The off-label use of medication: the latest on the Avastin - Lucentis debacle.

The Avastin - Lucentis debacle illustrates the ethical, policy and legal dilemmas encountered with the off-label use of medication. Ophthalmologists are using intra-ocular injections of Avastin (off-label) to treat age-related macular degeneration (AMD). The off-label use of Avastin is controversial because there are anti-VEGF drugs on the market, authorized for AMD, such as Lucentis. Lucentis is however extremely expensive and costs approximately 50 times more than Avastin. Ophthalmologists did not have the backing of randomized controlled trials, or the blessing of the manufacturer of Avastin. In May 2011 the results from the first year of the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT), a large, randomized clinical trial comparing Lucentis and Avastin, were released. The two-year results were published in April 2012. Respecting efficacy, the results of the drugs were the same. The study was not statistically powerful enough to identify meaningful differences in systemic drug-related adverse events and long-term safety. Ongoing trials in other parts of the world might or might not bring clarity in future. Currently there is conflict on the Avastin-issue between cost-conscious health authorities in EU Member States and the EU drug regulators. There are examples of cost-cutting solutions by health authorities, which risk undermining the fundamental principles of the regulatory framework. In the meantime risk is being shouldered by patients and doctors.

Unforeseen ethical/legal complications with screening tests in the capitation model of medical aid schemes.

In the South African health care system patients/consumers are divided into those who can afford private care and those who rely on state medical assistance. The system is under pressure to fund delivery of medical care to its beneficiaries. We consider the effects of different funding models on medicolegal liability of health professionals serving the private sector. Medical reasons should determine the service rendered. However, financial implications of services rendered and defensive practice of medicine also contribute to treatment received by a patient and its remuneration. Practitioners who commit to delivering a predetermined set of services within a particular time for a predetermined 'lump sum' are only paid for the service specifically requested. Should disease be found other than those contracted for, we argue that inaction with regard to that disease would be deemed to be negligent or unethical according to legal and ethical considerations.

Dissemination of information on the off-label (unapproved) use of medication: a comparative analysis.

"Off-label" in relation to the use of medication means that a medicine is used in another way or for indications other than those specified in its conditions of registration and reflected in its labelling. The off-label use of medication accounts for an estimated 21 per cent of drug use overall and is an important part of mainstream, legitimate medical practice worldwide. In South Africa, legislation prohibits the dissemination of information regarding the off-label use of medication. There are diverging views on whether pharmaceutical companies should be allowed to distribute scientific publications on off-label uses of approved drugs. Current policy in the United States of America (USA) eases restrictions on the dissemination of information of this nature. The prohibitions existing in South Africa, however, are more comparable with those in European countries. After analysing the different legal positions on the issue, it is submitted that pharmaceutical companies should not be allowed to disseminate information on off-label uses, but that the regulatory authority play an active and leading role in providing the latest, objective medical and scientific information, as well as guidelines on the off-label use of medication. Other related recommendations are also made.

Inadequate treatment of pain: time for the South African courts to redress this human rights violation?

In the case of 90 per cent of patients, pain can be relieved adequately, but in 80 per cent of these cases this is not done, despite the fact that effective pain medication is available. More than three decades ago, the under-treatment of pain had already been identified as a major global problem. Human dignity requires that treatable pain be relieved. Although attempts have been made to address this unnecessary human suffering, there are a number of reasons why little progress has been made. Fear of the regulatory authority has been mentioned, but in South Africa this is not the case. A lack of knowledge and archaic views have resulted in the standard practice of mismanaging pain. Diverging views on whether the health care system's failure to treat patient pain adequately needs corrective action by the judiciary will be discussed. An argument will be made out that the courts should reconsider the standard practice and the question of what is reasonable in regard to pain treatment. The "failure to treat pain adequately" should be recognised as a separate and independent form of medical negligence. Other possible causes of action will also be discussed. Improvements in pain management require simultaneous initiatives in medicine, law and ethics.

Clinical, legal and ethical implications of the intra-ocular (off-label) use of bevacizumab (avastin)--a South African perspective.

Choroidal neovascularisation is a potentially visually devastating element of various forms of eye pathology. Recent research has focused on neurovascular age-related macular degeneration (AMD) as a cause. AMD can be classified as being exudative (wet) or atrophic (dry). Wet AMD is characterised by a pathological process in which new blood vessels develop in the choroids, causing leakage of fluid and haemorrhage under the retina and leading to localised serous detachment and loss of central vision. Vascular endothelial growth factor (VEGF) stimulates growth of neovascular membranes. Treatments have until recently yielded disappointing results. Ophthalmologists are using intra-ocular injections of bevacizumab (Avastin), an anti-VEGF, to treat AMD. Avastin appears to be safe and effective in the short term, but its intra-ocular administration is entirely off-label. Avastin is registered for treating metastatic colorectal and breast cancer. The off-label use of medication is an important part of mainstream, legitimate medical practice worldwide. Lawyers representing plaintiffs injured by drugs increasingly encounter off-label use claims. From a legal/ethical point of view the off-label use of medication represents a delicate balance between the statutory regulation of medication and a physician's prerogative to prescribe medication that in his or her medical opinion will be beneficial to the patient. The main reason for the controversy created by the off-label use of Avastin is that there are anti-VEGF drugs on the market that have formal approval for the treatment of AMD (and other eye conditions). Lucentis, for example, is extremely expensive, with treatment cost approximately 50 times that of Avastin. Many patients suffering from AMD and macular oedema cannot afford the registered product. The off-label use of Avastin has passed the innovative or experimental stages, as ophthalmologists have used it regularly and openly for a long time, with good success. Such use therefore cannot be considered careless, imprudent or unprofessional. We submit that an ophthalmologist who omits to inform a patient of the availability of Avastin for this form of treatment may be found to be negligent. Protocols developed by the South African Vitreoretinal Society and endorsed by the Ophthalmological Society of South Africa for administering Avastin and other intra-ocular medication intravitreally should be strictly adhered to.