Off-label Use of Medicinal Products in the RF and Abroad

November 23, 2016

BRACE Law Firm ©

Junior Lawyer at BRACE Law Firm Maria Nikitina

The term “off-label” means that a medicinal product is prescribed in a manner not specified in its description: for other diseases, in a different dosage, with a different frequency, for a child instead of an adult, or with any other deviation from the instructions. Turning to the legislation of our country, it can be said that the use of medicinal products off-label is possible. Clause 5 of Article 37 of Federal Law No. 323 “On the Basics of Health Protection of Citizens in the Russian Federation” provides for the “prescription and use of medicinal products not included in the relevant standard of medical care, in the event of medical indications (individual intolerance, for vital indications) by decision of a medical commission”. Furthermore, the mandatory Procedures for providing medical care approved by the Ministry of Health of Russia also do not contain a ban on the use of medicinal products in ways and cases not provided for by the manufacturer’s instructions for use.

Off-label use of medicinal products is most frequently encountered in children and pregnant women. Often, clinical trials are not conducted on these groups of patients due to legislative restrictions (clauses 1, 2 of part 6 of Article 43 of Federal Law No. 61 “On the Circulation of Medicines”), and since manufacturers have not studied the drug in these patient groups, the instructions state that the use of the medicine for them is prohibited. According to 2015 data, 75% of medicines in pediatrics in the RF are used off-label, and in neonatology – up to 90%. Additionally, 90–95% of medicines used in the treatment of pregnant women are also off-label. At the same time, the possibility of side effects is quite high. Restrictions on informing doctors about the possibilities of off-label use create additional risks in such situations, as doctors do not possess sufficient information about all the risks associated with such use.

The next problem is that Russian legislation does not explicitly provide for the liability of a pharmaceutical worker for giving any recommendations for off-label use of a drug. Moreover, in pharmacies, pharmaceutical workers provide consultations orally, and proving the fact that a person suffered from a received recommendation is practically impossible. Civil or criminal liability of a pharmaceutical worker in the event of a recommendation to use a drug off-label can only occur if harm to health is caused by the incorrect use of this drug based on the worker’s recommendation. In this case, both the fact that such a recommendation was given and a direct link between the recommendation and the harm caused to the citizen’s health must be proven.

Off-label Use of Medicines in the USA The off-label use of medicinal products in the USA is not currently prohibited by law. Potential liability for such a prescription rests with the practicing physician. In some complex cases, using a drug off-label may, in principle, be the only possible treatment for a patient. Importantly, in the USA, pharmaceutical companies do not have the right to advertise a drug for off-label use; however, they may publish peer-reviewed articles about such use in medical journals. Currently, the FDA is considering the option of allowing companies to advertise off-label uses of medicines, while trying to account for the possible pros and cons. A consequence of such a change could be the release of pharmaceutical companies from lawsuits related to the promotion of off-label drug use. Over the last 10 years in the USA, there have been at least five court decisions totaling more than a billion dollars related to off-label advertising. In a public opinion poll conducted in the USA, half of the respondents believed that a drug should only be prescribed for its primary, FDA-approved purpose. In turn, half also believe that doctors should be prohibited from prescribing drugs off-label. Notably, the case of the company “Amarin” stands out, which, in a dispute with the FDA, protected its right to inform doctors about studies on off-label use of a drug, provided that such information is truthful and does not mislead doctors. Curiously, the constitutional right to freedom of speech formed the basis of the justification.

Off-label Use of Medicines in the EU As for the EU, not all countries currently have separate provisions regulating the use of drugs for purposes other than their direct indication. For example, such a minority includes France, Spain, Italy, and Great Britain. In Germany, it is established that in order to deviate from recognized medical practice for the use of a particular medicine, one must have a compelling reason for choosing a less safe method, as well as apply additional security measures to minimize possible harm. Swiss federal law establishes that a drug not intended for the treatment of a specific disease can only be used when the disease threatens the patient’s life and if the medicine required for treatment does not exist. Starting this year, pharmaceutical companies operating in the EU will be required to collect and report information on the off-label use of their drugs. This information includes: reporting on the presence of adverse reactions after off-label use of the medicine by patients; periodic reporting on clinically significant risks associated with such use; and risk management planning based on a quantitative assessment of the use of medicines for purposes other than those intended.

The problem of using drugs off-label is global, and there is still no consensus on whether it is truly necessary to use medicinal products off-label, thereby risking the health of patients.

November 23, 2016