english.prescrire.org > Annual Prescrire Awards > The Prescrire Awards for 2012 > 2012 Prescrire Awards > New drugs and new indications in 2012 > Sluggish progress, timid measures to protect patients

The Prescrire Awards for 2012

The 2012 Prescrire Awards: a yearly round-up from the editors of independent French journal Prescrire

Prescrire looks back at new drugs and indications in 2012
Sluggish progress, timid measures to protect patients

Prescrire published systematic reviews of 278 new products and indications in its French edition in 2012, including 34 new products with new brand names, 30 new indications for existing products, generics, line extensions, changes in labelling, name and composition.

The pharmaceutical market overrun with "innovations" that do not represent progress
Continuing the trend observed in previous years, few of the new products and indications we reviewed in 2012 represented a significant advance for patients: only 4 drugs enable healthcare professionals to provide better patient care, one of which has been on the market for some years but was reviewed in 2012 after more follow-up (see > Table ). Most of the 18 advances identified were slight and do not substantially change prescribing habits: 14 were rated "possibly helpful". See > Prescrire's Drug Ratings.

The harm-benefit balance of 7 other new products or indications could not be determined due to insufficient data (rated "judgement reserved"). Most of these involve treatment of rare diseases and metastatic melanoma (see > Table).

One in five "innovations" best avoided
Half of the new drugs or indications offer no advantages over existing treatments: 42 out of the 82 were rated "nothing new". Year after year, many new drugs are launched that have no demonstrated advantages over the options already available. And some are shown to be dangerous after they have been in use for a few years.

Even more troubling, the proportion of new products and indications with an unfavourable harm-benefit balance remained high in 2012: 15 out of 82 (about 18%) were rated "not acceptable". These drugs, which should never have been authorised in these indications, join a long list of existing drugs that the health authorities should already have withdrawn, sometimes many years ago (see "Towards better patient care: drugs to avoid", available HERE).

Drug prices continue to rise
When pharmaceutical companies launch new drugs, they seek to secure increasingly high sales prices from governmental agencies (Prescrire Int n° 129). Oncology is one of the fields in which expenditure for drugs has reached disproportionate levels in France: about 3600 euros per month for abiraterone in metastatic prostate cancer (Prescrire Int n° 128); about 4400 euros per month for dasatinib in certain leukaemias (Prescrire Int n° 123); about 2900 euros to 4100 euros per month for everolimus in pancreatic neuroendocrine tumours (Prescrire Int n° 131). Another example is pirfenidone for idiopathic pulmonary fibrosis, which although its harms outweigh its benefits, costs about 2120 euros per month (see May 2013 issue).

The cost of these drugs bears no relation to the progress they represent.

Sustained-release quetiapine, for example, costs 10 to 20 times more than standard treatments, despite having no demonstrated advantages; meanwhile, society pays for the promotion of this expensive neuroleptic (Rev Prescrire n° 339).

Little publicity surrounding drug safety withdrawals
While new drugs are often announced amid much fanfare, market withdrawals tend to receive little publicity.

Pharmaceutical companies and drug regulatory agencies sometimes present patients and healthcare professionals with a fait accompli. In 2012, some products that are still quite useful were withdrawn for economic reasons, including: injectable fusidic acid, one option in certain staphylococcal infections (Rev Prescrire n° 347); and lepirudin, which was an alternative to danaparoid before market release of argatroban (Rev Prescrire n° 348). On occasion, healthcare professionals and patients even have to fight to keep a product on the market, as was the case for Phosphoneuros°, an oral solution containing phosphate, which is useful for certain children with hypophosphataemic rickets (Rev Prescrire n° 348).

A few measures to protect patients
One key responsibility of governmental agencies is to protect patients. They have a number of measures at their disposal to oversee and regulate the pharmaceutical market, in order to ensure that patients are not exposed to unnecessary risks.

Market withdrawal, MA rejection, MA revocation: too rare
Market withdrawal and the revocation, restriction or rejection of a drug's marketing authorisation (MA) are effective measures for protecting patients, but are still too rarely used.

A few decisions were taken in 2012 that reflect a trend towards patient protection: suppositories containing terpenes were contraindicated in children under 30 months of age, due to the risk of seizures (Rev Prescrire n° 340); the neuroleptic metoclopramide, which is approved to relieve nausea and vomiting, was contraindicated in children due to its disproportionate neurological adverse effects, and a metoclopramide oral solution for infants and children was subsequently withdrawn from the French market (Rev Prescrire n° 345 and 340).

In 2012, Prescrire welcomed a few unfavourable opinions issued by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP), concerning: naproxcinod, a non-steroidal anti-inflammatory drug that exposes patients to disturbing risks of hypotension and hepatotoxicity (Prescrire Int n° 129); and sodium oxybate in fibromyalgia, which provokes major dose-dependent neuropsychiatric adverse effects (Prescrire Int n° 133).

The French Transparency Committee fulfilling its role
In France, the National Authority for Health's (HAS) Transparency Committee is responsible for evaluating the therapeutic benefit (Service Médical Rendu) of drugs, especially those for which pharmaceutical companies have applied for reimbursement by the national health insurance system or approval for use in hospitals. When a product's therapeutic benefit is deemed "insufficient", reimbursement must be refused or revoked: a welcome development. But often, it is a stopgap measure that simply reduces the number of patients exposed to a dangerous drug that should not remain on the market.

In 2012, reimbursement for several drugs with unacceptable risks was revoked, including: certain combinations of vasoconstrictors used as decongestants, but not naphazoline + prednisolone (Rev Prescrire n° 350); dronedarone in atrial fibrillation; beta-alanine in hot flushes associated with menopause; ropinirole in restless legs syndrome; trimetazidine in angina and various sensory disturbances; and "vasodilators" in age-related neurosensory cognitive deficits (Rev Prescrire n° 339, 342, 345 and 348).

Information about the risks of drugs: easily missed
Apart from a few announcements issued by health authorities, new information published by regulatory agencies about the risks of drugs is easily missed. Prescrire carefully reads all of the changes made to summaries of product characteristics (SPCs), as well as all the published minutes of the meetings of regulatory agency committees, in order to identify any new information that would be useful in healthcare practice or for patient protection.

A few notable examples unearthed in 2012 are: hepatic risks and hallucinations added to the SPC for agomelatine (Rev Prescrire n° 348); optic neuropathy reported in the EMA's "Procedural steps taken and scientific information after the authorisation" for bortezomib (Rev Prescrire n° 349); serious, including fatal, skin lesions added to the SPC for febuxostat (Rev Prescrire n° 347); abuse and addiction associated with methylphenidate, an amphetamine-like stimulant marketed for attention-deficit hyperactivity disorder, reported in the minutes of a French drug regulatory agency (ANSM) meeting (Rev Prescrire n° 344); deaths and cutaneous and cardiac risks associated with midodrine, reported in the minutes of an ANSM meeting (Rev Prescrire n° 343); and occasionally serious allergic reactions added to the SPC for Saccharomyces boulardii, a probiotic taken for diarrhoea (Rev Prescrire n° 348).

Advertising and marketing: the authorities are too lenient
Drug companies use various strategies to encourage drug consumption. Healthcare professionals and patients cannot rely on the information they provide, given their major conflicts of interest.

In 2012, we exposed several tactics used by pharmaceutical companies that place profits above patients' needs: proposing a pharmacological solution to all health problems (medicalisation of life and disease mongering); using opinion leaders to influence healthcare professionals; and funding "training" for medical students (Rev Prescrire n° 339, 341 and 349).

Some companies have engaged in truly harmful activities, for example: Roche concealed adverse effects, particularly in patients who had died; and GlaxoSmithKline conducted misleading promotional campaigns encouraging offlabel use of its drugs (Rev Prescrire n° 349).

In France, in 2012, before prior approval was required for drug advertising aimed at health professionals, 7 advertisements were banned for serious violations: unethical extension of indications, exaggeration of efficacy, or promotion of off-label use. One of these ads promoted the use of the nonsteroidal anti-inflammatory drug flurbiprofen during pregnancy, which could harm the unborn child (Rev Prescrire n° 340, 342 and 347).

Drug advertising is bad for health, yet the authorities continue to refuse to ban it. In France, in 2012, a small breakthrough was made by requiring prior authorisation of drug advertisements aimed at health professionals (Rev Prescrire n° 347). On the other hand, governmental agencies missed an opportunity to put an end to direct-to-consumer advertising of vaccines (Rev Prescrire n° 350).

All too often, the drug industry's interests continue to take precedence over those of patients and public health.

Putting patients' interests first
In 2012, yet again, any true therapeutic advances were minimal, and did not reverse the trend observed in previous years, leading to the 2011 Prescrire Drug Awards ceremony in which not a single medication was granted an award (Prescrire Int n° 125).

The pharmaceutical market is still overrun with dangerous drugs: we have drawn up a list, based on 3 years of Prescrire reviews, that includes about 80 drugs that should not be prescribed, without waiting for regulatory action (see "Towards better patient care: drugs to avoid", available HERE). The health authorities do not fully appreciate the dangers of these drugs. Regulatory agencies can no longer afford to simply inform patients of the risks or to procrastinate: it is high time these drugs were withdrawn from the market.

Let's hope that 2013 will be the year of major advances in patient protection. 

©Prescrire April 2013