Off-label use means the use of a drug „to treat a condition for which it has not been officially approved.“ [1] It is legal under specific conditions (cp. Off-label use: legal aspects) and physicians are free to prescribe them under certain regulations, but they are not clinically tested and evaluated. Off-label use may be reasonable if no drug exists to treat a specific condition or all approved treatments have already failed. [6]
Different interest groups are involved in the off-label use of drugs: health care payers, the pharmaceutical industry, physicians and patients. These different interests are balanced by national laws and institutions, but lead to conflicts because of the disputable use of off-label drugs. Health care payers question paying for unvalidated drugs, physicians want to use the drugs they think are best for the patients’ needs and the pharmaceutical industry wants to increase their sales volume. Patients usually have mixed interests concerning off-label drugs: on the one hand they want the newest therapies, on the other hand they want validated and safe therapies. [2]
Off-label use is quite common: a US survey showed that in the 150 million sampled medications of the survey there was a 21% use of off-label drugs, while 73% of these off-label drugs were not sufficiently scientifically supported. [3]
Economic reasons for not extending the use of drugs to additional conditions
Drugs are limited to specific conditions and their indications. New indications may be added by an additional drug application, but an additional drug application means approving the drug for new uses via a new clinical trial (cp. Clinical trials and new methods undergoing clinical trials), which is very expensive.
Drugs can be brand name drugs or generic drugs. In case of brand name drugs that are used off-label, the companies that own the brand do not experience a financial incentive, as the brand already is known and sold for both the approved and off-label use. Furthermore, the clinical trial could yield nonsupportive results for the off-label use, threatening the already existant off-label business model. In case of the generic drugs – i.e. copied drugs that include the same active pharmaceutical ingredient but are produced by a different company after the original patent expired [4] – the producing companies normally are too small to afford conducting a clinical trial. [2]
Types of off-label use
Because of the previously stated reasons for the not occuring extension of the use of drugs to additional conditions, physicians have to use these drugs off-label. Off-label use may be guideline-recommended, a last-resort therapy or a first-line therapy, with a different corresponding individual responsibility of the involved physician.
The off-labels use is done because of a general presumed drug effect on the patient. This results in several types of off-label use, being:
- off-label use for less severe forms of approved indications,
- off-label use for similar diseases,
- off-label use for a different disease which possesses indications similar to the approved indications,
- off-label use for a different disease that share a physical connection.
Benefits
The benefits of the off-label use of drugs are as follows:
- it allows quicker innovation in clinical practice by not sticking to clinical trials,
- it allows patients earlier access to new drugs,
- it allows physicians to try new medications an new arising evidence,
- it may be the only treatment for orphan conditions (i.e. rare diseases which are too rare to make clinical trials for them profitable [5]).
Risks
The risks of the off-label use of drugs are as follows:
- often the off-label usefulness is not sufficiently scientifically supported, [3]
- it does not meet the patient’s expectations that the drugs safety and efficacy were fully tested,
- newer off-label drugs often have higher costs, increasing health care costs,
- pharmaceutical companies are less inclined to invest in clinical trials for new drugs or the approval of new indications if they can just find new uses for old drugs as off-label variants,
- pharmaceutical companies are more inclined to invest in the approval of secondary indications of the original intended indication of a new drug, because secondary indications are less expensive in clinical trials,
- off-label use undermines the idea of using validated drugs,
- physicists are often influenced by journal articles sponsored by the pharmaceutical industry that feature specific off-label usages, but the presented trials often are only placebo-controlled (no comparison with the regular therapy) and of a general limited quality.