OUTLOOK Towards better patient care: drugs to avoid in 2017 ABSTRACT harm-benefit balance, and the trial design must be relevant. Tailored supportive care is the best ● To help healthcare professionals and patients option when there are no available treatments choose high-quality treatments that minimise the capable of improving prognosis or quality of life, risk of adverse effects, in early 2017 we updated beyond their placebo effect. the list of drugs that Prescrire advises health pro- Rev Prescrire 2017; 37 (400): 137-148 fessionals and patients to avoid. ● Prescrire’s assessments of the harm-benefit bal- ance of new drugs and indications are based on a his is Prescrire’s fifth consecutive annual re- rigorous procedure that includes a systematic and view of “drugs to avoid” (1,2). The drugs reproducible literature search, identification of Tlisted here are clearly more dangerous than patient-relevant outcomes, prioritisation of the sup- beneficial and should therefore not be used. The porting data based on the strength of evidence, aim is to help health professionals choose safe, comparison with standard treatments, and an anal- effective treatments and thereby avoid harming ysis of both known and potential adverse effects. their patients. ● This fifth annual review of drugs to avoid has been extended to cover all drugs examined by A reliable, rigorous and independent Prescrire between 2010 and 2016 and authorised methodology in the European Union, whereas previous reviews only considered drugs marketed in France. We What data sources and methodology do we use identified 91 drugs that are more harmful than to assess the harm-benefit balance of a given drug? beneficial in all the indications for which they have The following review concerns drugs and indica- been authorised in France or in the Europe- tions on which we published detailed analyses in an Union. our French edition over a seven-year period, from 2010 to 2016. Some drugs and indications were ● In most cases, when drug therapy is really examined for the first time, while others were ne cessary, other drugs with a better harm-benefit re-evaluated as new data on efficacy or adverse balance are available. effects became available. All our publications are intended to provide ● Even in serious situations, when no effective health professionals (and thereby their patients) treatment exists, there is no justification for pre- with the clear, independent, reliable and up-to-date scribing a drug with no proven efficacy that pro- information they need, free from conflicts of inter- vokes severe adverse effects. It may be acceptable est and commercial pressures. to test these drugs in clinical trials, but patients Prescrire is structured in such a way as to guar- must be informed of the uncertainty over their antee the quality of the information provided to our PRESCRIRE INTERNATIONAL • APRIL 2017 • VOLUME 26 N° 181 • PAGE 108-1 OUTLOOK subscribers. The Editorial Staff comprise a broad For example, it can be difficult to attribute a specif- range of health professionals working in various ic outcome to a particular drug, as other factors sectors and free from conflicts of interest. We also must be taken into account, including the natural call on an extensive network of external reviewers history of the disease, the placebo effect, the effect (specialists, methodologists, and practitioners rep- of another treatment the patient may not have resentative of our readership), and each article mentioned, or a change in lifestyle or diet. Similar- undergoes multiple quality controls and ly, a doctor who sees an improvement in certain cross-checking at each step of the editorial process patients may be unaware that many other patients (see About Prescrire > How we work at english. have been harmed by the same treatment (3). prescrire.org). Our editorial process is a collective The best way to overcome this subjective bias one, as symbolised by the “©Prescrire” signature. due to non-comparative evaluation of a few pa- Prescrire is also fiercely independent. Our work tients is to prioritise well-conducted clinical studies, is funded solely and entirely by our subscribers. No particularly double-blind randomised trials versus company, professional organisation, insurance sys- standard care (3,4). tem, government agency or health authority has any financial influence whatsoever over the content Serious conditions with no effective treatment: of our publications. patients should be informed of the conse quences of interventions. When faced with a serious condi- Comparison with standard treatments. The tion for which there is no effective treatment, some harm-benefit balance of a given drug has to be con- patients opt to forgo treatment while others are will- tinually re-evaluated as new data on efficacy or ad- ing to try any drug that might bring them even tem- verse effects become available. Likewise, treatment porary relief, despite a risk of serious adverse effects. options evolve as new drugs arrive on the market. When the short-term prognosis is poor, some Not all drugs are equal: some offer a therapeutic health professionals may propose “last-chance” advantage, while others are more harmful than treatments without fully informing the patient of beneficial and should not be used (3). the harms, either intentionally or unwittingly. All Prescrire’s assessments of new drugs and Yet patients in this situation must not be treated indications are based on a systematic and repro- as guinea pigs. It is very useful to enrol patients ducible literature search. The resulting data are then into clinical studies provided they are informed of analysed collectively by our editorial staff, using an the harms and the uncertain nature of the possible established procedure: benefits, and that the results are published in order – Efficacy data are prioritised: most weight is given to advance medical knowledge. to studies providing robust supporting evidence, But patients must be made aware that they have i.e. well-conducted, double-blind, randomised con- the option of refusing to participate in clinical trials trolled trials; or to receive last-chance treatments with an uncer- – The new drug is compared with a carefully cho- tain harm-benefit balance. They must also be reas- sen standard treatment, if one exists (not necessar- sured that, if they do refuse, they will not be aban- ily a drug); doned but will continue to receive the best available – The accent is placed on those clinical endpoints care. Even though they are not aimed at modifying most relevant to the patients concerned. This means the outcome of the underlying disease, supportive that we often ignore surrogate endpoints such as care and symptomatic treatment are key elements simple laboratory markers that have not been shown of patient care. to correlate with a favourable clinical outcome (4,5). By their very nature, clinical trials involve a high degree of uncertainty. In contrast, drugs used for Careful analysis of adverse effects. Adverse ef- routine care must have an acceptable harm-benefit fects can be more difficult to analyse, as they are balance. Marketing authorisation should only be often less thoroughly documented than efficacy, granted on the basis of proven efficacy relative to and this discrepancy must be taken into account. standard care, and an acceptable adverse effect The adverse effect profile of each drug is as- profile: in general, little, if any, extra information on sessed by examining data from clinical trials and efficacy is collected once marketing authorisation animal pharmacotoxicology studies, and any phar- has been granted (3). macological affiliation. The fact that a new drug has been granted mar- keting authorisation does not signify that its 91 authorised drugs more dangerous harm-benefit balance has been fully documented. than beneficial Indeed, rare but serious adverse effects may only emerge after several years of routine use (3). This review lists drugs that have an unfavourable harm-benefit balance in all their authorised indica- Empirical data and personal experience: risk of tions, in other words drugs that should be removed bias. Empirical assessment of a drug’s harm- from the market on account of their toxicity. Drugs benefit balance based on individual experience can with an unfavourable harm-benefit balance in cer- help to guide further research but is subject to tain situations but not in others have not been in- major bias and represents only weak evidence (3,4). cluded. PAGE 108-2 • PRESCRIRE INTERNATIONAL • APRIL 2017 • VOLUME 26 N° 181 OUTLOOK Notable changes in the 2017 update nly one drug from the list of drugs that Prescrire ad - Six of the new products examined by Prescrire in 2016 Ovises health professionals and patients to avoid was have an unfavourable harm-benefit balance in all their withdrawn from the market in 2016: the recombinant urate approved indications, and three of them are cancer drugs: oxidase pegloticase. Its European marketing authorisation, nintedanib for non-small cell lung cancer and for idiopath- for severe gout, was withdrawn at the request of the phar- ic pulmonary fibrosis,olaparib for ovarian cancer, pano- maceutical company concerned (Prescrire Int n° 180). binostat for multiple myeloma, mepolizumab for asthma, ciclosporin eye drops for dry eye disease, and idebenone Panitumumab, varenicline: Prescrire reviewing new for Leber’s hereditary optic neuropathy. data in 2017. The only drugs listed in our 2016 review of drugs to avoid that do not feature in this year’s review are Additions authorised at European level but not market- panitumumab for colorectal cancers and varenicline for ed in France. Prescrire analyses all drugs that receive smoking cessation. This is because we are currently authorisation through European or French marketing re-evaluating their harm-benefit balance in light of new authorisation procedures. In previous years, we only con- data published in 2016. sidered drugs marketed in France when compiling our list of drugs to avoid in order to provide better patient care.