Avoiding Physician Liability for Off-Label Use of Drugs and Devices

This month, we continue our discussion with an anlysis of attacks on the physician's decision to prescribe off-label.

Generally, the most common potential liability for off-label prescriptions will be a malpractice or negligence claim, in which the patient attacks the physician's decision, in her medical judgment, that a particular off-label use was appropriate for a particular patient. See Paul D. Rheingold & David B. Rheingold, Offense or Defense? Managing the Off-Label Use Claim, 37 Trial, Mar. 2001, at 52-55. The threat of malpractice liability effectively limits physicians' considerations of more obscure or extreme off-label uses for drugs and devices, because the physician must still show that the off-label use was an appropriate exercise of medical judgment given the information available to him or her at the time. In order to prevail on a malpractice or negligence claim in this scenario, the patient will be required to show that the physician's decision to use the drug or device in that manner failed to comport with “the skill and knowledge normally possessed by members of [the medical] profession ' in good standing in similar communities.” Restatement (Second) of Torts ' 299A (1965). The applicable standard of care is usually interpreted to be a national standard rather than local. See, e.g., Logan v. Greenwich Hospital Ass'n, 465 A.2d 294, 301 (Conn. 1983) (noting that many states have abandoned locality restrictions in favor of a national standard of care).

Expert Testimony

Generally, expert testimony regarding the applicable standard of care within the physician defendant's community of medical peers is required to support a medical malpractice claim. Where the plaintiff is attacking the physician's decision to prescribe a drug or device in an off-label manner, these experts will be called upon to establish that other reasonable physicians in similar circumstances would not have made the decision to use the drug or device in the off-label manner, and that the decision to use it this way caused or contributed to the injuries alleged.

However, the prescribing physician can point to knowledge of the patient's individual circumstances that made him an appropriate candidate for the off-label use, as well as information regarding risks and benefits of that off-label use that he has obtained through medical literature or first person accounts from colleagues in the field. These factors will allow the physician to demonstrate that his decision was reasonable given the information available at the time, rather than with benefit of hindsight at trial.

In addition, consider whether the plaintiff's expert may be shown to be overly rigid. Many experts who are resistant to considering off-label uses of drugs and devices on principle can be made to appear old-fashioned and behind the times on cross-examination at deposition or trial, particularly if the off-label use has become commonplace within their field and yet they still refuse to use it.

When Off-Label Use Becomes the Standard of Care

In certain circumstances, off-label uses of drugs or devices may become so routine within a particular medical community that they become part of the standard of care. See, e.g., Richardson v. Miller, 44 S.W.3d 1, 13 n. 11 (Tenn. Ct. App. 2000) (“because the pace of medical discovery runs ahead of the FDA's regulatory machinery, the off-label use of some drugs is frequently considered to be 'state-of-the-art' treatment ' and may even define the standard of care.”); Southard v. Temple Univ. Hosp., 781 A.2d 101, 104 (Pa. 2001) (off-label use of bone screws with spinal fixation devices had become standard of care within the applicable surgical community). There are numerous examples of when expanded off-label uses of approved drugs led to discovery of additional safe and effective uses, including the preventive use of beta blockers following myocardial infarction, use of Viagra to treat erectile dysfunction, and use of AZT for treatment of AIDS. See Santosh V. Coutinho, License to Promote, or Just What the Doctor Ordered? The New FDA Guidance on Dissemination of Off-Label Reprints by Pharmaceutical Companies, 28 Temp. J. Sci. Tech. & Envtl. L. 279, 289 (2009) (internal citations omitted). These and other similar examples may prove to be powerful evidence both of the importance of physician consideration of off-label uses, and also evidence that failure to consider off-label uses may fall below the standard of care.

Where there is no FDA-approved treatment for a particular condition, but a physician is aware that his colleagues have successfully treated it with an off-label combination of prescription medications, that physician may risk breaching the applicable standard of care if he does not consider using the treatment in a patient who could benefit from it. The physician cannot necessarily rely on the lack of approved treatment options as a reason to abandon attempts to treat the condition, particularly where the plaintiff will be able to find expert witnesses who will note that the off-label treatments are common knowledge within the field. Courts are likely to acknowledge that regulatory approval may lag for years behind the common adoption of an innovative off-label use within a field. See William J. Christopher, Off-label Drug Prescription: Filling the Regulatory Vacuum, 48 Food & Drug L. J. 247, 261 (1993) (“the FDA ' could not review drugs in its lengthy testing process at a pace equal to that at which physicians discover beneficial off-label uses.”) Thus, a physician has an obligation as part of staying abreast of the latest developments and innovations within his field to consider off-label uses that have demonstrated success among his colleagues or in medical literature.

Approved Indications

The approved indications for use of a drug or device as described in the labeling often include a description of patient populations that were excluded from the clinical trial that the FDA relied upon in determining safety and effectiveness, and thus the FDA's approval of the drug or device specifically excludes use in those populations. The most common circumstances in which a patient might allege that the standard of care required consideration of off-label uses is where the patient meets one of these “exclusion criteria” from the clinical trial as described in the product labeling. For example, product labeling may indicate that a drug or device should not be used in patients within certain age groups, or in pregnant women, or in patients with specific past medical histories or other complicating factors. In such circumstances, the physician may not be able to rely on the warnings that the safety and effectiveness had not been established in those populations that are not routinely included in clinical trials, because the patient may nevertheless benefit from the treatment approved for other populations.Where the physician commonly uses that drug or device in his other patients, a patient who is not provided that treatment option because she meets the exclusion criteria of the underlying clinical trial as described in the labeling could argue the physician should have weighed the benefits and risks of attempting the off-label use in that patient.

Physicians may wish to defend such claims by arguing that the safety and effectiveness of off-label uses has not been determined, because they have not made it through the rigorous FDA approval process. It is true that some off-label uses lack sufficient data to support their safety and effectiveness, but the physician is unlikely to prevail using this argument, precisely because the off-label uses of drugs and devices are so common in nearly every medical specialty. It will not be a challenge for a plaintiff to find an expert within the field who can testify generally as to the common practice of employing off-label uses of drugs and devices based upon first person success stories from colleagues or reports in the literature of off-label successes. Physicians defending against a malpractice claim based upon failure to attempt off-label use of a drug or device should focus on patient-specific reasons why the treatment was not appropriate for that particular patient in those circumstances. They should also highlight any significant differences between the patient at issue and those patients involved in prior, reportedly successful, instances of that off-label use. Patient-specific reasons for making a medical decision are much more difficult for experts to refute than attacks on the wisdom of off-label treatments generally.

Disclosure of Regulatory Status As Part of Informed Consent

While numerous plaintiffs have attempted to impose liability on physicians who failed to inform them that a drug or device they received was being used in an off-label manner, this claim has only rarely succeeded. Most courts have found that a physician has no duty to inform a patient that his or her drug or device has been prescribed in an off-label manner as part of obtaining informed consent. See, e.g., Alvarez v. Smith, 714 So.2d 652, 653 (Fla. Ct. App. 1998) (finding that “the majority of reported cases hold that as a matter of law doctors are not required to disclose the FDA status of pedicle screws because such status is not a medical risk of surgery”); Weaver v. Reagen, 886 F.2d 194, 198 (8th Cir. 1989) (holding that regulatory status of a drug “does not necessarily bear on those uses ' established within the medical and scientific community as medically appropriate”); Klein v. Biscup, 109 Ohio App. 3d 855, 864 (Ohio Ct. App. 1996) (noting that “the decision of whether to use a drug for an off-label purpose is a matter of medical judgment, not of regulatory approval”).

However, some courts have refused to grant summary judgment on malpractice claims premised upon an alleged failure to disclose regulatory status during the informed consent counseling process. See, e.g., Shadrick v. Coker, 963 S.W.2d 726, 734-35 (Tenn. 1998) (affirming denial of summary judgment because a disputed issue of material fact remained as to whether the standard of care required disclosure of regulatory status of pedicle screws); Corrigan v. Methodist Hospital, 869 F. Supp. 1202, 1207 (E.D. Pa. 1994) (denying summary judgment because a disputed issue of material fact remained whether knowledge of the regulatory status of the device would have caused the patient to choose a different treatment). While these cases are the exception, in jurisdictions where there is no precedent on this issue, a plaintiff may still artfully plead a claim that may survive summary judgment by alleging that the lack of FDA approval of the use the physician sought to employ was a material fact that should have been disclosed as part of obtaining consent to use of the drug or device.

In some instances, the FDA-approved labeling for the drug or device may assist the physician with defense of informed consent claims. In addition to the FDA-approved indications for use that must be included in all product labeling, the labeling also often makes clear through the contraindications and warning sections that certain particular uses are not approved. For example, the labeling may provide warnings regarding the use of the product for certain patient populations (i.e., “use of this medication has not been studied in pediatric patients”) or the labeling may provide warnings regarding certain unapproved implantation configurations for medical devices (i.e., “the safety and effectiveness of bilateral implantation of this device has not been determined”). Many manufacturers also include this language in their patient literature provided to physicians to give to their patients who may be considering the drug or device. Where the physician provided labeling or literature containing such specific information to the patient before obtaining informed consent, the physician may argue that the patient actually possessed information that informed him that the specific use was outside the FDA-approved indications; thus the regulatory status was actually disclosed prior to informed consent.

Most states have held, in adopting the learned intermediary doctrine, that it is generally the physician's duty, rather than the manufacturer's, to determine what information contained within the FDA-approved labeling should be passed on to the patient as part of obtaining informed consent. See, e.g., Larkin v. Pfizer Inc., 153 S.W.3d 758 (Ky. 2004) (outlining the history of the learned intermediary doctrine adopted by a majority of state courts and federal courts); see also Restatement (Third) of Torts: Prod. Liab. ' 6 (1998) (applying learned intermediary doctrine to medical devices). The manufacturer's duty to warn is satisfied when it provides FDA-approved warnings in the labeling for the drug or device to the learned intermediary physician, and the manufacturer has no duty to warn the patient. See, e.g., McCombs v. Synthes, (U.S.A.), 587 S.E.2d 594 (Ga. 2003). Once the physician has been informed of the risks associated with use of a drug or device, the duty to warn the patient of material risks associated with its use becomes the sole responsibility of the prescribing physician. Id. Because the physician remains responsible for ensuring warnings contained in the labeling are passed on to and appreciated by the patient, the physician may not be able to rely upon the patient's having received the labeling or literature if he did not ensure the patient read, understood and appreciated that the proposed use was unapproved.

Lori G. Cohen, a member of this newsletter's Board of Editors, is a shareholder with Greenberg Traurig, LLP. She focuses on litigation and trial work for the pharmaceutical and medical device industries, products liability, and medical malpractice. She has been recognized by the National Law Journal as one of “The 50 Most Influential Women Lawyers in America” and “Top 40 Under 40.” Sara K. Thompson is of counsel with Greenberg Traurig, LLP and focuses her practice on pharmaceutical and medical device products liability litigation, as well as medical malpractice litigation.

This month, we continue our discussion with an anlysis of attacks on the physician's decision to prescribe off-label.

Generally, the most common potential liability for off-label prescriptions will be a malpractice or negligence claim, in which the patient attacks the physician's decision, in her medical judgment, that a particular off-label use was appropriate for a particular patient. See Paul D. Rheingold & David B. Rheingold, Offense or Defense? Managing the Off-Label Use Claim, 37 Trial, Mar. 2001, at 52-55. The threat of malpractice liability effectively limits physicians' considerations of more obscure or extreme off-label uses for drugs and devices, because the physician must still show that the off-label use was an appropriate exercise of medical judgment given the information available to him or her at the time. In order to prevail on a malpractice or negligence claim in this scenario, the patient will be required to show that the physician's decision to use the drug or device in that manner failed to comport with “the skill and knowledge normally possessed by members of [the medical] profession ' in good standing in similar communities.” Restatement (Second) of Torts ' 299A (1965). The applicable standard of care is usually interpreted to be a national standard rather than local. See, e.g., Logan v. Greenwich Hospital Ass'n , 465 A.2d 294, 301 (Conn. 1983) (noting that many states have abandoned locality restrictions in favor of a national standard of care).

Expert Testimony

Generally, expert testimony regarding the applicable standard of care within the physician defendant's community of medical peers is required to support a medical malpractice claim. Where the plaintiff is attacking the physician's decision to prescribe a drug or device in an off-label manner, these experts will be called upon to establish that other reasonable physicians in similar circumstances would not have made the decision to use the drug or device in the off-label manner, and that the decision to use it this way caused or contributed to the injuries alleged.

However, the prescribing physician can point to knowledge of the patient's individual circumstances that made him an appropriate candidate for the off-label use, as well as information regarding risks and benefits of that off-label use that he has obtained through medical literature or first person accounts from colleagues in the field. These factors will allow the physician to demonstrate that his decision was reasonable given the information available at the time, rather than with benefit of hindsight at trial.

In addition, consider whether the plaintiff's expert may be shown to be overly rigid. Many experts who are resistant to considering off-label uses of drugs and devices on principle can be made to appear old-fashioned and behind the times on cross-examination at deposition or trial, particularly if the off-label use has become commonplace within their field and yet they still refuse to use it.

When Off-Label Use Becomes the Standard of Care

In certain circumstances, off-label uses of drugs or devices may become so routine within a particular medical community that they become part of the standard of care. See, e.g., Richardson v. Miller , 44 S.W.3d 1, 13 n. 11 (Tenn. Ct. App. 2000) (“because the pace of medical discovery runs ahead of the FDA's regulatory machinery, the off-label use of some drugs is frequently considered to be 'state-of-the-art' treatment ' and may even define the standard of care.”); Southard v. Temple Univ. Hosp. , 781 A.2d 101, 104 (Pa. 2001) (off-label use of bone screws with spinal fixation devices had become standard of care within the applicable surgical community). There are numerous examples of when expanded off-label uses of approved drugs led to discovery of additional safe and effective uses, including the preventive use of beta blockers following myocardial infarction, use of Viagra to treat erectile dysfunction, and use of AZT for treatment of AIDS. See Santosh V. Coutinho, License to Promote, or Just What the Doctor Ordered? The New FDA Guidance on Dissemination of Off-Label Reprints by Pharmaceutical Companies, 28 Temp. J. Sci. Tech. & Envtl. L. 279, 289 (2009) (internal citations omitted). These and other similar examples may prove to be powerful evidence both of the importance of physician consideration of off-label uses, and also evidence that failure to consider off-label uses may fall below the standard of care.

Where there is no FDA-approved treatment for a particular condition, but a physician is aware that his colleagues have successfully treated it with an off-label combination of prescription medications, that physician may risk breaching the applicable standard of care if he does not consider using the treatment in a patient who could benefit from it. The physician cannot necessarily rely on the lack of approved treatment options as a reason to abandon attempts to treat the condition, particularly where the plaintiff will be able to find expert witnesses who will note that the off-label treatments are common knowledge within the field. Courts are likely to acknowledge that regulatory approval may lag for years behind the common adoption of an innovative off-label use within a field. See William J. Christopher, Off-label Drug Prescription: Filling the Regulatory Vacuum, 48 Food & Drug L. J. 247, 261 (1993) (“the FDA ' could not review drugs in its lengthy testing process at a pace equal to that at which physicians discover beneficial off-label uses.”) Thus, a physician has an obligation as part of staying abreast of the latest developments and innovations within his field to consider off-label uses that have demonstrated success among his colleagues or in medical literature.

Approved Indications

The approved indications for use of a drug or device as described in the labeling often include a description of patient populations that were excluded from the clinical trial that the FDA relied upon in determining safety and effectiveness, and thus the FDA's approval of the drug or device specifically excludes use in those populations. The most common circumstances in which a patient might allege that the standard of care required consideration of off-label uses is where the patient meets one of these “exclusion criteria” from the clinical trial as described in the product labeling. For example, product labeling may indicate that a drug or device should not be used in patients within certain age groups, or in pregnant women, or in patients with specific past medical histories or other complicating factors. In such circumstances, the physician may not be able to rely on the warnings that the safety and effectiveness had not been established in those populations that are not routinely included in clinical trials, because the patient may nevertheless benefit from the treatment approved for other populations.Where the physician commonly uses that drug or device in his other patients, a patient who is not provided that treatment option because she meets the exclusion criteria of the underlying clinical trial as described in the labeling could argue the physician should have weighed the benefits and risks of attempting the off-label use in that patient.

Physicians may wish to defend such claims by arguing that the safety and effectiveness of off-label uses has not been determined, because they have not made it through the rigorous FDA approval process. It is true that some off-label uses lack sufficient data to support their safety and effectiveness, but the physician is unlikely to prevail using this argument, precisely because the off-label uses of drugs and devices are so common in nearly every medical specialty. It will not be a challenge for a plaintiff to find an expert within the field who can testify generally as to the common practice of employing off-label uses of drugs and devices based upon first person success stories from colleagues or reports in the literature of off-label successes. Physicians defending against a malpractice claim based upon failure to attempt off-label use of a drug or device should focus on patient-specific reasons why the treatment was not appropriate for that particular patient in those circumstances. They should also highlight any significant differences between the patient at issue and those patients involved in prior, reportedly successful, instances of that off-label use. Patient-specific reasons for making a medical decision are much more difficult for experts to refute than attacks on the wisdom of off-label treatments generally.

Disclosure of Regulatory Status As Part of Informed Consent

While numerous plaintiffs have attempted to impose liability on physicians who failed to inform them that a drug or device they received was being used in an off-label manner, this claim has only rarely succeeded. Most courts have found that a physician has no duty to inform a patient that his or her drug or device has been prescribed in an off-label manner as part of obtaining informed consent. See, e.g. , Alvarez v. Smith , 714 So.2d 652, 653 (Fla. Ct. App. 1998) (finding that “the majority of reported cases hold that as a matter of law doctors are not required to disclose the FDA status of pedicle screws because such status is not a medical risk of surgery”); Weaver v. Reagen , 886 F.2d 194, 198 (8th Cir. 1989) (holding that regulatory status of a drug “does not necessarily bear on those uses ' established within the medical and scientific community as medically appropriate”); Klein v. Biscup , 109 Ohio App. 3d 855, 864 (Ohio Ct. App. 1996) (noting that “the decision of whether to use a drug for an off-label purpose is a matter of medical judgment, not of regulatory approval”).

However, some courts have refused to grant summary judgment on malpractice claims premised upon an alleged failure to disclose regulatory status during the informed consent counseling process. See, e.g., Shadrick v. Coker , 963 S.W.2d 726, 734-35 (Tenn. 1998) (affirming denial of summary judgment because a disputed issue of material fact remained as to whether the standard of care required disclosure of regulatory status of pedicle screws); Corrigan v. Methodist Hospital , 869 F. Supp. 1202, 1207 (E.D. Pa. 1994) (denying summary judgment because a disputed issue of material fact remained whether knowledge of the regulatory status of the device would have caused the patient to choose a different treatment). While these cases are the exception, in jurisdictions where there is no precedent on this issue, a plaintiff may still artfully plead a claim that may survive summary judgment by alleging that the lack of FDA approval of the use the physician sought to employ was a material fact that should have been disclosed as part of obtaining consent to use of the drug or device.

In some instances, the FDA-approved labeling for the drug or device may assist the physician with defense of informed consent claims. In addition to the FDA-approved indications for use that must be included in all product labeling, the labeling also often makes clear through the contraindications and warning sections that certain particular uses are not approved. For example, the labeling may provide warnings regarding the use of the product for certain patient populations (i.e., “use of this medication has not been studied in pediatric patients”) or the labeling may provide warnings regarding certain unapproved implantation configurations for medical devices (i.e., “the safety and effectiveness of bilateral implantation of this device has not been determined”). Many manufacturers also include this language in their patient literature provided to physicians to give to their patients who may be considering the drug or device. Where the physician provided labeling or literature containing such specific information to the patient before obtaining informed consent, the physician may argue that the patient actually possessed information that informed him that the specific use was outside the FDA-approved indications; thus the regulatory status was actually disclosed prior to informed consent.

Most states have held, in adopting the learned intermediary doctrine, that it is generally the physician's duty, rather than the manufacturer's, to determine what information contained within the FDA-approved labeling should be passed on to the patient as part of obtaining informed consent. See, e.g., Larkin v. Pfizer Inc. , 153 S.W.3d 758 (Ky. 2004) (outlining the history of the learned intermediary doctrine adopted by a majority of state courts and federal courts); see also Restatement (Third) of Torts: Prod. Liab. ' 6 (1998) (applying learned intermediary doctrine to medical devices). The manufacturer's duty to warn is satisfied when it provides FDA-approved warnings in the labeling for the drug or device to the learned intermediary physician, and the manufacturer has no duty to warn the patient. See, e.g., McCombs v. Synthes, (U.S.A.), 587 S.E.2d 594 (Ga. 2003). Once the physician has been informed of the risks associated with use of a drug or device, the duty to warn the patient of material risks associated with its use becomes the sole responsibility of the prescribing physician. Id. Because the physician remains responsible for ensuring warnings contained in the labeling are passed on to and appreciated by the patient, the physician may not be able to rely upon the patient's having received the labeling or literature if he did not ensure the patient read, understood and appreciated that the proposed use was unapproved.

Lori G. Cohen, a member of this newsletter's Board of Editors, is a shareholder with Greenberg Traurig, LLP. She focuses on litigation and trial work for the pharmaceutical and medical device industries, products liability, and medical malpractice. She has been recognized by the National Law Journal as one of “The 50 Most Influential Women Lawyers in America” and “Top 40 Under 40.” Sara K. Thompson is of counsel with Greenberg Traurig, LLP and focuses her practice on pharmaceutical and medical device products liability litigation, as well as medical malpractice litigation.