The system in operation since the late 20th cen- tury for stimulating pharmaceutical research and development (R&D) is increasingly showing seri- ous limitations. In particular, the new drugs it pro- duces are unaffordable and often offer only minor or even no benefits to patients. This system is under increasing criticism, not only from non-governmental organisations, but also from international institutions. A number of interesting proposals have been put forward to remedy the flaws in the current system or to estab- lish alternative systems. The European Alliance for Responsible R&D and Affordable Medicines, a coalition gathering con- sumer, patient, and public health organisations, has called for the creation of an R&D system driven by global public health needs that would deliver high-quality, universally accessible and affordable drugs. The first stage would involve: securing afford- able prices in all countries through effective price controls and greater use of the flexibilities written into intellectual property agreements; requiring proof that new drugs represent a therapeutic advance before granting marketing authorisation; and demanding transparency over the costs of pharmaceutical R&D and drug pricing. In the long term, a global mechanism would need to be established, which would include: pro- viding the public funds necessary to support needs-driven approach to pharmaceutical R&D; establishing new methods that "delink" R&D costs from the end price of health products to make them affordable; and creating a global observatory to track R&D spending, identify areas of health needs and encourage coordinated research efforts in areas of high priority. The Council of Europe, the Council of the Euro- pean Union, the World Health Organization (WHO) and the Organization for Economic Cooperation and Development (OECD) are concerned over the price of new drugs in particular and are calling for a partial or complete overhaul of the system. The health technology assessment agencies of Belgium (KCE) and the Netherlands (ZIN) have not shied away from proposing radically new systems for stimulating R&D.

Some people have coagulation abnormalities, collectively referred to as thrombophilia, which increase the risk of thrombosis. What are the most frequently detected thrombophilia? Does throm- bophilia testing after a venous thromboembolic event enable effective adjustment of the treatment strategy?To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The best known inherited thrombophilia includes the factorV Leiden mutation and the prothrombin G20210A mutation. Hereditary deficiency of the anticoagulants protein C, protein S and antithrom- bin are rarer, and less is known about them. Inher- ited thrombophilia increases the risk of venous thromboembolism to varying degrees compared with the general population, but they have not been shown to increase the risk of arterial thrombosis. The most common acquired thrombophilia is the presence of antiphospholipid antibodies.They can occur alone or in conjunction with autoimmune diseases such as systemic lupus erythematosus. Patients with antiphospholipid antibodies are at increased risk of both venous and arterial thrombosis. Venous thromboembolism usually occurs after a precipitating event and in the presence of risk factors. Thrombophilia is just one of the risk factors for venous thrombosis. Venous thrombo- embolism at a young age in a first-degree relative is another risk factor, even in the absence of a detected inherited thrombophilia. No comparative randomised clinical trials have explored the value of thrombophilia testing in helping to make informed treatment decisions following venous thromboembolism. The known thrombophilias do not affect the efficacy of anticoagulants. Knowing that a patient has a thrombophilia has no impact on the choice or dose of anticoagulant. In cases of unprovoked venous thromboembol- ism, the known inherited thrombophilia do not appear to have a tangible impact on the risk of recurrence after discontinuation of anticoagulation. The increased risk of recurrence associated with the presence of antiphospholipid antibodies appears greater than the risk associated with inherited thrombophilia. The estimated magnitude of this increased risk varies across studies. Clinical guidelines only suggest performing thrombophilia testing after a venous thromboem- bolic event in certain situations, for patients with no identified risk factors for recurrence, when the result might influence the decision to continue or stop anticoagulation: testing for inherited thrombophilia if a close relative had unexplained venous thrombosis at a young age, and antiphospholipid antibody testing. The identification of a thrombophilia can lead to overestimating the risk of thrombosis, and underestimating the risk of bleeding in patients receiving anticoagulation. In practice, thrombophilia testing is rarely useful following venous thromboembolism, except perhaps to clarify the risk of recurrence in some patients in whom the thromboembolic event was unexplained, when deciding whether to discon- tinue anticoagulation.

To help healthcare professionals and patients choose high-quality treatments that minimise the risk of adverse effects, in early 2017 we updated the list of drugs that Prescrire advises health pro- fessionals and patients to avoid. Prescire's assessments of the harm-benefit balance of new drugs and indications are based on a rigorous procedure that includes a systematic and reproducible literature search, identification of patient-relevant outcomes, prioritisation of the supporting data based on the strength of evidence, comparison with standard treatments, and an analysis of both known and potential adverse effects. This fifth annual review of drugs to avoid has been extended to cover all drugs examined by Prescrire between 2010 and 2016 and authorised in the European Union, whereas previous reviews only considered drugs marketed in France. We iden- tified 91 drugs that are more harmful than beneficial in all the indications for which they have been authorised in France or in the European Union. In most cases, when drug therapy is really necessary, other drugs with a better harm-benefit balance are available. Even in serious situations, when no effective treatment exists, there is no justification for prescribing a drug with no proven efficacy that provokes severe adverse effects. It may be acceptable to test these drugs in clinical trials, but patients must be informed of the uncertainty over their harm-benefit balance, and the trial design must be relevant. Tailored supportive care is the best option when there are no available treatments capable of improving prognosis or quality of life, beyond their placebo effect.