than one in ten people.
- Common means: 1 to 10%, i.e. 1 in 100 to 1 in 10 people.
- Uncommon means: 0.1 to 1%, i.e. 1 in 1000 to 1 in 100 people.
- Rare means: 0.01 to 0.1%, i.e. 1 in 10,000 to 1 in 1000 people.
- Very rare means: less than 0.01%, i.e. less than 1 in 10,000 people.

If your expectations are negative, this is known as a nocebo effect (Latin: "I will harm"). If, for example, you learn that someone you know didn’t tolerate a certain medication well, it’s more likely that the same medication will also have a less than optimal effect on you or that it will cause side effects. Studies have indicated that the nocebo effect (see here for more explanation) triggers processes in the central nervous system that can lead to physical changes. Fear of pain, for example, can block endogenous pain-inhibiting substances in the nervous system, so that pain conduction and perception are enhanced. Such nocebo effects probably play an even greater role in everyday life than the placebo effect, but there is much less research on them.

"In clinical practice, nocebo effects are very often triggered by reading the package insert, which is usually difficult for laypeople to understand," warns Prof. Ulrike Bingel, Director of the Interdisciplinary Centre for Pain Medicine at the University Hospital Essen and placebo researcher. The statistical information on possible side effects can unsettle patients. Even people who are good with numbers can quickly become overwhelmed when it comes to putting probabilities into context, especially since anyone taking a new medication already finds themselves in an anxiety-inducing situation.

So what does "very common" mean when it’s used to describe possible adverse side effects? This standard wording means more than one in ten people. This is described as "very common," "but this is a completely unfamiliar use of language for us," explains Prof. Bingel. Who would say that a soccer striker scores very frequently if he misses nine out of ten shots?

Prof. Ulrike Bingel often explains it to her patients like this: "Imagine that a bar of chocolate came with a package insert. The list of possible adverse effects would be very long. For instance, you could slip on melted chocolate and break your neck, choke on a piece that's too big, or go into fatal shock with respiratory distress if you have an undetected peanut allergy." Of course, these things are very unlikely to happen, as are many of the possible side effects listed in package inserts for medications. If you consume one bar of chocolate, or maybe even half a bar, there is already a greater chance that you will suffer from bloating afterwards, or become tired and unfocused. If you frequently (!) polish off a whole bar, it’s quite possible that you will develop obesity and diabetes, a resulting lack of physical activity, and a heart attack or stroke. And let’s not forget the tooth decay if you don’t brush your teeth afterwards. Despite this, millions of people enjoy eating chocolate because they like the taste, and in moderation it does them good.

With this true-to-life and deliberately humorous example, our aim is not to minimize the possible risks of drug treatment. Rather, we want to help patients to more consciously weigh up the benefits and harms of treatments and to be better able to absorb the necessary information without fear”, explains Prof. Winfried Rief from the University Hospital in Marburg and Prof. Ulrike Bingel from Essen University Hospital.

Tell us your personal story involving the placebo and nocebo effect! Medicine is also shaped by people’s stories. This is why we’re gathering patients’ experiences regarding their own expectations for the Collaborative Research Centre "Treatment Expectation". You can find out more here.