CEDARS/ASPENS DebatesPublication Exclusive

Are FDA and PhRMA guidelines for providing information too restrictive?

Industry and physicians should be able to provide evidence-based information, even if it is off label, physician says.

We are now in an era of transparency when it comes to medicine and its relationship with the pharmaceutical industry. The Sunshine Act is in place, and the public wants to understand what relationship their physicians have with industry. The pharmaceutical industry is one of the most scrutinized and regulated in the U.S. This regulation does not just apply to industry’s financial relationships with physicians. In addition to regulation of gifts and payments to physicians, industry now is even more restricted on what it tells physicians. Why have we gotten to this point, and has the regulation crossed the line?

First, we need to address the issue of giving misleading information. It goes without saying that a company should not be able to make false claims. While there has been much discussion recently about the FDA restricting industry’s right to freedom of speech by restricting what it tells physicians and the public, clearly this does not apply in this situation. Obviously, misleading information and false claims may put patients at risk and should be restricted. But what if the information is not false? This is where the problem lies.

On-label information

The FDA requires pharmaceutical representatives to discuss only on-label information with physicians. If a physician asks a representative about an off-label use of a medication, the representative typically will direct the physician to the medical affairs office of the company for the answer. The medical affairs department will then dance around the question to provide information without violating the rule. Who does this help? We all know that many medications are commonly used for treatments not listed on the label. In fact, for some medications, the vast majority of usage is off label.

For example, most antibiotic drops typically gain approval for the treatment of bacterial conjunctivitis. Despite the labeling, this indication makes up only a small portion of prescriptions for topical antibiotics. By far, these drops are used for surgical prophylaxis much more than for conjunctivitis. In fact, it would be considered outside of the standard of care to not treat a patient with antibiotics at the time of surgery. If a physician did not use antibiotics perioperatively and the patient developed a postop infection, there is little doubt that the physician would not fare well in a malpractice case. It is below standard of care to not use antibiotics in this off-label fashion. All the while, pharmaceutical companies are prohibited from giving information about the use of their antibiotics for this indication, which may be useful to surgeons and improve patient safety, because use of these drugs in this fashion is off label.

Physician lectures

These restrictions do not apply just to industry. When a physician speaks at a promotional event on behalf of a drug company, he is held to the same standard. When a speaker gives these types of lectures, he is restricted to a specific slide set that has been preapproved by the legal counsel of the company according to PhRMA guidelines and the FDA. The speaker is not permitted to add any slides or additional information to the lecture. He is not allowed to discuss any off-label use of the medication being discussed. Unfortunately, the off-label or atypical uses of these medications are often the subject that the audience is most interested in. It is common for questions to come up regarding these off-label uses. The speaker is typically instructed to immediately state that this is an off-label use and to answer the question quickly and simply. The speaker must then redirect the audience back to the topic and not elaborate on the off-label use beyond the scope of the direct question.

What is the value of the above restriction? Should a physician be restricted from teaching another physician? Often, this information actually is in the best interest of patient safety. A classic example would be the off-label use of Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan).

While Restasis is approved for treatment of dry eye, there are many off-label uses that have been shown to be effective. It is common for me to be asked about these when I speak. One such use, which often comes up, is for the treatment of Thygeson’s keratitis. Restasis has been reported many times to be effective for treatment of this condition. In fact, the American Academy of Ophthalmology’s Practicing Ophthalmologists Learning System, the review course for maintenance of certification, lists cyclosporine second on the list of medical treatments for this condition, just after topical steroids. Clearly, if the AAO feels that it is appropriate to list this as a potential treatment, there is enough evidence to suggest that this is not a false claim. If the audience member does not specifically ask about this use, the speaker is not permitted to discuss this, even though the AAO suggests it as a potential treatment. The physician in the audience may have no idea that Restasis is even an option and therefore may need to keep treating a patient with steroids for months to years. We all know about the risks of prolonged steroid use, such as glaucoma and cataracts. Is it really in the best interest of patient safety to withhold this information from a treating physician?

Withholding information may be a risk

To extend this discussion a step further, when do the FDA guidelines actually limit a physician’s or pharmaceutical company’s freedom of speech? Presumably, the purpose of the rule is to restrict industry from misleading the public to promote sales. The risk of misleading the public is patient safety. Sometimes, withholding information is also a risk to patient safety. We have seen numerous companies reprimanded and heavily fined by the FDA for off-label discussions. The most unfortunate part is that often the off-label information provided was actually evidence based, yet this did not protect the companies. There have been two recent cases of the court system siding with industry against the FDA in these situations by virtue of First Amendment rights. So where does this leave us now, and what would be a good solution?

While I believe we need to keep restrictions about false claims, we also need a better definition of false claims. If the information provided is evidence based, industry should be permitted to discuss it. In fact, one could argue that it has an obligation to do so, if it will lead to improved patient safety. My cynical side fears that at some point a company will be sued for withholding useful information when a patient has a bad outcome, while a medication, which would have helped, was not used because the physician was not aware of this attribute of the medication. Could the physician be sued for withholding a treatment that would have solved the problem even if he was not aware that it was an option? What if he was afraid to use it on his own because it is considered off label and the company never told him that physicians use it in that fashion? Where does this end?

I realize that there is no easy answer, and the situation is not likely to improve any time soon. I also believe that if the FDA truly has patient safety in mind as the primary reason for these restrictions, then it needs to allow industry to report evidence-based findings to allow physicians to understand the treatments so they may offer these to their patients.

Disclosure: Beckman reports he is a consultant to Allergan.

We are now in an era of transparency when it comes to medicine and its relationship with the pharmaceutical industry. The Sunshine Act is in place, and the public wants to understand what relationship their physicians have with industry. The pharmaceutical industry is one of the most scrutinized and regulated in the U.S. This regulation does not just apply to industry’s financial relationships with physicians. In addition to regulation of gifts and payments to physicians, industry now is even more restricted on what it tells physicians. Why have we gotten to this point, and has the regulation crossed the line?

First, we need to address the issue of giving misleading information. It goes without saying that a company should not be able to make false claims. While there has been much discussion recently about the FDA restricting industry’s right to freedom of speech by restricting what it tells physicians and the public, clearly this does not apply in this situation. Obviously, misleading information and false claims may put patients at risk and should be restricted. But what if the information is not false? This is where the problem lies.

On-label information

The FDA requires pharmaceutical representatives to discuss only on-label information with physicians. If a physician asks a representative about an off-label use of a medication, the representative typically will direct the physician to the medical affairs office of the company for the answer. The medical affairs department will then dance around the question to provide information without violating the rule. Who does this help? We all know that many medications are commonly used for treatments not listed on the label. In fact, for some medications, the vast majority of usage is off label.

For example, most antibiotic drops typically gain approval for the treatment of bacterial conjunctivitis. Despite the labeling, this indication makes up only a small portion of prescriptions for topical antibiotics. By far, these drops are used for surgical prophylaxis much more than for conjunctivitis. In fact, it would be considered outside of the standard of care to not treat a patient with antibiotics at the time of surgery. If a physician did not use antibiotics perioperatively and the patient developed a postop infection, there is little doubt that the physician would not fare well in a malpractice case. It is below standard of care to not use antibiotics in this off-label fashion. All the while, pharmaceutical companies are prohibited from giving information about the use of their antibiotics for this indication, which may be useful to surgeons and improve patient safety, because use of these drugs in this fashion is off label.

Physician lectures

These restrictions do not apply just to industry. When a physician speaks at a promotional event on behalf of a drug company, he is held to the same standard. When a speaker gives these types of lectures, he is restricted to a specific slide set that has been preapproved by the legal counsel of the company according to PhRMA guidelines and the FDA. The speaker is not permitted to add any slides or additional information to the lecture. He is not allowed to discuss any off-label use of the medication being discussed. Unfortunately, the off-label or atypical uses of these medications are often the subject that the audience is most interested in. It is common for questions to come up regarding these off-label uses. The speaker is typically instructed to immediately state that this is an off-label use and to answer the question quickly and simply. The speaker must then redirect the audience back to the topic and not elaborate on the off-label use beyond the scope of the direct question.

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What is the value of the above restriction? Should a physician be restricted from teaching another physician? Often, this information actually is in the best interest of patient safety. A classic example would be the off-label use of Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan).

While Restasis is approved for treatment of dry eye, there are many off-label uses that have been shown to be effective. It is common for me to be asked about these when I speak. One such use, which often comes up, is for the treatment of Thygeson’s keratitis. Restasis has been reported many times to be effective for treatment of this condition. In fact, the American Academy of Ophthalmology’s Practicing Ophthalmologists Learning System, the review course for maintenance of certification, lists cyclosporine second on the list of medical treatments for this condition, just after topical steroids. Clearly, if the AAO feels that it is appropriate to list this as a potential treatment, there is enough evidence to suggest that this is not a false claim. If the audience member does not specifically ask about this use, the speaker is not permitted to discuss this, even though the AAO suggests it as a potential treatment. The physician in the audience may have no idea that Restasis is even an option and therefore may need to keep treating a patient with steroids for months to years. We all know about the risks of prolonged steroid use, such as glaucoma and cataracts. Is it really in the best interest of patient safety to withhold this information from a treating physician?

Withholding information may be a risk

To extend this discussion a step further, when do the FDA guidelines actually limit a physician’s or pharmaceutical company’s freedom of speech? Presumably, the purpose of the rule is to restrict industry from misleading the public to promote sales. The risk of misleading the public is patient safety. Sometimes, withholding information is also a risk to patient safety. We have seen numerous companies reprimanded and heavily fined by the FDA for off-label discussions. The most unfortunate part is that often the off-label information provided was actually evidence based, yet this did not protect the companies. There have been two recent cases of the court system siding with industry against the FDA in these situations by virtue of First Amendment rights. So where does this leave us now, and what would be a good solution?

While I believe we need to keep restrictions about false claims, we also need a better definition of false claims. If the information provided is evidence based, industry should be permitted to discuss it. In fact, one could argue that it has an obligation to do so, if it will lead to improved patient safety. My cynical side fears that at some point a company will be sued for withholding useful information when a patient has a bad outcome, while a medication, which would have helped, was not used because the physician was not aware of this attribute of the medication. Could the physician be sued for withholding a treatment that would have solved the problem even if he was not aware that it was an option? What if he was afraid to use it on his own because it is considered off label and the company never told him that physicians use it in that fashion? Where does this end?

I realize that there is no easy answer, and the situation is not likely to improve any time soon. I also believe that if the FDA truly has patient safety in mind as the primary reason for these restrictions, then it needs to allow industry to report evidence-based findings to allow physicians to understand the treatments so they may offer these to their patients.

Disclosure: Beckman reports he is a consultant to Allergan.