To make it easier to choose quality care, and to prevent disproportionate harms to patients, Prescrire has published its annual update of drugs to avoid. Using a reliable, rigorous and independent methodology, Prescrire's editors identified 93 drugs currently authorised in France or the European Union that are more harmful than beneficial in all the approved indications.
 

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

Prescrire's annual review of "drugs to avoid"  concerns drugs and indications on which we published detailed analyses in our French edition over a nine-year period, from 2010 to 2018. Some drugs and indications were examined for the first time, while others were re-evaluated as new data on efficacy or adverse effects became available.

All our publications are intended 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, 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 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. Likewise, treatment options evolve as new drugs arrive on the market. Some offer a therapeutic advantage, while others are more dangerous than beneficial and should not be used.

All Prescrire’s assessments of drugs and indications are 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 accent is placed on results based on 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, and 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 be overlooked during clinical trials and may only emerge after several years of routine use by many patients.

Empirical data and personal experience: risk of bias

Empirical assessment of a drug’s harm-benefit balance based on individual experience can help to guide further research but is subject to major bias that strongly reduces the level 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 may be unaware that many other patients have been harmed by the same treatment.

The best way to minimise subjective bias caused by non-comparative evaluation of a few patients is to prioritise well-conducted clinical studies, 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 into clinical trials, provided they are informed of the harms and the uncertain nature of the possible benefits, and that the trial results are published 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 they are not aimed at modifying the outcome of the underlying disease, supportive care and symptomatic treatment are useful elements of patient care.

By their very nature, clinical trials involve a high degree of uncertainty. In contrast, 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, extra information on efficacy is collected once marketing authorisation has been granted.

©Prescrire 1 April 2019

free"Towards better patient care: drugs to avoid in 2019" Prescrire Int 2019; 28 (203): 108-1 - 108-10. (Pdf, free)

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