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

Abstract

Choroidal neovascularisation is a potentially visually devastating element of various forms of eye pathology. Most of the recent research has been 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 choroid, the layer directly under the retina, in the eye. This causes leakage of fluid and hemorrhage under the retina, leading to localised serous detachment and loss of central vision. Vascular Endothelial Growth Factor (VEGF) has been identified as a culprit in the stimulation of growth of neovascular membranes. Formally recognised treatment options have until recently yielded disappointing results.
Opthalmologists are now using intraocular injections of bevacizumab (Avastin®), an anti-VEGF, to treat (AMD). Avastin appears to be safe and effective in the short term. The intraocular administration of Avastin is however entirely off-label. Avastin® is registered for the treatment of metastatic colorectal and breast cancer.
The off-label use of medication has become an important part of mainstream, legitimate medical practice and is a worldwide phenomenon. Lawyers who represent plaintiffs injured by drugs are also increasingly encountering 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 the prerogative of a physician to prescribe medication which, in his medical opinion will be beneficial to the patient. In this article the following questions are discussed:
• When will the off-label use of medication be negligent and when not?
• What is the evidentiary value of the labeling?
• Should the patient be informed that the medication is prescribed off-label?
The “off-label” use of Avastin® has created significant controversy. The main reason being that there are anti-VEGF drugs on the market which have formal approval for the treatment of AMD (and other eye conditions). Lucentis® is however extremely expensive and the treatment costs are approximately fifty times that of Avastin®. Many patients suffering from AMD and macular oedema cannot afford the registered product.
The “off-label” use of Avastin® has long passed the stages where it could be branded as innovative or experimental. The use thereof by opthalmologists has taken place regularly and openly over quite a period of time, with a fairly high degree of success. Taking all the facts into account the “off-label” use of Avastin® cannot be branded as careless, imprudent or unprofessional. It is submitted that an opthalmologist who omits to inform a patient of the availability of Avastin® for this form of treatment, may be found to be negligent.
Locally, the South African Vitreoretinal Society has developed protocols for the administering of Avastin® and other intra-ocular medication intravitreally. These protocols have been endorsed by the Ophthalmological Society of South Africa and should be strictly adhered to.