ABSTRACT:
Prescribing off-label medications is commonplace in the field of medicine. Despite the indisputable value of off-label uses and the corresponding need for doctors and other prescribers to be informed about them, the FDA has categorically banned manufacturers of drugs and devices from promoting their use for unapproved purposes to the medical profession. Here, we summarize and discuss the risks and benefits of off-label promotion and how this relates to pharmaceutical companies in the RARE disease space and personalized medicine.

Introduction:
Therapeutics are often found to have additional benefits for uses that exceed those listed on its FDA approved label. This off-label use often includes treatments for disorders that the therapeutic was not initially investigated for by the FDA, dosages or delivery mechanisms that have not been approved, or use of the therapeutic in a patient population that was the focus of the clinical study. Conducting a clinical trial for each indication of the therapeutic could cost a company millions of dollars and lasts for an average of 8 to 12 years, making it infeasible or illogical for a company to conduct clinical trials for every possible indication of the therapeutic. (1)

The FDA began cracking down on pharmaceutical companies’ promotion of off-label use in 1968, after members of Congress became concerned with the Methotrexate scandal. The FDA was made aware of a medical journal article that encouraged physicians to suggest to their patients the off-label use of Methotrexate, which members of Congress believed was linked to the recent deaths from the therapeutic. Congress began pressuring the FDA to develop a clear policy on off-label use by physicians, but the medical community fought the FDA’s efforts.(1) Under the pressure of Congress and the medical community, the FDA decided to focus on the “dissemination of information about off-label use by the product manufacturers, and not the use itself. “

The FDA argues that legalization of off-label promotion will lead to an increase in false and misleading labeling, resulting in less effective and safe medication. Pharmaceutical companies have argued that these therapies have already undergone a phase 1 clinical trial, proving their safety, and that it has a right to disseminate information if it has data that truthfully shows its effectiveness. This assumes that therapies that have undergone its rigorous process are safer and more effective than off-label therapies, which is not an absolute truth. Merck’s blockbuster anti-inflammatory drug Vioxx went through the FDA’s rigorous testing and was approved, but ultimately lead to the death of thousands.(1)

The FDA’s stance on off-label use assumes that physicians are unable to determine what is scientifically and medically substantial. Much of the standard care in oncology have come from doctors prescribing off-label therapies for their patients. In fact, the off-label use of drugs has significantly contributed to the therapeutic armamentarium of many different diseases in medicine.(1) A great example of benefits that have come from off-label use would be aspirin, which is now being used to help reduce the risk of heart attacks. (1)

The effect of the FDA’s stance:
Should we expect a pharmaceutical company to remain silent when it knows that the off-label use of one of its drugs could save the life of a patient with a rare disease?

The FDA’s guidance for the industry restricts communication between industry professionals and physicians, if the indication is not specified within the label. The FDA’s stance could be problematic for a few sectors in the pharmaceutical market such as rare disease. Lives of patients suffering from rare diseases rely on the information that their physicians have access to, and physicians have been shown to have a limited knowledge of many orphan diseases and new treatment options. In the case of rare disease, where the number of patients suffering from the disease rarely exceeds 200,000, the most knowledgeable individuals often work for the pharmaceutical company developing the therapy.(1)

When roughly 90% of the thirty million patients suffering from a rare disease are prescribed at least one drug for off-label use, should we stop the free flow of information and advancement between physician and pharmaceutical company? (1) This would mean that by following the FDA’s guidance, both the physician and pharmaceutical company would be doing a disservice to the very patient population that the guidance was aimed to protect. The current stance of the FDA would leave health professionals and patients in the dark about potential advances. “With diseases of such rarity, proper diagnosis is often a major challenge. Getting appropriate treatment is even harder.” (2) Pharmaceutical companies should be able to provide information about advances in the rare disease, giving doctors more treatment choices for the patient. Unfortunately, physicians face a time constraint and are unable to see patients, attend rare disease conferences, and or read every journal for newly released advances.

1. Tim Mackey & Bryan A. Liang, Off-Label Promotion Reform: A Legislative Proposal Addressing Vulnerable Patient Drug Access and Limiting Inappropriate Pharmaceutical Marketing, 45 U. Mich. J. L. Reform 1 (2011).

2. Coleen Klasmeier and Martin Redish – “Off-Label Prescription Advertising, the FDA and the First Amendment: A Study in the Values of Commercial Speech Protection,” American Journal of Law & Medicine, Volume 37, Numbers 2&3 (2011).

What is blockchain?

A blockchain is a virtual decentralized ledger that allows for the adding and tracking of entries. A decentralized ledger is not regulated by a single entity; rather, the decentralized ledger is regulated by a community of individuals, who prevent entries from being modified or removed from the blockchain database. The blockchain database allows for communication, storage, and processing of the entries added by the community. The blockchain database is publicly accessible to those who are interested in reviewing a copy of the entry.

Individuals who contribute to the blockchain’s computing power are given a unique identifier that allows for tracking of entries added to the blockchain database. Members to the blockchain community can use unique identifiers to contract with each other. For example, members of certain blockchains may contract over real estate. The process of contracting between members of the blockchain community is named “Smart Contracts.” Smart contracts are programmed protocols “that facilitate, verify, or enforce the negotiation or performance of a contract, or that make a contractual clause unnecessary.”

Smart contracts help you exchange money, property, shares, or anything of value in a transparent, conflict-free way, while avoiding the services of a middleman. The best way to describe smart contracts is to compare the technology to a vending machine. Ordinarily, you would go to a lawyer or a notary, pay them, and wait while you get the document. With smart contracts, you simply drop a bitcoin into the vending machine (i.e. ledger), and your escrow, driver’s license, or whatever drops into your account. More so, smart contracts not only define the rules and penalties around an agreement in the same way that a traditional contract does, but also automatically enforce those obligations.

Blockchain provides an opportunity to streamline a timely and costly patent process

It typically takes a very long time for a patent to be reviewed and approved.  Traditionally, inventors and patenting agents conduct preliminary research and determine whether an invention should be patented. For an invention to be patentable, the invention must be (1) novel, (2) non-obvious, and (3) useful. To determine whether an invention is novel, an inventor or patenting agent conducts patent research, which could take 1-3 weeks. If there are not conflicting patents, it will take an average of 2-4 weeks to draft the application for the client to review.  Finally, the patent would be reviewed and approved; however, this process could take 32 months to 3 years.

One of the first large costs that an inventor or small business owner obtains is the cost of a patent search.  This occurs when the inventor or small business owner hires an intellectual property attorney to conduct patent searches for prior art. Hiring an intellectual property attorney will cost the inventor or small business owner well over $1,000. The second large fee for drafting a patent comes from the hiring of an IP attorney to handle this complex process. This process will cost the inventor or small business owner anywhere from $2,000 to $20,000 depending on complexity of the invention. Finally, the cost of submitting the patent to the USPTO can range from a few hundred to a few thousand depending on the invention. These costs can be cumbersome to a small business owner and inventor trying to patent their invention.

 

Using blockchain to automate the patent application can decrease the overall time and cost

The patent application process is one of the best possible uses for a blockchain platform because it would enable inventers and small business owners to save on cost, facilitate faster transactions with the USPTO, and give greater transparency to processes. Searching for patents can be a difficult task because each country or region records its own patents in a closed off registry. A patent blockchain would provide a database for patents globally, opening searches of patents in America and abroad. A patent blockchain would also allow access to prior art globally, resulting in a decrease in patent searching cost and the time a patent examiner spends on that patent. Finally, blockchain would allow for an integrated, cloud based collaborative platform that would automate and streamline the patent application process.

Blockchain would have the capacity of cutting prosecution and processing time of the patent application by weeks, while still retaining the quality. Blockchain has the unique opportunity to ease patenting cost for inventors and small business owners so that more capitol can be spent on developing the invention or marketing. Blockchain also has the capacity of cutting the number of litigation cases by prevent duplication of similar patents. Therefore, blockchain provides endless opportunities to field of intellectual property, including but not limited to my next topic smart contracts and licensing.