english.prescrire.org > Annual Prescrire Awards > The Prescrire Awards for 2019 > Drugs to avoid in the name of better patient care: 2020 update > Drugs to avoid: 2020 update > Drugs to avoid: a reliable, rigorous and independent methodology

The Prescrire Awards for 2019

Drugs to avoid in the name of better patient care: 2020 update

Drugs to avoid in the name of better patient care: 2020 update
Drugs to avoid in the name of better patient care: a reliable, rigorous and independent methodology

Drugs to avoid in 2020 Prescrire's eighth consecutive annual review of drugs to avoid includes documented cases of drugs that are more dangerous than beneficial. The aim is to make it easier to choose safe, effective treatments, primarily to avoid exposing patients to unacceptable harms. The drugs listed (sometimes a particular form or dose strength) should be avoided in all the clinical situations for which they are authorised in France or in the European Union.

"Towards better patient care: drugs to avoid in 2020" Prescrire Int 2020; 29 (212): 51-1 - 51-10.

105 authorised drugs that are more dangerous than beneficial

As of late 2019, based on the drugs examined by Prescrire between 2010 and 2019 that are authorised in France or in the European Union, 105 drugs were identified as more dangerous than beneficial in all their authorised indications. 92 of these drugs are marketed in France. They are listed based first on the therapeutic area in which they are used and then in alphabetical order according to their international nonproprietary names (INNs).

These 105 drugs comprise:
  • Active substances with adverse effects that, given the clinical situations in which they are used, are disproportionate to the benefits they provide;
  • Older drugs that have been superseded by newer drugs with a better harm-benefit balance;
  • Recent drugs that have a less favourable harm-benefit balance than existing options;
  • Drugs that have no proven efficacy beyond that of a placebo, but that carry a risk of particularly severe adverse effects.
The main reasons why these drugs are considered to have an unfavourable harm-benefit balance are explained on a case-by-case basis. When available, better options are briefly mentioned, as are situations (serious or non-serious) in which there is no suitable treatment. The differences between this year's and last year's lists are detailed in > Drugs to avoid: main changes in the 2020 update.

What data sources and methodology do we use to assess a drug's harm-benefit balance?

Our list of drugs to avoid concerns drugs and indications on which we published detailed analyses in our French edition over the 10-year period from 2010 through 2019 inclusive. Some drugs and indications were examined for the first time, while others were re-evaluated as new data on efficacy or adverse effects have become available.

One of the main objectives of our publications is to provide health professionals (and thereby their patients) with the clear, independent, reliable and up-to-date information they need, free from conflicts of interest and commercial pressures.

Prescrire is structured in such a way as to guarantee the quality of the information provided to our subscribers. The Editorial Staff comprise a broad range of health professionals working in various sectors and free from conflicts of interest. We also call on an extensive network of external reviewers (specialists in the relevant area, methodologists, and practitioners representative of our readership), and each article undergoes multiple quality controls and cross-checking at each step of the editorial process (see About Prescrire > How we work). Our editorial process is a collective one, as symbolised by the "©Prescrire" signature.

Prescrire is also fiercely independent. Our work is funded solely and entirely by our subscribers. No company, professional organisation, insurance system, government agency or health authority has any financial (or other) influence whatsoever over the content of our publications.

Comparison with standard treatments

The harm-benefit balance of a given drug has to be continually re-evaluated as new data on efficacy or adverse effects become available. Similarly, treatment options evolve as new drugs arrive on the market.

Some drugs offer a therapeutic advantage, while others are more dangerous than beneficial and should not be used. Prescrire's assessments of drugs and indications are all based on a systematic and reproducible literature search. The resulting data are then analysed collectively by our Editorial Staff, using an established procedure:

  • efficacy data are prioritised: most weight is given to studies providing robust supporting evidence, i.e. double-blind, randomised controlled trials;
  • the drug is compared with a carefully chosen standard treatment, if one exists (not necessarily a drug);
  • the results taken into account are based on the clinical endpoints most relevant to the patients concerned. This means that wherever possible we ignore surrogate endpoints such as laboratory markers that have not been shown to correlate with a favourable clinical outcome.

Careful analysis of adverse effects

Adverse effects can be more difficult to analyse, as they are often less thoroughly documented than efficacy. This discrepancy must be taken into account.

The adverse effect profile of each drug is assessed by examining data from clinical trials and animal pharmacotoxicology studies, and any pharmacological affiliation.

When a new drug is approved, many uncertainties remain. Some rare and serious adverse effects may have been overlooked during clinical trials and may only emerge after several years of routine use by a large number of patients.

Empirical data and personal experience: risk of major bias

Empirical assessment of a drug's harm-benefit balance, based on individual experience, can help to guide further research, but it is subject to major bias that strongly reduces the level of evidence of the findings. For example, it can be difficult to attribute a specific outcome to a particular drug, as other factors must be taken into account, including the natural history of the disease, the placebo effect, the effect of another treatment the patient may not have mentioned, or a change in lifestyle or diet. Similarly, a doctor who sees an improvement in certain patients cannot know how many other patients' conditions worsened when they received the same treatment.

The best way to minimise subjective bias caused by non-comparative evaluation of a few patients is to prioritise the results of clinical trials, particularly double-blind, randomised trials versus standard care.

Serious conditions with no effective treatment: patients should be informed of the consequences of interventions

When faced with a serious condition for which there is no effective treatment, some patients opt to forgo treatment while others are willing to try any drug that might bring them even temporary relief, despite a risk of serious adverse effects.

When the short-term prognosis is poor, some health professionals may propose "last-chance" treatments without fully informing the patient of the harms, either intentionally or unwittingly.

But patients in this situation must not be treated as guinea pigs. "Trials" of drugs belong in the sphere of formal, properly-conducted clinical research, not health care. It is useful of course to enrol patients in clinical trials, provided they are informed of the harms and the uncertain nature of the possible benefits. The trial results should be published (whether positive, negative or inconclusive) in order to advance medical knowledge.

However, patients must always be made aware that they have the option of refusing to participate in clinical trials or to receive "last-chance" treatments with an uncertain harm-benefit balance. They must also be reassured that, if they do refuse, they will not be abandoned but will continue to receive the best available care. Even though the aim of supportive care and symptomatic treatment is not to modify the underlying disease, they are useful elements of patient care.

While there is a great deal of uncertainty surrounding the harm-benefit balance of drugs that are under evaluation in clinical trials, drugs used for routine care must have an acceptable harm-benefit balance. Marketing authorisation should only be granted on the basis of proven efficacy relative to standard care, and an acceptable adverse effect profile: in general, little, if any, additional information on efficacy is collected once marketing authorisation has been granted.

 > FREE PDF  "Towards better patient care: drugs to avoid in 2020" Prescrire Int 2020; 29 (212): 51-1 - 51-10.

©Prescrire 1 February 2020

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