Off-Label Prescribing: What Are the Medical-Legal Risks?
By James E. Szalados, MD, MBA, Esq., Critical Care Medicine, Unity and Via Health Systems, Westside Anesthesiology Associates of Rochester, LLP, Vice President for Medical Affairs Lakeside Health System, Counselor and Attorney at Law, Rochester, NY
Disclaimer: The material presented herein is for educational purposes only and does not represent legal advice. Laws pertaining to the practice of medicine are state-specific; please refer to the statutes and regulations governing the practice of medicine in your specific state of licensure. The views expressed herein are those of the author may not coincide with those of the entities with which this author is affiliated.
You, a licensed medical practitioner, have read a number of recent papers in respectable scientific journals and even attended lectures at medical meetings regarding the use of 'Drug X' in the treatment of patients with a certain medical condition. Now, you are treating a patient that you feel would be a good candidate for 'Drug X.' Unfortunately, 'Drug X' is not indicated by the FDA for the treatment of that specific condition; and, you are unable to find prescribing information regarding the optimal dose or duration of therapy with 'Drug X' for that condition. You realize that your use of 'Drug X' in this circumstance would be considered "off-label." What legal risks, if any, might you face? How could you argue in support of your treatment decision?
Statutory and Regulatory Controls Regulating Pharmaceuticals
The Food and Drug Administration (FDA) is the federal agency empowered by the U.S. Congress with the authority to interpret and enforce the Federal Food, Drug, and Cosmetic Act (FDCA)1 and its amendments. Thus, the FDA has a statutory mandate to regulate the research, approval process, marketing, manufacturing, and distribution of pharmaceuticals, implants, biologics, and combination products within the United States.
The FDA's regulation of new drug development addresses two primary goals that are implied within the agency's mission statement: 1) FDA standards require empiric demonstration of both the safety and efficacy of new drugs prior to their approval for marketing; and 2) enforcement of the regulatory scheme is necessary to preclude unapproved products from entering the market. In addition, the process by which the FDA approves new drugs inevitably reflects a high degree of administrative tension between two competing and important public health risks: 1) a risk of premature approval without adequate demonstration of safety and efficacy; and 2) a risk of undue administrative delay resulting in the unavailability of necessary medications required for the treatment of diseases. The FDA regulates all phases of drug testing in humans and requires data from "adequate and well-controlled" studies to provide "substantial evidence" regarding the safety of a drug and its effectiveness in the treatment of those medical conditions for which it is to be marketed.2
A potential new drug ("New Chemical Entity") first undergoes three phases of clinical testing through a strictly controlled investigational new drug (IND) process.3 If, during the formal IND testing, the data supports an initial presumption of reasonable safety and effectiveness, a manufacturer then may submit a new drug application (NDA) and request FDA approval. The NDA must include statutorily specified and detailed information, including: 1) active and inactive components; 2) manufacturing process; 3) samples; 4) detailed information, which includes data regarding the design and results of scientific studies conducted to determine the drug's safety and efficacy for particular uses; and 5) the proposed labeling for the drug.4 The FDA's fconsideration of an NDA is necessarily limited to the use or uses for which the manufacturer has conducted studies as to safety and efficacy in humans through the clinical trials process.5 In 1997, Congress legislated the Food and Drug Administration Modernization Act (FDAMA).6
Drug Labeling and the FDA
The labeling submitted by a drug manufacturer with the NDA must reflect the intended use or uses of the drug based on the studies conducted and the scientific data available, dose and duration of therapy data, and all known information regarding contraindications, side-effects, interactions, and toxicities. The issue of labeling is fundamental to the process of new drug approval since the FDA will only approve a new drug application (NDA) if the proposed labeling strictly conforms with those uses supported by scientific data and consistent with the "substantial evidence" standard.7 The medical uses for which the manufacturer has conducted clinical trials to establish safety and efficacy are commonly referred to as "indications" a drug used in a manner consistent with the label is being used "as indicated."
Labeling is a legal term that encompasses all the written, printed, or graphic material "(1) upon any [drug or device] or any of its containers or wrappers, or (2) accompanying such [drug or device]."8 The package insert is one form of labeling; however, the term "labeling" also has been legally construed to include nearly every form of promotional activity, including booklets, pamphlets, mailing pieces, bulletins, and all literature that supplements, explains, or is otherwise textually related to the product. The basic labeling rule as promulgated by the FDA is that all material facts relating to the drug are to be presented on the package.9 However, the labeling and compounding of the drug must not be changed since the FDA explicitly prohibits the distribution of drugs that have been subject to "misbranding" or "adulteration."10
Off-Label Prescribing by Physicians: The FDA's Position
It is widely recognized that at the time the NDA application is submitted, FDA approval occurs, and even through subsequent marketing and post-marketing surveillance, the regulatory process cannot possibly account for all the possible clinical uses for a new drug.11 Thus, the position of the FDA is that following approval, the FDA does not attempt to prevent physicians from prescribing any approved drug for clinical indications that deviate from those for which the drug was initially tested and approved. Such uses outside of the formal labeling recommended by the manufacturer and subsequently approved by the FDA are termed off-label uses.
The term "off-label" refers to circumstances in which a physician prescribes a drug to a patient in a manner that varies in some way from the drug's (or device's) FDA-approved labeling. Off-label prescription occurs when a physician prescribes a drug in any manner that varies from labeling specifications (e.g., use for an indication other than for which it was approved, to achieve a different therapeutic effect, prescription of a drug to unapproved patient groups, for periods of use exceeding the labeling recommendations, or in unapproved combination with other FDA-approved drugs). It is important to realize that the term "off-label" represents no more than a regulatory description of the administratively approved use or uses of a medical drug or device. Thus, off-label only references a drug's legal status and does not refer to scientific facts or accepted medical practices.
Neither Congress nor the FDA has attempted to regulate the off-label use of drugs by physicians or consumers. A physician may legally prescribe a legal drug for any purpose that he or she deems appropriate, regardless of whether the drug has been approved for that specific use by the FDA.12 Prescriptive "off-label" usage by physicians "is considered to be an accepted and necessary corollary of the FDA's mission to regulate [pharmaceuticals] without directly interfering with the practice of medicine."13 The FDCA expressly states that "[n]othing in this Act [21 USCS §§ 301 et seq.] shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate health care practitioner-patient relationship."14
The FDA subsequently has formally stated that "'unapproved' or, more precisely, 'unlabeled' uses may be appropriate and rational in certain circumstances, and may, in fact reflect approaches to drug therapy that have been extensively reported in medical literature ... Valid new uses for drugs already on the market are often first discovered through serendipitous observations and therapeutic innovations, subsequently confirmed by well-planned and executed clinical investigations."15
Courts have repeatedly recognized the legitimacy of the off-label use of drugs by physicians.16 The Third Circuit opined on Congressional intent when it noted that "Congress did not want to interfere with physicians' treatment of their patients. New uses for drugs are often discovered after FDA approves the package inserts that explain a drug's approved uses. Congress would have created havoc in the practice of medicine had it required physicians to follow the expensive and time-consuming procedure of obtaining FDA approval before putting drugs to new uses. Thus, Congress exempted the practice of medicine from the Act so as not to limit a physician's ability to treat his patients."17 Finally, a physician's off-label use does not impute hospital liability as under the FDCA.18
Thus, off-label use of drugs (and medical devices) is recognized to be a legitimate part of the practice of medicine and, as a practice, is legal. Off-label uses also are considered to be ethical and are thought to represent neither experimentation nor research. The FDCA defines "clinical investigation" to mean "any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects;" and excluded off-label prescribing, noting that "an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice."19 Furthermore, the courts have found that a treatment found to be "in accordance with generally accepted standards of medical practice" would hardly be "experimental" and similarly, a procedure found to be of "scientifically proven value" would similarly not be "experimental."20
Informed Consent Requirements for Off-Label Use
The majority of court cases hold that FDA status does not represent a "medical risk;" thus, it need not be disclosed in informed consent. This is consistent with the legal theory that FDA status represents legal and administrative status and not necessarily a scientific or medically appropriate status. In Alvarez v. Smith, appellant patient and his wife sought review of the order from the Florida Circuit Court for Orange County that held that a physician did not have a duty to disclose to the patient the "experimental or investigational" FDA status of surgical screws, and that such screws were implanted into his spine without his informed consent. The Florida Court of Appeals noted 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."21 The court went on to say that "a physician is free to use a medical device for an off-label purpose, if, in the physician's medical judgment, he or she believes that use of the device will benefit the patient. Because the off-label use of a medical device is a matter of medical judgment, a physician may be subject to medical malpractice liability for the exercise of that judgment. That physician cannot, however, be held liable under the doctrine of informed consent for failing to advise a patient that a particular device has been given an administrative or regulatory label by the FDA."22
In the case of Betsinger v. Fontana, another case addressing the off-label use of Cytotec (misoprostol), plaintiffs contended that the defendant physician "used Cytotec to facilitate dilation of the plaintiff mother's cervix during the birth process, failed to apply the recommended dosage for such use, and failed to advise the plaintiff that the drug was not approved for such usage by the FDA at that time."23 The mother suffered a uterine rupture and the baby was born profoundly depressed and was later diagnosed with cerebral palsy. Within two months of the delivery, the American College of Obstetricians and Gynecologists (ACOG) issued an advisory to physicians that Cytotec should not be used in patients with prior cesarean-section (c-section) since the risk of uterine rupture posed by the use of the medication in the setting of a potentially weakened uterine wall was an unacceptable risk. This recommendation was based upon four articles published in recognized obstetrical journals; these publications were available at the time that of the plaintiff's delivery. The makers of Cytotec noted that Cytotec "weakens collagen fibers, including scar tissue and, therefore, is not appropriate for use, even in an 'off-label' capacity, in a patient with a previous history of c-section."23 The case settled at mediation approximately one month prior to trial for a structured amount with a total payout value of more than $6 million.
The Law as it Pertains to Marketing Pharmaceuticals for Off-Label Uses
Although physicians are free to prescribe approved pharmaceuticals for off-label uses, manufacturers of pharmaceutical products are explicitly prohibited from marketing or promoting a drug for any use (as opposed to "intended use") not approved by the FDA.24 The FDA imposes severe restrictions on manufacturers and distributors of pharmaceuticals regarding any promotion of an approved drug for any unapproved use. Thus, physicians must be careful to avoid placing themselves in situations in which their actions may be construed as, or they are in fact, "marketing" an off-label use of a drug.
A manufacturer is considered to "misbrand" a pharmaceutical if, inter alia, the drug's labeling includes information about unapproved uses.25 It is widely recognized that drug manufacturers often use indirect methods to promote off-label uses for their products. Congress is presently considering legislation to relax rules regarding the marketing of drugs for off-label indications.
Once the FDA has approved a prescription drug for a particular use or uses, the drug's manufacturer cannot market or promote the drug for an off-label use until it resubmits the drug for another series of clinical trials that are similar to those required for initial approval of a new drug application.26
Once off-label uses of a drug become a recognized use, federal regulations do impose a duty on the pharmaceutical company to issue appropriate warnings. In another case involving Cytotec (misoprostol), Moeltner v. G.D. Searle, et al, a patient was administered Cytotec, which is indicated for the treatment of gastric ulcers, off-label, to help "ripen" the cervix to assist in the induction of labor. Thereafter, a nurse administered Pitocin (oxytocin), allegedly contributing to uterine hyper-stimulation that resulted in severe fetal hypoxic encephalopathy. At trial, Searle, the pharmaceutical manufacturer, denied that it had a duty to provide warnings about off-label use of its drug by obstetricians and maintained that it never conducted testing on such uses. Plaintiff argued that although the use of Cytotec to facilitate uterine contractions was off-label, such use was recognized, the drug had been used in other countries as a "morning after pill," and 5-15 case reports in the medical literature substantiated the use of Cytotec in assisting the induction of labor. Plaintiff argued that the risk that Cytotec-induced uterine stimulation may have contributed to fetal anoxic brain injury also had been suggested in the medical literature. Plaintiff thus contended that once a drug company is aware that such off-label use was a recognized use and that literature exists regarding adverse incidents throughout the world, appropriate warnings should be issued. The pharmaceutical company settled sometime prior to trial for $2 million; the nurse and hospital settled shortly before trial for $3 million. The case then proceeded to trial against the Ob/GYN. The jury found the physician 67.4% negligent and the nurse 32.6% negligent. They rendered a gross award of more than $8 million, including more than $6.5 million on behalf of the child and more than $1 million to the mother for emotional distress. In sum, the settlements, the net verdict against the doctor of $5.5 million, and the prejudgment interest of $1.1 million, amounted to a total recovery of more than $11 million.
Future Liability. Finally, evolving State Medicaid Fraud Unit activities may represent an area of future liability exposure to physicians. FDA-approval for a specific medical indication represents a threshold issue, under most circumstances, in the determination by Centers for Medicare and Medicaid Services (CMS) as to whether the cost of that drug ("covered outpatient drug") will be reimbursed under the federal Medicaid program.28 In 1977, Congress enacted the Medicare-Medicaid Anti-Fraud and Abuse Amendments to Title XIX. These amendments authorized the creation of state Medicaid fraud control units and made funds available for states to prosecute Medicaid fraud.29 Medicaid fraud is modeled on the Federal False Claims Acts and is presently a high-profile enforcement initiative in almost every state. Most actions under the Medicaid False Claims Acts have been against manufacturers of pharmaceuticals for cases involving alleged promotion of off-label uses and kickbacks. This is an area of evolving law and physicians should proceed with caution when submitting claims for Medicaid payment for the administration of drugs, or manufacturer-subsidized rebates in circumstances of off-label drug use.
Additional Regulation of Physician Prescribing Practices
In the case of controlled substances, physicians may have significantly less discretion in off-label prescribing. Federal regulation of pharmaceutical controlled substances has a jurisdictional overlap between the FDA and the U.S. Drug Enforcement Administration (DEA), a division of the Department of Justice. Medications classified as "controlled substances" under the Controlled Substances Act (CSA)30 fall under the jurisdiction of the DEA. The CSA and the FDCA represent independent statutory schemes. Consistent with the role of the FDA in drug approval, the CSA does not specifically charge the DEA with a role in defining the appropriate medical uses for controlled substances. However, it is conceivable that Congress may condition or preempt FDA approval of an approved drug and require reclassification of a drug as a controlled substance in the interest of public safety.
The regulation of physician practice is traditionally within the scope of state power under the police powers delegated to the states by the U.S. Constitution. Thus, the individual states assume responsibility for licensing and discipline of physicians under state-specific statutes. The states confer prescriptive authority to licensed practitioners under state-specific statutory law. However, the statutory language in the FDCA and subsequent opinions and rulings is likely to generally preempt contradictory state laws regarding off-label prescribing by physicians.
The PDR as Evidence of the Standard of Care Regarding a Drug's Use
The Physicians' Desk Reference (PDR) is an annually published encyclopedia of medications, written and compiled by drug manufacturers, which taken together with the manufacturers' package inserts, is a vehicle for drug manufacturers to make physicians aware of possible side effects of various drugs.31
However, the PDR is by itself, widely held to be insufficient to establish the standard of care required of a defendant physician in a case of alleged malpractice.32
The question of whether the PDR in itself can be admitted as evidence of the standard of care has been litigated and contested. It is widely recognized at present that the PDR is not admissible regarding the standard of care concerning a physician's use of a medication.
Liability for Harm Caused by Approved Prescription Medications
Liability for injuries caused by manufactured products is generally governed by the concept of strict liability. "The doctrine of strict products liability renders the manufacturer of a defective product liable to any person injured thereby, regardless of privity, foreseeability or due care, if the defect was a substantial factor in bringing about the injury and provided (1) that at the time of the occurrence the product was being used for the purpose and in the manner normally intended, (2) that if the person injured is himself the user of the product he would not by the exercise of reasonable care have both discovered the defect and perceived its danger and (3) that by the exercise of reasonable care the person injured would not otherwise have averted the injury."33 "In the ordinary products liability case, the failure to warn follows a negligence formula ... 1) a duty on the part of the defendant to conform to a certain standard of conduct with respect to the plaintiff, 2) a failure by the defendant to so conform, and 3) a reasonably close causal connection between the defendant's conduct and some resulting injury to the plaintiff [proximate cause]."34 The rules of strict liability require a plaintiff to prove only that the defendant did not adequately warn of a particular risk that was known or knowable in light of the generally recognized and prevailing best scientific and medical knowledge available at the time of manufacture and distribution.35
However, courts have distinguished medical products from other manufactured goods based on the uncertainties relating to patients' individual responses to a drug or device; thus the "unavoidably dangerous" defense. The Restatement Second of Torts notes that:
There are some products which, in the present state of human knowledge, are quite incapable of being made safe for their intended and ordinary use. These are especially common in the field of drugs. An outstanding example is the vaccine for the Pasteur treatment of rabies, which not uncommonly leads to very serious and damaging consequences when it is injected. Since the disease itself invariably leads to a dreadful death, both the marketing and the use of the vaccine are fully justified, notwithstanding the unavoidable high degree of risk involved. Such a product, properly prepared, and accompanied by proper directions and warning, is not defective, nor is it unreasonably dangerous.36
Products that may be both properly designed and correctly manufactured may be considered to be dangerous and will be considered defective if not accompanied by proper warnings.
The Learned Intermediary Doctrine and Duty to Warn of Risk
The learned intermediary doctrine was first described in a 1966 case from the Eighth Circuit and has been subsequently widely adopted by the state courts. The learned intermediary doctrine is "the principle that a prescription-drug manufacturer fulfills its duty to warn of a drug's potentially harmful effects by informing the prescribing physician, rather than the end user, of those effects."37 The doctrine, in essence, states that each time a physician writes a prescription he or she stands as intermediary between his/her patients and drug manufacturers, thereby breaking a potential chain of a duty to warn. The doctrine focuses on the scope of a drug manufacturer's duty to warn of the dangers of the drugs that it markets. The duty of a manufacturer to warn of risks is fulfilled by providing adequate information and warning to the prescribing physicians who must subsequently balance the risks and benefits.38 The learned intermediary doctrine provides that manufacturers of prescription drugs have a duty to warn prescribing physicians of a drug's known dangerous propensities and that physicians, in turn, using their medical judgment, have a duty to convey the warnings to their patients. The doctrine precludes the imposition of a duty upon drug manufacturers to warn patients directly. The doctrine also has been applied to exempt pharmacies and pharmacists from giving warnings to patients.39 Generally, whether a warning is adequate is an issue of fact to be determined at trial; and, to constitute proximate cause, an inadequate warning must be a substantial cause of the events leading to the injury. Moreover, an act cannot be the "substantial cause" if the injury would have occurred regardless of the content of defendant's warning.40
In negligence cases, a plaintiff must demonstrate that the failure to adequately warn of the dangers of a drug was a proximate cause of the alleged injuries. A treating physician's decision not to inform a patient of the risk of injury represents an intervening cause, which then severs the causal connection between the patient's injury and the manufacturer, as would a physician's affirmative statement that he would have prescribed the drug even if adequately informed.41 At trial, during cases involving injuries caused by drugs or other products prescribed by physicians, the prescribing physician's knowledge of the risks of the item prescribed has precluded, as a matter of law, finding of proximate cause. Physicians' habit testimony that it is customary practice not to advise patients of certain risks, together with testimony to having knowledge of the risks, has been deemed to bar any finding of proximate cause.
The potential protection afforded by the learned intermediary doctrine is not absolute, as the case of Muss v. Goldstein suggests; a 43-year-old dentist sought treatment for emotional difficulties from defendant psychiatrist who diagnosed plaintiff with bipolar II disorder and prescribed Lamictal (lamotrigine). The use of Lamictal for bipolar II disorder was an off-label indication. Plaintiff developed Stevens-Johnson syndrome; this resulted in toxic epidermal necrolysis, a condition from which she died. The plaintiff's estate alleged that the physician misdiagnosed bipolar II disorder, that even if the patient did have bipolar II disorder, Lamictal was not a first-line treatment for the condition, that the defendant physician failed to obtain informed consent concerning the off-label use of Lamictal and specifically regarding the risk of hypersensitivity reaction that could progress to death and that other types of medications carried no such risks. The Fairfax County jury, who heard the case, awarded the patient's estate more than $3 million in damages after 1.5 days of deliberation, which was subsequently reduced in accordance with the state statutory cap on non-economic damages; this resulted in a final judgment of more than $1.6 million.42
Through progressive erosion of the traditional physician-patient relationship as a result of direct-to-consumer advertising, lifestyle medications, and physician-extenders, there is increased patient input regarding medication prescriptions. As a consequence, the legal justification for the learned intermediary doctrine are perceived to be weakening.
Conclusion: Physician Liability for Off-Label Prescription
The supplier of any product, including the manufacturer of pharmaceuticals, is under a duty to use "reasonable care" to "adequately warn" of the risks associated with the use of its product. However, the pharmaceutical manufacturer has no obligation to warn the ultimate user of danger propensities where there is an intermediary who is not a mere conduit of the product, but rather administers it on an individual basis.
Therein is a potential, but as yet apparently untested, vulnerability for physicians prescribing medications off-label: a potential assumption of duty (and risk) by the prescriber to warn the patient of the indeterminate risks associated with the prescription. In essence, it could be argued that when a physician prescribes a drug to a patient for an indication, at dose, or for a duration for which the drug has not been rigorously tested by the manufacturer, the physician might inadvertently "step into the shoes" of the manufacturer with respect to liability. Off-label uses have, by definition, not been tested by the manufacturer; therefore, drug interactions, adverse effects, and optimal dose and duration of therapy have not been defined. In such cases, the physician may be subject to liability for unforeseen effects, although such potential liability has not been litigated. Thus, even though off-label use is permissible, it is not without risk.
References
1. See generally, Federal Food, Drug, and Cosmetic Act as codified at 21 USC §§ 301-97 (2008). See also 21 USCS § 355 (2008), which sets forth the requirements for a New Drug Application to the FDA.
2. Szalados JE. Statutory and Regulatory Controls for Drug Development. In: Pharmaceutical Law: Regulation of Research, Development, and Marketing. Clark ME, ed. BNA Books, American Bar Association: Arlington, VA; 2007:1-120.
3. 21 CFR 312.1-312.70 and 312.110-312.145 (2008).
4. See 21 USCS § 355 (2008), 21 CFR 314.50 (2008).
5. See 21 USCS § 360e (2008), 21 CFR 314.50 (2008); note that the 'safe and efficacious' standard is found at 21 USC § 355(a),(b),(j) (2008).
6. Pub. L. No. 105-115, 111 Stat. 2296, (codified at various sections of 21 USC).
7. See 21 USC § 355(d) (2008).
8. See 21 USC § 321(k) & (m) (2008); see also 21 CFR § 202.1(1)(2) (2008).
9. 21 CFR § 201.5.10 (1990).
10. 21 USCS § 331 (2008). Specifically, § 331(k) states that "The alteration, mutilation, destruction, obliteration, or removal of the whole or any part of the labeling of, or the doing of any other act with respect to, a food, drug, device, or cosmetic, if such act is done while such article is held for sale (whether or not the first sale) after shipment in interstate commerce and results in such article being adulterated or misbranded."
11. See 21 CFR 807.87(e) (2008).
12. Washington Legal Found. v. Henney, 202 F.3d 331, 333 (D.C. Cir. 2000).
13. Buckman Co. v. Plaintiffs' Legal Comm., 121 S. Ct. 1012, 1018 (U.S. 2001).
14. 21 USCS § 396 (2008).
15. 59 Fed Reg 59820, 59821 (Nov. 18, 1994).
16. See, e.g., Rhone-Poulenc Rorer Pharm., Inc. v. Marion Merrell Dow, Inc., 93 F.3d 511, 514 n.3 (8th Cir. 1996); Bristol-Myers Squibb Co. v. Shalala, 91 F.3d 1493, 1496 (D.C. Cir. 1996); Ortho Pharm. Corp. v. Cosprophar, Inc., 32 F.3d 690, 692 (2d Cir. 1994).
17. United States v. Algon Chemical, Inc., 879 F.2d 1154, 1163 (3d Cir. 1989).
18. Zbras v. St. Vincent's Med. Ctr., 2003 Conn. Super. LEXIS 2217, 3-4 (Conn. Super. Ct. 2003).
19. 21 CFR 312.3.
20. Pirozzi v. Blue Cross-Blue Shield, 741 F. Supp. 586, 590 (D. Va. 1990).
21. Alvarez v. Smith, 714 So. 2d 652, 653 (Fla. 5th DCA 1998).
22. Id at 653-654.
23. Noah Betsinger, et al. vs. John Fontana, M.D., et al. U.S. District Court, District of South Carolina, Beaufort Division. Verdict Date: April 2003; Publication Date: May 2003. 2003 Jury Verdict Review Publications, Inc.
24. 21 USCS § 331 (2008).
25. This is consistent with and reaffirms the broad legal definition of "labeling" under the FDCA. See also 21 USCS § 352 (2008) defines 'Misbranded drugs and devices' to include, but not limited to a 'False or misleading label' (§ 352(a)); 'Prominence of information on label' (§ 352(c)); 'Directions for use and warnings on label' (§ 352(f)); 'Prescription drug advertisements' (§ 352 (n)). See also 59 Fed Reg 59820, 59821 (Nov. 18, 1994) (addressing misbranding of drugs and biologic products).
26. See 21 CFR §§ 314.54, 314.70, -.71 (2008).
27. Moeltner v. G.D. Searle, et al. New Jersey Jury Verdict Review & Analysis. Docket No. ESX-L-3981-02. Verdict Date: March 2007; Publication Date: June 2007. 2007 Jury Verdict Review Publications, Inc.
28. 42 USC § 1396b(i)(10)(2008). Note also that reimbursement requires that a covered drug "has been given a rating of 1-A by the Food and Drug Administration: 42 USCS § 1396r-8 (a)(3)(ii)(2008) and (k)(2)(A)(i) defining "covered drug" as "approved for safety and effectiveness as a prescription drug under section 505 or 507 of the Federal Food, Drug, and Cosmetic Act."
29. 42 USC §§ 1396b(a) - (q) (2008).
30. 21 USC §§ 801-904 (2008).
31. Spensieri v. Lasky, 94 N.Y.2d 231 (N.Y. 1999).
32. See e.g., Spensieri v. Lasky, 94 N.Y.2d 231 (N.Y. 1999) ("A physician's standard of care was established by the profession itself; expert's professional evaluation of defendants' conduct based, in part, on reliance on PDR contents was allowed, but PDR, by itself, could not establish the applicable standard of care for physicians who prescribe medications for their patients.")
33. Van Iderstine v. Lane Pipe Corporation, 89 A.D.2d 459, 455 N.Y.S.2d 450, 451-452 (N.Y. App. Div. 4th Dep't 1982) (citing Codling v. Paglia, 32 N.Y.2d 330, 342, 298 N.E.2d 622, 345 N.Y.S.2d 461 (N.Y. 1973)).
34. Tyler v. Kawaguchi Inc., 2006 U.S. Dist. LEXIS 12841, 9-10 (D.N.Y. 2006) citing Cresser v. American Tobacco Company, 174 Misc. 2d 1, 662 N.Y.S.2d 374, 379 (N.Y. Sup. Ct. 1997).
35. Carlin v. Superior Court, 13 Cal. 4th 1104 (Cal. 1996).
36. Restat 2d of Torts, § 402A (k). The American Law Institute 1965.
37. Black's Law Dictionary, 898 (7th ed., 1999).
38. See e.g., Sterling Drug, Inc. v. Cornish, 370 F.2d 82 (8th Cir. 1966) ("In a case involving a prescription drug rather than a normal consumer item, the purchaser's doctor is a learned intermediary between the purchaser and the manufacturer."); Wolfgruber v. Upjohn Co., 72 A.D.2d 59, 61 (N.Y. App. Div. 1979) ("the warnings are not found in the packaging of the drug, but are furnished instead to the medical community as the "informed intermediary" between the manufacturer and the patient ...").
39. Kasin v. Osco Drug, Inc., 312 Ill. App. 3d 823 (Ill. App. Ct. 2000).
40. Figueroa v. Boston Sci. Corp., 254 F. Supp. 2d 361, 370 (D.N.Y. 2003).
41. See Krasnopolsky at 1347.
42. Nicholas A. Muss, Executor Of The Estate Of Elizabeth L. Muss, Deceased v. Cynthia Goldstein Cohen, M.D. Circuit Court Fairfax County, VA. Case No. Withheld; Verdict Date: August 2005. JAS Publications: Metro Verdicts Monthly; 2005.
You are treating a patient that you feel would be a good candidate for 'Drug X.' Unfortunately, 'Drug X' is not indicated by the FDA for the treatment of that specific condition; and, you are unable to find prescribing information regarding the optimal dose or duration of therapy with 'Drug X' for that condition. You realize that your use of 'Drug X' in this circumstance would be considered "off-label." What legal risks, if any, might you face?You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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