As it has been explained in the previous pages, the usage of off-label prescription drugs is wide spread and commonly use among the doctors. However, few patients are aware that they are being prescribed one of these drugs, and doctors are not required to tell their patients that the drug is off label.
One of the main problems is the lack of information about how to best use the drug other than for what is was approved. A study in 2006 [3] showed the off-label prescribing of common drugs and the scientific support behind. It was accounted that 73% of these uses had little or no scientific support at all.
In oder to widen the knowledge of the drug effect, some health organisations develop treatment guidelines that may offer options including these off-label drug uses. Treatment guidelines are based on information from medical literature, including clinical trials and recommend standard ways to treat certain diseases.
This lack of information about the use and the outcome of off-label drugs, may put also the patients at a higher risk for medication errors, side effects and unwanted drug reactions. Communication between the doctor and the patient is high beneficial in order to weigh the possible risks and benefits of the drug.
The uncertainty among off-label drugs makes insurance companies decline to pay for these treatments. Many companies won't pay for an expensive drug that it is not used in a way that is not listed in the approved label, arguing that it's for experimental use. This is a major issue in cancer treatment, area where off-label use is more spread. However the doctor may be able to send the insurer articles as well as other sources that might support his decision of off-label use.
Barcode diagram showing the number of off-label uses in common diseases and the respective scientific support [3]
Nevertheless, off-label drugs may be provide many benefits, specially in those patients that have already exhausted all other approved options. This is mostly frequent in patients with rare diseases and cancer. The latter is the are where off-label drug use is more common. A drug approved for a certain type of cancer, may also work for other types of tumours. Moreover, the lack of pediatric indications on drug labels due to the low number of clinical trials with children, often lead to off-label prescribing, and thus many drugs indicated only for adults are also used off-label in pediatric patient population.
A study published in 2014 [4] about off-label drug use under the perspective of physicians, patients, pharmaceutical companies and regulatory agencies. In the first case, according to the reasons the physicians prescribe off-label drugs, there is usually no relation between prescribing information approved by regulatory authorities and the up-to-date medical practise. In many cases, there is a delay in granting a regulatory approval of a new indication of a medicine after it was gone through clinical trials and proven its safety and effectiveness. While a drug is undergoing this process, a new indication may be suggested. Sometimes after the off-label use of an approved drug is starting to get recognised as a standard therapy, other beneficial uses of the drug are officially discovered. On the patient side, when the best available therapeutic option fails, it's the patient itself who demands a new approach and often leads to off-label uses. However, when there is no certainty about the scientific validity of the off-label use, then the patient might be exposed to unrestricted experimentation, unknown health risks and/or ineffective medicine.
During the drug development process, a drug might be found effective in many indications, but pharmaceutical companies must select limited indications to pursue further research. The cost in the one of the main factors that decide this number of indications, as the number of patients required and the duration of the trials increase with the number of indications. Pharmaceutical companies are reluctant to include new indications that may further increase the cost and time. Moreover, any delay in getting regulatory approval will shorten the period of marketing for a drug during the drug's patent life.
Furthermore, getting the regulatory approval for new uses of an old drug is also costly and time-consuming. An extra drug application is needed to add the new indications to the drug label, and those indications that are not well supported by clinical trials usually don't get approved by the regulatory bodies. The agencies have to balance the need for a rapid approval for the new indications and the amount of information about the safety and efficacy. Moreover, the developmental cost of new uses of old drug might exceed the benefit of regulatory approval. There might be a lack of funding and conducting expensive clinical trials for a drug that is already commonly used off-label it's a risk that companies don't want to take.
Most of the countries don't have a clear guidance about off-label uses of drugs. This has led to cases where the off-label promotion was based merely on marketing techniques rather than scientific support. This led to many controversies, arising the need of having some guidelines like:
- Furnishing scientific data: pharmaceutical companies may give scientific data about new drugs and new uses of already approved drugs.
- Unsought requests: pharmaceutical companies may offer receptive, non-promotional and valid scientific data in response to unsought request.
- Medical journals articles and reference texts
Bibliography
[1] http://www.webmd.com/a-to-z-guides/features/off-label-drug-use-what-you-need-to-know#1
[3] http://news.stanford.edu/news/2008/april9/med-offlabel-040908.html
[4] G.Sandeep, N.Roopa. 2014. Off-label use of medicine: Perspective of physicians, patients, pharmaceutical companies and regulatory authorities. Journal of Pharmacology and Pharmacotherapeutics. Vol 5. Issue Number 2. Pages 88-92. Available here