For patients, the difference between branded medicines and generics might not always be abundantly clear. If a medicine is marketed under two names, it's only natural to assume that there must be some significant difference between the two products.

In theory, however, the only discernible differences between a branded medicine and its generic counterpart should be the name and packaging used.

In short, when a medicine is released by a manufacturer, it holds the patent to solely produce that drug for a certain period of time: often 15 years. After this patent has expired, other manufacturers are free to make their own versions of this item; but will have to sell it under a different name (in the majority of cases, using the name of the active ingredient).

A notable example is the erectile dysfunction drug Viagra. This was developed and released by Pfizer in 1998, and solely produced by them until 2013 when the patent expired. Since then, the drug has also been sold under the name of the functioning agent, Sildenafil, by various manufacturers. (Interestingly, Pfizer themselves have also entered the market with their own generic version of Sildenafil, perhaps partly due to the fact that the market for the drug is so enormous.)

A generic medicine will contain the same active ingredient as the branded version, and be available in the same dosage amounts. Generic products may also in some cases be subject to the same manufacturing conditions as the original.

So one would assume then, that this means the two will share bioequivalent qualities and function in the same way; having the same rate of efficacy, and presenting the same likelihood of causing (the same) side effects in the user.

However, as we’ll explore in this article, many patients would disagree.

What are the physical differences between them?

Although the active ingredients in a generic medicine may be the same, on occasion the excipient ingredients used in its manufacture may be different. This is why sometimes a generic may vary in appearance next to the original.

Some generic medications may also require longer to disperse in the body due to the ingredients used in the coating being of a different consistency.

But these variances should not (once again, in theory at least) amount to any discernable difference in function.

Patient (and doctor) perception

Given the choice, many patients may prefer to use a branded drug over its generic counterpart. This can sometimes be because they trust the brand or have seen it advertised, or are used to taking the branded version and are reluctant to trial a ‘cheaper’ treatment they see as being even slightly different.

A patient may also be hesitant to switch from a branded medicine to a generic if they’re settled on their current treatment.

A prime example of this is the contraceptive pill.

Several generic versions of popular branded pills exist, but as we know the list of side effects that might be caused by hormonal contraceptives is extensive. Finding a candidate which results in little or no adverse effects can sometimes be a challenge for patient and doctor; I know from personal experience that hesitancy when discussing ‘cheaper’ options after becoming accustomed to a successful branded candidate is to be expected.

But when the essential components of two products are the same, can there be noticeable differences in the way branded medications and generics work?

Before we go any further, it would only be proper for me to disclose my own position on this subject; which is that, in essence, the physical function of branded and generic treatments are the same, and that variances are more rooted in patient perception than they are in the performance of the drug itself.

However, it’s still an interesting topic which is subject to intense debate between patients and healthcare providers, and one we thought might be intriguing to look into in more detail; and to do this, we enlisted the help of MeaMedica.

MeaMedica is a website where patients from all over Europe can rate the medications they are taking in a range of fields, including efficacy, rate and severity of side effects, and overall satisfaction. It carries information on hundreds of medicines, including branded and generics.

Which medicines did the researchers look at?

We asked MeaMedica to analyse reviews of a range of medicines that treat a varied cross-section of different conditions.

So we looked at:

  • Losec (branded) and Omeprazole (generic) for heartburn
  • Microgynon (branded) and Ethinylestradiol/Levonorgestrel (generic), a contraceptive pill
  • Imigran (branded) and Sumatriptan (generic) for migraines
  • Zocor (branded) and Simvastatin (generic) for high cholesterol

There was too little data on the following drugs to conduct a sufficient analysis, however we still thought it might be interesting to look at the information stored on:

  • Zovirax (branded) and Aciclovir (generic) for herpes and cold sores
  • Flagyl (branded) and Metronidazole (generic), an antibiotic

Patients were asked to rate their medicines in four areas:

  • effectiveness
  • incidence of side effects
  • severity of side effects
  • and overall satisfaction

Here’s what the researchers found:

Losec -and -Omeprazole -reviews _0.3

  • Losec was more often rated as very effective
  • Users more often reported a high incidence of side effects for the generic
  • Users more often reported serious side effects for Omeprazole
  • Users were more often dissatisfied overall when using Omeprazole than they were using Losec

Microgynon -30-and -Ethinylestradiol -Levonorgestrel -reviews _0.3

(The researchers noted that while the primary function of contraceptive pills may be to prevent pregnancy, the one-to-five star scale for efficacy still applies, as they can be used to treat menstrual conditions such as excessive menstrual bleeding and irregular periods.)

  • Users more often reported a high incidence of side effects for the generic   
  • Users more often reported serious side effects for the generic   
  • Users were more often dissatisfied when using the generic

Imigran -and -Sumatriptan -reviews _0.3

  • Little difference between the two across each measure
  • Users more often rated Sumatriptan as effective
  • However Imigran was more often rated as very effective

Zocor -and -Simvastatine -reviews _0.3

  • This comparison presented the largest difference in rating between the medicines researched
  • Generic was rated nearly five times more often by users as having no effect
  • Nearly half of users reported that they were very dissatisfied when using the generic, while over half reported that they were very satisfied when using the branded medicine

The following comparisons failed the ‘chi-squared test’ (an analysis used to determine whether a range of data can be applied to formulate an argument for or against a particular hypothesis):

Zovirax -and -Aciclovir -reviews _0.3

  • From a comparatively small respondent pool, this analysis presented too many values with a null outcome to be considered.
  • The little data there is suggests a good level of efficacy for both, although the branded version received more favourable feedback

  • This comparison contained too many values which had 5 or less entries
  • One piece of information we might glean from this is that, because the generic version carries significantly more reviews (161 to 9), it is much more widely issued than the branded version

What do the results tell us?

I must admit that I found the variances between the reviews for branded and generics surprising.

As stated above, it’s been my opinion, and that of consultant pharmacist David Kelly, that the difference in performance between branded and generics is more rooted in patient perception than in the physical makeup of the drugs.

I’m of the view that many of the differences between branded medicines and generics medicines which patients experience can be attributed to individual patient perceptions, beliefs and experiences of the healthcare system.’ David tells us.

'The patient's experience of the consultation in which a certain medicine was prescribed can affect the belief about how effective that medicine is. A medicine is more likely to be accepted by the patient if the consultation was a positive one, for example by having a problem acknowledged and paid attention to and also whether or not the patient felt that they were part of the decision making process. Subsequent changing between brands and different generics manufacturers can then cause feelings of uncertainty for the patient.'

Also, a patient might be more receptive to a branded medicine because they know it has been around longer than the generic version or because the packaging looks like it is a better quality. The colour of the medicine itself might also trigger a particular emotional response, which can then affect the perception of effectiveness.'

An argument could certainly be made that, while active ingredients remain the same, excipients can influence peripheral functions, such as absorption and uptake, but this shouldn’t manifest in any perceptible variance, as David explains:

Medications go through rigorous manufacture and testing processes and all versions of the same medicine must show very similar profiles within narrow margins of equivalence for factors such as the rate of absorption into the body and the levels of drug in the blood that are achieved. It would be my expectation that all versions of a particular medicine would have similar if not identical therapeutic effects.

However,’ David continues, ‘when considering the side effects of a medicine it is conceivable that certain filler agents or colourings (which can vary from one version of a medicine to another) could cause an unwanted reaction in a patient and that may well be specific to a certain version of a medicine.'

Yet, even taking this into consideration, I would never have anticipated that the discrepancy in user experience would be quite so significant as these figures suggest.

One observation I would make is that the two migraine treatments, which are typically used on an on-demand basis in response to the early onset of symptoms, were also the treatments that showed the smallest discrepancy. The long-term treatments, particularly the medicine for high cholesterol, appeared to be those that presented the most conflicting reviews.

Does this suggest that patients are more likely to have a negative experience with a generic medicine when they are using it over the long-term?

Or could it be the case that patients who use medication over the long-term are more knowledgeable about their medicine, and are more likely to be sceptical of generics?

To discuss the results further, we spoke to Pauline Bus PhD, who assembled the data sets for us:

Were you surprised by the findings?

We check all incoming reviews before we put them online, so in the meantime we already get an idea of what the total feeling is. So right now it isn’t a surprise to me. But in general, because all the healthcare professionals say that a generic is exactly the same as the branded version, I understand why it is a surprise to many people.’

If you were to speculate, why do you think there is such a significant gap in scores between some of the branded medicines and their generic counterparts?

We think it might be caused by the different production processes; whether the pill has a coating or not, what kind of excipients are used. There is a lot of freedom in the production processes. As long as the bio-equivalence is within a certain range for a specific period of time the medicine is considered to be the same. However the outer values of this range can already have a big influence on how someone responds to the medicine.’

Another factor that can have quite some influence is that the branded version has had a lot of research to optimize the medicine and add the best excipients, such as coating and so on, to get the desired effect.’

In your experience, is it more common for a generic medicine to score badly compared to its branded counterpart, when it is a long term medicine which has to be taken every day?

When people are using the branded medicine and have to switch to a generic one, or if they already use a generic medicine and then receive a different one, it is possible they notice some differences. We think this will mostly happen with long-term medicines. Short-term medicines often won’t be switched, so they will only have experience with the one they received, so either the branded or the generic one.

Now that you ask this question, I realise that all the medicines in this study can be considered long-term medicines. So I took the liberty of checking some short-term medicines (such as Nitrofurantoin and Furabid) and those seem to be equal.’

Actually, we didn’t check the data for possible switches, so we can’t really say something about the switching-effect. However, with other medicines than the ones considered in this article we also get positive messages from people who switched from a branded medicine to a generic one; either it’s more effective or they have less side effects. So, it can go both ways.’

Obviously the scores in this analysis were issued by patients who knew beforehand whether their medicine was made by a brand or was a generic; so an argument could be made that patient perceptions of branded and generics might be playing a role in the scores. If a blind test scenario was used to compare branded and generics instead, where patients didn't have foreknowledge of which they were taking, do you think the scores would be different?

Our experience is that people are perfectly capable of keeping that part out of the equation. They just want to share what they experience, not just because they want to be negative about their (generic) medicines. In addition, the Dutch side effects centre (Lareb) has done research on the reporting of side effects by patients compared with doctors. The result was that the quality of the outcome was the same, only different words were used. Therefore, we can say that patients know very well how to judge their medicines and the possible side effects.

What is particularly interesting to note is the reverse trend Pauline talks about; that in some cases not considered in our analysis, more patients report favourable experiences when using a generic over its branded counterpart. As such, conducting a more wide-ranging analysis, including several other drug candidates from the MeaMedica database, may tell a significantly different story to the one we’ve presented.

However, I would still hold that a large proportion of patients have the predetermined idea that branded medicines are better than generics, which introduces a degree of prejudice into any comparison containing foreknowledge of the drugs being used.

To be a true analysis of the functional differences between the medicines then, it’s my opinion that such a comparison would need to be undertaken in the form of a double-blinded randomised controlled trial, and involve more participants.