The Drug Package Insert and the PDR as
Establishing the Standard of Care in
Prescription Drug Liability Cases

by Glenn E. Bradford¹ and Charles C. Elben²

Introduction

This article is the third in a series on the general subject of the medical standard of care under Missouri law. The initial article examined the general concept of standard of care under Missouri law, and specifically focused on the " respectable minority" doctrine as it has developed in courts in Missouri and around the country. ³ The second article took a closer look at Missouri's traditional requirement of "reasonable medical certainty" for expert medical testimony. ⁴ This article focuses on the evidentiary status in relation to the applicable standard of care of a prescription drug's labeling, package insert and the corresponding drug product information contained in the widely-available Physicians' Desk Reference (PDR), ⁵ "the standard reference work to which physicians turn when prescribing drugs." ⁶ Since we have found no reported Missouri appellate cases on point, ⁷ we survey the case law from other states on this issue and try to predict what a Missouri trial judge would do in similar circumstances.

In a prescription drug's labeling, package insert materials, and in parallel information printed in the PDR, ⁸ drug manufacturers provide guidance for the practicing physician as to how a given drug may be safely and effectively used. The Food and Drug Administration (FDA) requires drug manufacturers to provide package inserts to accompany prescription drug packages that describe the drug, outline its approved uses, recommended dosing and duration of use, summarize its possible beneficial and harmful effects on the patient, and give the physician directions for its use. ⁹ The insert is directed to the physician and is not customarily seen by the patient. ¹⁰ The manufacturer's package inserts are reprinted in the PDR, a copy of which is provided annually to all practicing physicians. ¹¹ A typical PDR entry for a given drug includes the trade and chemical names of the drug, a description of the drug, indications and contraindications for use, warnings about hazards from known drug interactions and other potential problems, overdosage, adverse reactions, administration and dosage, as well as information on managing and adjusting the dosage of the drug. ¹²

The issue addressed in this article is whether the drug manufacturer's directions for use, warnings, and cautions can be considered as setting the standard of care for a physician when prescribing that particular drug. In the alternative, if the drug manufacturer's guidance on the safe use of a drug is not conclusive as to the standard of care, what probative value, if any, would the manufacturer's labeling, package insert, or the corresponding PDR entry have as to the applicable standard of care? An even more fundamental question is whether the manufacturer's labeling, package insert, or the PDR entry is even admissible in evidence, either by itself or only when sponsored and referenced by an expert medical witness. In order to understand the issues, we must first take a look at the general law regulating the physician's use of prescription drugs.

Legal Limitations on Physician Prescribing

Medical negligence cases frequently involve issues related to the prescribing of therapeutic drugs. An example is a drug interaction case wherein the injured patient alleges that the physician (or pharmacist) has failed to take into account a known potential for a dangerous combination between two or more drugs. ¹³ Another example is a case involving alleged over-prescribing of a narcotic medication leading to personal injury or death. ¹⁴ An additional example might be a charge that a physician has failed to adequately monitor a patient's reaction to a course of drug therapy. ¹⁵ A further example is the "off-label" use case, in which the physician has prescribed a drug to treat a condition for which such use of the drug has not been specifically approved by the FDA as safe and effective. ¹⁶ Such an action would be based on the fact that "only FDA-approved uses" are permitted to be "listed in the indications section of the package insert or PDR entry." ¹⁷

The basic legal framework governing the development, production, distribution and marketing of drugs is contained in the Federal Food, Drug, and Cosmetic Act (FDCA) of 1938, as amended. ¹⁸ The act initiated the requirement that new drugs be tested and approved for safety and effectiveness for their stated uses by the FDA prior to being placed on the market. ¹⁹ As in other medical negligence cases, the initial inquiry in a case involving drug and pharmaceutical issues involves identifying the applicable standard of care. Drug manufacturers are required by the Food and Drug Administration (FDA) to issue guidance to pharmacists and physicians in the form of package inserts. ²⁰ These package inserts provide information for the physician about the drug in question, its properties, approved uses, appropriate dosages, possible drug interactions, and possible side effects. The manufacturer typically provides warnings as to any possible dangerous drug interactions and other known safety issues.

The question of the legal status of the PDR, labeling, and package insert instructions for use, warnings and cautions has been considered in a number of cases nationwide. ²¹ Physicians frequently take the position that the PDR, labeling, and package insert information constitutes informal guidance only. The argument is made by physicians that the Federal Food, Drug and Cosmetics Act permits the off label prescribing of drugs for purposes for which the FDA has not certified the drug as safe and effective. ²² Thus, the argument goes, the PDR and the package insert are not binding on the physician. ²³

Injured patients have often taken the position that the manufacturer of a drug is in the best position to evaluate when and how that particular drug should be used and that professional liability for injury should therefore follow when the disregarding of the manufacturer's advice by the physician leads to injury or death of the patient. ²⁴ Such cases have become increasingly popular and are known in the trade as "off-label" use claims. ²⁵

Physician "Freedom of Choice" in Prescribing

In general, the FDA has elected not to interfere with a physician's right to practice medicine according to his own rights and the dictates of state law, the FDA reasoning that only health care providers who are familiar with all aspects of a patient's unique and personal situation can properly determine the circumstances under which a given drug should be used. ²⁶ The right of a physician to prescribe for off-label uses has been referred to as a physician's "freedom of choice." ²⁷ "The use of approved drugs for indications not included in the labeling is permitted because a medical use may be fully appropriate even though it is not included within the labeling." ²⁸

In addition to permitting the use of a prescription drug for non-indicated purposes, compliance with the drug's labeling, package insert and the corresponding PDR information related to other phases of a drug's use is not made mandatory by the FDA, even though the FDA requires that the drug manufacturer provide guidance for the physician as to how to safely use the drug. ²⁹ Consistent with this general philosophy, it has been held that a consumer/patient does not have a private right of action against a pharmacist when harmed by what would otherwise constitute a violation of the FDCA. ³⁰

In the much cited ³¹ case of United States v. Evers, ³² the FDA attempted to restrain the prescribing of a physician who was using calcium disodium versenate to treat vascular diseases. The action was based on the fact that the drug's FDA-approved labeling did not approve this particular use for the drug, the labeling restricting approval for the drug's use only to the treatment of heavy metal poisoning. The defendant physician argued that the labeling did not specifically preclude his use of the drug to treat vascular diseases and that he had the right to use the drug according to his own best medical judgment. The court ultimately agreed with Dr. Evers and held that once a drug arrives in a local pharmacy, after interstate shipment, the physician may in the practice of medicine use the drug according to his or her best medical judgment without securing the approval of the FDA. ³³ The cases are essentially unanimous in reaching the conclusion that a licensed physician is entitled to use his or her best medical judgment regarding the appropriate, including off-label, use of FDA-approved prescription drugs. ³⁴

The director of the FDA Center for Drug Evaluation and Research has described off-label use as "[u]se for indication, dosage form, dose regimen, population or other use parameter not mentioned in the approved labeling." ³⁵ The FDA will generally allow a licensed physician to prescribe off-label without federal interference. However, the use of a drug in a way that is not specifically approved in the drug's official labeling may provide a basis for a common law tort claim against a health care provider, if the patient can establish that injury or death resulted from the failure of the physician or pharmacist to adhere to the uses suggested in the drug's official labeling. ³⁶

The Forward to the Physician's Desk Reference states in pertinent part as follows:

The FDA has also announced that the FD & C Act "does not, however, limit the manner in which a physician may use an approved drug. Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens or patient populations that are not included in approved labeling." Thus, the FDA states also that "accepted medical practice" often includes drug use that is not reflected in approved drug labeling.³⁷

The FDA cannot approve or disapprove of how a legally marketed drug is used by a physician in his practice. The agency approves of what a manufacturer may recommend about uses in its labeling (package insert) and advertising. Failure to recognize this distinction can have various harmful results.³⁸

Although the FDA does not police the use of FDA-approved drugs by physicians in their everyday practice, a physician might still have a liability for injuries resulting from the unapproved use of a drug under state negligence law principles. In prescription drug cases, there is no defense of federal preemption. ⁴² Therefore, state law controls. The FDA has taken the position that state tort liability is the "appropriate source of control for off-label uses" of prescription drugs. ⁴³ The FDA has also suggested that the off-label use of certain drugs has caused thousands of adverse reactions, including deformation, disability and death. ⁴⁴ However, the FDA has only attempted to exert control over the drug manufacturer's promotion of off-label use, ⁴⁵ and has not sought to otherwise interfere in the physician's practice of medicine. One commentator has stated that "tort suits for medical malpractice remain the only existing mechanism for regulating off-label use . . . ." ⁴⁶

Since the FDA and the courts have recognized that a practicing physician is not limited in her prescribing to the FDA-approved package insert information and may prescribe off-label without violation of federal drug laws and regulations, it would appear that it would be difficult for a court to hold that the package insert or the PDR establishes the standard of care per se. ⁴⁷ By announcing the position that state tort law is the appropriate control mechanism for the regulation of off-label prescribing, the FDA has in effect referred us back to the standard of negligence. The ultimate question for the finder of fact would seem to be whether or not the physician's admittedly off-label prescribing is non-negligent.

Development of the Standard of Medical Negligence

Generally, the standard of care for a physician is one established by the profession itself. ⁴⁸ The terms "negligent" or "negligence" as used in a Missouri medical negligence case are defined in the Missouri Approved Jury Instructions (MAI) as "the failure to use that degree of skill and learning ordinarily used under the same or similar circumstances by the members of the defendant's profession." ⁴⁹ This standard of care is usually described as that which physicians actually do in their everyday practice of medicine.

Determining the Standard of Care

Experts usually arrive at their opinions on standard of care by combining their own personal experience and knowledge of customary practices with their knowledge of the medical literature. ⁵⁰ Increasingly, specialty boards and government agencies are issuing standards of practice. ⁵¹ Practice guidelines have been defined as "systematically developed statements of recommendation for patient management to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances." ⁵²

The American Medical Association has recently endorsed the concept of clinical practice guidelines. In 1989, the AMA Office of Quality Assurance and Medical Review began publishing the Directory of Practice Parameters: Titles, Sources and Updates, ⁵³ which contains hundreds of practice guidelines in all fields of medicine. Many times the relevant standard can be found in a medical journal article or treatise. ⁵⁴ In many cases, the applicable standard of care is well known, unequivocal, and widely accepted in the medical profession.

When a prescription drug is involved in a death or personal injury, the drug package insert and the PDR is a logical place to begin when trying to determine the standard of care for the use of a particular drug. For example, in the lawyer's reference book Nursing Home Litigation: Investigation and Case Preparation, ⁵⁵ author Patricia W. Iyer advises lawyers in drug prescribing and monitoring cases as follows: "[p]rescribing guidelines for the elderly are contained in package inserts and the Physician's Desk Reference and are widely available in a number of other sources."

Physician Licensing Disciplinary Cases

As in civil medical negligence actions seeking money damages, professional licensing discipline cases frequently turn on standard of care issues. ⁵⁶ The Missouri State Board of Registration for the Healing Arts is set up by Chapter 334, RSMo, and is charged with licensing and disciplining the medical profession in the state of Missouri. ⁵⁷ The disciplinary portion of the healing arts practice law, § 334.100.2, RSMo 2000, does not specify quality of care standards in detail but regulates the quality of care indirectly by the incorporation of the concept of negligence (or violation of the standard of care) as one of the grounds for physician discipline by the Missouri State Board of Registration for the Healing Arts. For example, Chapter 334, RSMo 2000, provides that a physician's license may be disciplined for, among other things, "repeated negligence" ⁵⁸ or "gross negligence." ⁵⁹ Issues related to the prescribing of therapeutic drugs frequently appear in licensing disciplinary cases.

In addition to incorporating adherence to the applicable standards of care generally, the healing arts practice law ⁶⁰ also contains specific prohibitions related to the prescribing of drugs. Section 334.100.2(4)(h), RSMo 2000, provides that the board may take disciplinary action against the license of a physician for:

(h) Signing a blank prescription form; or dispensing prescribing, administering or otherwise distributing any drug, controlled substance or other treatment without sufficient examination, or for other than medically accepted therapeutic or experimental or investigative purposes duly authorized by a state or federal agency, or not in the course of professional practice or not in good faith to relieve pain and suffering, or not to cure an ailment, physical infirmity or disease, except as authorized in Section 334.104. (Emphasis supplied).

Therefore, a Missouri physician has two distinct types of liability for errors in the prescribing of drugs. The physician may incur common law tort liability for medical negligence and, in addition, the physician may encounter a licensing disciplinary action under the Missouri healing arts practice law brought by the state board. In both types of cases, the physician's prescribing will be judged primarily according to whether or not the physician has complied with the applicable standard of care.

Do the manufacturer's instructions for use, warnings and caution establish the standard of care?

Thus the question arises under Missouri law as to the evidentiary effect of the PDR or the package insert. Do the drug manufacturer's instructions for use, recommendations for monitoring, warnings and cautions as set out in the PDR and the package insert set, represent or reflect the applicable standard of care for a Missouri physician when prescribing drugs? Is the PDR or the package insert admissible in evidence in and of itself as proof of the truth asserted therein? If the PDR (or the package insert) is not admissible in and of itself as proof of the truth asserted on grounds of hearsay, is it admissible on the basis of notice to the defendant physician?

Does the package insert or the PDR set the standard of care for prescribing?

In the seminal case of Mulder v. Parke Davis & Co., the Minnesota Supreme Court was faced with an argument by a physician that the medical profession did not follow the dosage specified by the manufacturer in the package insert and so the recommended dosage did not represent the applicable standard of care. The court held that where the dosage is prescribed by the drug manufacturer, testimony concerning a physician's failure to adhere to the recommendation of the manufacturer is prima facie evidence of negligence sufficient to require the defendant physician to explain the reason for his deviation, particularly where manufacturer's warning puts the physician on notice of potentially lethal effects.

The Supreme Court of Minnesota enunciated the applicable "Mulder rule" as follows:

Where a drug manufacturer recommends to the medical profession (1) the conditions under which its drug should be prescribed; (2) the disorders it is designed to relieve; (3) the precautionary measures which should be observed; and (4) warns of the dangers which are inherent in its use, a doctor's deviation from such recommendations is prima facie evidence of negligence if there is competent medical testimony that his patient's injury or death resulted from the doctor's failure to adhere to the recommendations.⁶¹

The various states take three primary approaches to the PDR as evidence of the standard of care

Since Mulder was decided in 1970, the issue of the legal effect of the package insert or PDR has been considered by a number of state courts. ⁶⁴ With some overlap, three general interpretations give the package insert and PDR information varying degrees of authority as to the standard of care applicable in a medical negligence action. ⁶⁵ One approach allows the PDR, standing alone, to serve as the relevant standard of care. This line of cases holds that proof of a doctor's departure from the warnings contained in the PDR is sufficient evidence to establish a prima facie case of negligence. The majority of courts have adopted the moderate approach, allowing the PDR to be admitted into evidence as prima facie evidence of the appropriate standard of care, but holding that the PDR alone does not set the standard of care. The last group of holdings takes a reluctant approach to admitting the PDR into evidence. These courts hold that the PDR, without corroborating expert testimony, is hearsay and should be excluded.

The Package Insert and the PDR, Standing Alone, Establish the Standard of Care

Though not the majority, some courts have held that the PDR standing alone can establish the standard of care in a medical malpractice case. Foremost among these cases is Haught v. Maceluch, a Fifth Circuit case originating in Texas. ⁶⁶ On appeal in this case, the physician did not argue that the PDR was wrongly admitted as the standard of care. Rather, he contested that the PDR warnings did not apply to this particular case. When the court established that the PDR warnings did apply, they affirmed that the PDR was the appropriate standard of care and that the physician had breached that standard. ⁶⁷ Two recent Louisiana cases suggest the possibility that the Fifth Circuit's view is becoming more widely accepted. ⁶⁸ Both of these cases "considered the PDR sufficient evidence on its own to establish the standard of care." ⁶⁹

Mulder is distinguishable from Haught in that Mulder specifically states that a doctor deviating from the standard set by the PDR must justify the reasons for his deviation. ⁷⁰ Therefore, under certain circumstances a deviation from the PDR may be acceptable. Haught and a number of other similar holdings do not specifically address this issue.

The Package Insert and the PDR Constitute Some Useful Evidence Bearing on the Standard of Care

Most jurisdictions will not go so far as to allow the PDR to alone establish the standard of care in a medical negligence action. The majority at least allow the PDR to be admitted into evidence as some evidence of the standard of care. In Julien v. Barker, the Idaho Supreme Court held that the PDR "is not conclusive evidence of standard or accepted practice in the use of the drug by physicians and surgeons, nor that a departure from such directions is negligent. But it is prima facie proof of a proper method of use, given by the maker, which must be presumed qualified to give directions for its use and warnings of any danger inherent therein." ⁷¹

Other courts have extended the reasoning of the Idaho Supreme Court as set out in Julien, holding that a departure from the PDR is prima facie proof of negligence. ⁷² In Garvey v. O'Donoghue, the D.C. Court of Appeals adopted this approach, holding that . . . "in a medical malpractice case alleging improper administration, dosage, and monitoring of the drug, they (package insert and PDR information) are admissible both as prima facie evidence of the standard of care and physician's notice of their contents." ⁷³ Similarly, the South Dakota Supreme Court in Mueller v. Mueller held that "manufacturers' recommendations on the use of drugs are not only admissible but essential in determining the possible lack of care of a doctor where the issue involved is injury from the administration of a drug." ⁷⁴

The Supreme Court of Mississippi also adopted the reasoning of the Julien court, holding in Thompson v. Carter that the package insert is not conclusive evidence of a physician's standard of care but is prima facie proof of proper method of use. ⁷⁵ Echoing the Minnesota Supreme Court's Mulder opinion, the court added, "The holding will shift the burden of persuasion to the physician to provide a sound reason for his deviating from the directions for its use, and will require corroborative evidence to determine whether the physician met or violated the appropriate standard."

In Thompson v. Carter, the Mississippi Supreme Court held as follows:

This Court agrees that the package insert in the instant case should not be taken as conclusive evidence of the physician's standard of care, nor should a departure from the directions contained in the package insert be considered to establish a prima facie case of negligence. However, this Court holds the package insert contains prima facie proof of the proper method of use of (the drug) and, for those purposes, was admissible at trial. The package insert can be given weight as authoritative published compilation by a pharmaceutical manufacturer. It is some evidence of the standard of care, but it is not conclusive evidence. The prescribing physician can be permitted to rebut this implication and explain its deviation from the manufacturer's recommended use on dosage. The holding will shift the burden of persuasion to the physician to provide a sound reason for his deviating from the directions for its use, and will require corroborative evidence to determine whether the physician met or violated the appropriate standard.⁷⁶

A final line of cases manifests a reluctance toward allowing the PDR as evidence at all, often under the theory that scientific books and treatises when offered as proof of the facts asserted in them are excluded as hearsay. ⁷⁷ The largest sub-division in this group holds that PDR is admissible as evidence only when supported by expert testimony. ⁷⁸ This was the holding in Spensieri v. Lasky, where the New York Court of Appeals held that the PDR alone "constitutes hearsay and cannot, by itself, establish the applicable standard of care for physicians who prescribe medications for their patients." ⁷⁹ Accompanied by expert testimony, the PDR can be admitted as evidence. ⁸⁰ Looked at another way, these cases seem to hold that an expert may refer to the package insert and PDR information in the course of and as a part of his own expert testimony as to the applicable standard of care. In other words, the expert is allowed to point to the package insert and PDR information as supporting his own independent opinion as to the applicable standard of care. ⁸¹

In dicta, the Spensieri v. Lasky court sought to undergird this holding by offering policy reasons mitigating against allowing PDR entries, standing alone, to establish the applicable standard of care. The PDR is very general, the court noted, and is designed to cover a broad range of drugs and conditions. Therefore, it is ill-suited for establishing a standard specific enough for the particularized treatment of individual patients, observed the court. ⁸² "Moreover, [the court noted], the admission of the PDR alone, absent supporting expert testimony, would result in the standard of care being established by drug manufacturers instead of the medical profession and would prevent parties from being able to adequately cross-examine this type of evidence submitted on the key issue of standard of care." ⁸³ The court observed that, without explanatory expert testimony, the PDR would be difficult for a lay jury to understand and interpret. ⁸⁴

In Moore v. Director of Revenue, the Southern District of Missouri held in 1991 that the printed label on a drug container is hearsay but admissible nonetheless to prove the contents of the container. The ruling was considered to create a new exception to the hearsay rule in Missouri. The Southern District held that the factor of government regulation of drug packaging, along with the daily practice and experience based on a "circumstantial probability of trustworthiness." ⁸⁵

The Package Insert and PDR Entry as Notice–Hearsay Rule Not Implicated

In other cases it has been held that the package inserts and PDR entries are inadmissible as hearsay in determining the standard of care, but that this type of evidence can be used as proof that a doctor had notice of a particular danger associated with prescribing drugs under certain circumstances. ⁸⁶ In one such case originating in New Jersey, the court held that a package insert was admissible under the common-knowledge exception to the rule that expert testimony is needed in medical malpractice cases. ⁸⁷ In that case the accused dentist was aware of the warning in a package insert against prescribing a certain combination of drugs. The dentist ignored the warning and the patient died as a result of a lethal drug interaction. The court held that any person, not limited to a medical professional, on notice of such a potential danger, should take necessary precautions. ⁸⁸ In a number of other cases, the manufacturer's package insert and the parallel PDR reference was simply allowed to be considered by the jury, when supported by expert testimony, as one factor to be considered in determining the appropriate standard of care in a medical negligence case. ⁸⁹

PDR Information as Data Reasonably Relied on by the Medical Expert

It has been held that the package insert and PDR information are admissible as data reasonably relied on by a medical expert in forming his opinion.⁹⁰

In general, an expert may testify on the basis of data that is not itself admissible if the data is of a type reasonably relied upon by experts in the particular field in forming their opinions or inferences on the subject. It is clear, then, that the PDR and the package insert pertaining to Tobramycin may be used as a basis for expert testimony if the expert relied on them in forming an opinion. If, however, the evidence is proffered only as a basis for expert testimony, the document itself is not admissible.⁹¹

It would appear that Missouri law would allow a medical expert to rely upon the PDR reference for a given drug in forming his opinions and to so testify. In Callahan v. Cardinal Glennon Hosp., ⁹⁶ the Supreme Court of Missouri approvingly cited an expert's testimony based in part on the warnings for the drug in question from the package insert and the PDR. However, the Court did not discuss the issues related to the evidentiary effect of this evidence or the terms of its admissibility. It is widely known and an accepted fact that physicians customarily refer to the PDR in reference to the prescribing of prescription drugs. Even in the days before the passage of § 490.065, RSMo 2000, it had been held that an expert witness might make reference during testimony to publications not a part of the evidence of record, where the reference is made "to refresh his memory or to corroborate his own opinions." ⁹⁷

It has been held that the PDR cannot be characterized as a publication prepared for and relied upon by physicians and pharmacologists and, therefore, admissible as an exception to the hearsay rule under Federal Rules of Evidence 803(17) ⁹⁸ and comparable state rules of evidence. ⁹⁹ The court stated that "[t]ypically the publications covered by this exception to the hearsay rule are lists containing readily verifiable information such as telephone directories, price lists and the like. . . . In this instance of the PDR, interwoven among its factual statements are statements that correctly can be classified as directions, opinions, suggestions, and recommendations. Thus,it would be error to receive such evidence, on that basis, of the truth of the matters asserted therein." ¹⁰⁰

Missouri Administrative Hearing Commission Opinions on the Evidentiary Effect of the PDR

Although the Missouri judiciary has not spoken in any reported case about the legal effect of the PDR as evidence, the Missouri Administrative Hearing Commission (AHC) has rules on this question. ¹⁰¹ Although the opinions of the AHC are held not to be precedential, ¹⁰² it would seem that the AHC's reaction to the proffer of PDR evidence would be instructive and predictive of what a Missouri trial judge could be expected to do in a similar case.

In the case of Board of Registration for the Healing Arts v. Colom, ¹⁰³ the AHC considered the evidentiary effect of PDR entries in a case in which the board alleged various violations of the standard of care on the part of the respondent physician. After reviewing the various cases from around the country, the commission concluded as follows:

We agree that the PDR constitutes some evidence that the finder of fact may consider on the standard of care. The Foreword to the PDR states that a physician may prescribe medications contrary to the guidelines of the PDR and still adhere to acceptable standards of medical practice. The failure to follow the PDR is not per se, or even prima facie evidence of, a breach of the standard of care. However, the PDR is evidence that may be considered as to the standard of care.¹⁰⁴

Although [manufacturer's warnings] may provide useful information, they are not designed to establish a standard of medical practice, and their conflicting purposes make it extremely unlikely that they could be so designed.

* * *

[D]ifferences between the package insert and accepted medical practice represent the difference between the rigorous proof a regulatory agency must demand and the clinical judgment of a physician based on his [or her] training, experience, and skill as related to the needs of his [or her] individual patient. One cannot be taken as a standard for the other.¹⁰⁵

Conclusion

Although there appear to be no Missouri appellate cases directly on point, it has been held in a number of cases in other jurisdictions that the directions for use, warnings and cautions for a drug, as provided by the drug's manufacturer, represent the presumptive standard of care for the prescribing and use of that particular drug. ¹⁰⁷ "The great weight of authority is that a drug's labeling or its PDR reference is admissible, as long as it is accompanied by other expert evidence regarding the standard of care."¹⁰⁸

Most of the cases, whatever the theoretical underpinning, hold that proof of a variance by a prescribing physician from the manufacturer's instructions for use, recommendations for monitoring, warnings or cautions shift the burden of persuasion to the physician, requiring her to justify the departure from the manufacturer's guidance, at least in a practical if not formal sense of the term. Under all of the case law, proof of the PDR or package insert guidance is not considered to conclusively establish the applicable of standard of care and the prescribing physician always has the right to prove his reasoning for departing from the PDR or package insert. Of course, the presence or absence of documentation in the patient chart might have an impact on the persuasiveness of the physician's contentions.

Any way you look at it, the drug package insert and the parallel PDR references are highly useful in a case of therapeutic misadventure involving a prescription drug. Although no Missouri appellate case law has been found directly on point, cases from other states almost uniformly allow the admission into evidence of the drug manufacturer's guidance as provided to physicians in the package insert and the PDR. Although the various jurisdictions differ as to the precise evidentiary effect of admitting the package insert and PDR information into evidence, the ultimate practical effect would seem to be that a physician who fails to document compliance with the drug manufacturer's warnings, cautions, and directions for use would have the burden of persuasion, at least in the practical sense, to justify his prescribing to the jury.

Endnotes

¹ Glenn E. Bradford is a 1972 graduate of the Tulane University School of Law, where he was a member of the Board of Student Editors of the Tulane Law Review. Mr. Bradford practices as a trial lawyer in the firm of Glenn E. Bradford & Associates, P.C., in Kansas City, with emphasis on plaintiff's personal injury and criminal defense in state and federal court. Mr. Bradford has handled numerous medical negligence cases and has served as general attorney for the Missouri State Board of Registration for the Healing Arts since 1993, handling physician licensing disciplinary cases, many of which involve issues relating to the use and prescribing of prescription drugs.

² Charles C. Eblen is a second-year law student at Tulane University School of Law. He served as a law clerk for Glenn E. Bradford & Associates, P.C, during the summer, 2001.

³ Glenn E. Bradford, The "Respectable Minority" Doctrine in Missouri Medical Negligence Law, 56 J. Mo. Bar 326 (2000).

⁴ Glenn E. Bradford, Dissecting Missouri's Requirement of "Reasonable Medical Certainty," 57 J. Mo. Bar 136 (2001).

⁵ Hereafter sometimes referred to simply as "PDR" or "the PDR information" or the "PDR entry." When we refer to the PDR in this article, we are generally referring both to the information about a prescription drug contained in the drug's labeling and the package insert information, as approved by the federal Food and Drug Administration (FDA), and also the parallel information taken from the package inserts and reprinted in the Physician's Desk Reference or PDR, as it is widely known by professionals and laymen alike. In this context, the package insert information about a drug and its corresponding PDR entry are effectively the same thing. The publisher states that "Physician's Desk Reference is published . . . in cooperation with participating manufacturers. Each full-length entry provides you with an exact copy of the product's FDA-approved labeling." Physicians Desk Reference, 55th Ed., Medical Economics Company, 2001 (Foreword to the Fifty-Fifth Edition).

⁶ Kaspar J. Stoffelmayr, Products Liability and "Off-Label" Uses of Prescription Drugs, 63 U. Chi. L. Rev. 275, 276 (1996).

⁷ Although there are no cases on the evidentiary status of the package insert and/or the PDR in the reported cases from the state courts of appeal and the Supreme Court of Missouri, several cases have been decided by the Missouri Administrative Hearing Commission that consider the legal status of the package insert and/or the PDR as evidence impacting the standard of care. See, e.g., State Board of Registration for the Healing Arts v. George E. Colom, M.D., Case No. 94-000984 HA, before the Administrative Hearing Commission, State of Missouri (December, 1998). In this case, the commission notes that there appear to be no Missouri cases on this subject. The case of Campbell v. Preston, 379 S.W.2d 557 (Mo. 1964), involves a case in which a physician apparently ignored the manufacturer's warning as contained on the label of a drug. The Supreme Court of Missouri's opinion concerns the separate question of indemnity but obliquely confirms a jury verdict for the plaintiff. The Court's opinion contains no discussion of the issue of the effect of the manufacturer's warning.

⁸ Physicians Desk Reference, 55th Ed., Medical Economics Company, 2001 (Foreword to the Fifty-Fifth Edition).

⁹ For a detailed overview of the statutory and regulatory framework governing prescription drugs, see generally, Washington Legal Foundation v. Friedman, 13 F. Supp. 2d 51, 54-59 (D.D.C. 1998), amended, 36 F. Supp. 2d 418 (D.D.C. 1999), and appeal dismissed, judgment vacated in part by Washington Legal Foundation v. Henney, 202 F.3d 331, 340 (D.C. Cir. 2000).

¹⁰ The requirements for package inserts come from a number of statutes and regulations.

¹¹ Physicians Desk Reference, 55th Ed., Medical Economics Company, 2001 (Foreword to the Fifty-Fifth Edition). See, generally, Paul D. Rheingold & David B. Rheingold, Offense or Defense? Managing the Off-Label Use Claim, Trial, March 2001, at 52.

¹² Ramon v. Farr, 770 P.2d 131 (Utah 1989); See, e.g., Physicians Desk Reference, 55th Ed., Medical Economics Company, 2001, p. 3135 (entry for Thorazine®).

¹³ David B. Brushwood, Pharmacy Malpractice Law and Regulations, Aspen Law and Business § 8.6(2nd ed. 1998).

¹⁴ Cf., Cantrell v. State Bd. of Registration for the Healing Arts, S.W.2d ___ (2001).

¹⁵ See, e.g., State Bd. of Registration for the Healing Arts v. Eric Paul Fischer, D.O., Case No. 99-1508 HA, Missouri State Administrative Hearing Commission (Findings of Fact and Conclusions of Law, February 26, 2001) (http://www.oa.state.mo.us/ahc/page0005.html); see generally, David B. Brushwood, Pharmacy Malpractice Law and Regulations, Aspen Law and Business § 10.1 (2nd ed. 1998).

¹⁶ Paul D. Rheingold & David B. Rheingold, Offense or Defense? Managing the Off-Label Use Claim, Trial, March 2001, at 52, 53. It appears that the term "off-label use" is applied to any physician prescribing which involves an aspect not specifically authorized by the labeling, package insert or the PDR. Some would consider providing doses of a prescription medication greater than specified in the manufacturer's information as being "off-label" use.

¹⁷ Id.

¹⁸ 21 U.S.C. §§ 301, et seq. (2001).

¹⁹ David B. Brushwood, Pharmacy Malpractice Law and Regulations, Aspen Law and Business § 3.1 (2nd ed. 1998).

²⁰ In actual practice, the pharmacist typically purchases the drug and receives access to the package insert. A physician writing a prescription would not necessarily have access to the package insert for the drug ultimately dispensed at the pharmacy. However, physicians typically receive sample drugs from drug company salesmen and so have access to package inserts for the drugs they prescribe. In addition, drug manufacturers customarily provide physicians with product literature containing the information contained on the package inserts. The PDR also reprints the information contained in the package inserts. See, generally, David B. Brushwood, Pharmacy Malpractice Law and Regulations, Aspen Law and Business § 3.8 (2nd ed. 1998).

²¹ See generally, Linda A. Sharpe, Annotation, Malpractice: Physician's Liability for Injury or Death Resulting From Side Effects of Drugs Intentionally Administered to or Prescribed for Patient. 47 ALR5th 433, 466 (1997).

²² Paul D. Rheingold & David B. Rheingold, Offense or Defense? Managing the Off-Label Use Claim, Trial, March 2001, at 52, 55.

²³ Id.

²⁴ Id.

²⁵ Id.

²⁶ David B. Brushwood, Pharmacy Malpractice Law and Regulations, Aspen Law and Business § 3.8 (2nd ed. 1998).

²⁷ Dr. Alfred Soffer, Chest Editorials, "Chelation Clinics: An Abuse of the Physician's Freedom of Choice,"Chest (1984). The American College for Advancement in Medicine (ACAM) has issued a position paper discussing the concept of "freedom of choice" and the various legal theories supporting the concept. This paper may be found on ACAM's website at http://www.acam.org/chelationtherapyinformation.php. The article is also reprinted in "A Textbook on EDTA Chelation Therapy" Journal of Advancement in Medicine, Vol. 2, Nos. 1, 2, Spring/Summer, 1989, pp. 17-54. This combined issue is in print and copies are available through Human Sciences Press, Inc., 233 Spring Street, New York, NY 10013-1578. See, also, Sidney A. Shapiro, Limiting Physician Freedom to Prescribe a Drug for Any Purpose: The Need for FDA Regulation, 73 Nw.U. L. Rev. 801 (1978).

²⁸ David B. Brushwood, Pharmacy Malpractice Law and Regulations, Aspen Law and Business § 3.8 (2nd ed. 1998).

²⁹ See, generally, Lars Noah, Constraints on the Off-Label Uses of Prescription Drug Products, 16 J. Prod. & Toxics Liab. 139 (1994).

³⁰ Bailey v. Johnson, 48 F.3d 965 (6th Cir. 1995). Also holding that a violation of the FDCA does not create a private cause of action are: Pacific Trading Co. v. Wilson & Co., Inc., 547 F.2d 367, 370-71 (7th Cir. 1976); Griffin v. O'Neal, Jones & Feldman, Inc., 604 F. Supp. 717 (S.D. Ohio 1985); Keil v. Eli Lilly & Co., 490 F. Supp. 479, 480 (E.D. Mich. 1980); National Women's Health Network, Inc. v. A.H. Robbins Co., 545 F. Supp. 1177 (D. Mass. 1982); American Home Products Corp. v. Johnson & Johnson, 436 F. Supp. 785, 791 (S.D.N.Y. 1977), aff'd, 577 F.2d 160 (2nd Cir. 1978); Clairol, Inc. v. Suburban Cosmetics & Beauty Supply, Inc., 278 F. Supp. 859, 860-61 (N.D. Ill. 1968).

³¹ See, e.g., Richardson v. Miller, 44 S.W.3d 1 (Tenn. Ct. App. 2000).

³² 453 F. Supp. 1141 (N.D. Ala. 1978).

³³ See also, Rhone-Poulenc Rorer Pharm., Inc. v. Marion Merrell Dow, 93 F.3d 511, 514 n. 33 (8th Cir. 1996).

³⁴ See, e.g., Washington Legal Foundation v. Henney, 202 F.3d 331,333 (D.C. Cir. 2000); Chaney v. Heckler, 718 F.2d 1174 (D.C. Cir. 1983), rev'd, 470 U.S. 821 (1985).

³⁵ See Janet Woodcock, A Shift in the Regulatory Approach (Presentation to DIA Montreal June 23, 1997) (<http://www.fda.gov.cder/present/diamontreal/regappr/sld003.htm>) (visited July 5, 2000) (cited by the court in Richardson v. Miller, ___ S.W.3d ___, n. 3 (Tenn. Ct. App. 2000).

³⁶ See, e.g., Ramon v. Farr, 770 P. 2d 131 (Utah 1989). See, generally, David B. Brushwood, Pharmacy Malpractice Law and Regulations, Aspen Law and Business § 3.8 (2nd ed. 1998). See, Paul D. Rheingold & David B. Rheingold, Offense or Defense? Managing the Off-Label Use Claim, Trial, March 2001, at 52.

³⁷ Physicians Desk Reference, 55th Ed., Medical Economics Company, 2001 (Foreword to the Fifty-Fifth Edition).

³⁸ The FDA Does Not Approve Uses of Drugs, 252 JAMA 8, (1984).

³⁹ Paul D. Rheingold & David B. Rheingold, Offense or Defense? Managing the Off-Label Use Claim, Trial, March, 2001, at 52, 53.

⁴⁰ Richardson v. Miller, 44 S.W.3d 1, 14 (Tenn. Ct. App. 2001).

⁴¹ Kaspar J. Stoffelmayr, Products Liability and "Off-Label" Uses of Prescription Drugs, 63 U. Chi. L. Rev. 275, 278 (1996).

⁴² See, e.g, Pollard v. Ashby, 793 S.W.2d 394, 403 (Mo. App. E.D. 1990); Hurley v. Lederle Labs., Div. of Am. Cyanamid Co., 851 F.2d 1536 (5th Cir. 1988); Brochu v. Ortho Pharm. Corp., 642 F.2d 652 (1st Cir. 1981); See, generally, Patrick A. Malone, The Role of FDA Approval in Drug Cases, Trial, November 1998, at 28.

⁴³ 48 Fed. Reg. 26 733; Kaspar J. Stoffelmayr, Products Liability and "Off-Label" Uses of Prescription Drugs, 63 U. Chi. L. Rev. 275, n. 36 (1996) (citing 48 Fed Reg at 26733). See, generally, FDA, Legal Status of Approved Labeling for Prescription Drugs; Prescribing for Uses Unapproved by the Food and Drug Administration, 37 Fed Reg 16503 (1972); Use of Approved Drugs for Unlabeled Indications, 12 FDA Drug Bull 4, 5 (Apr. 1982).

⁴⁴ JAMA, July 3, 1991, Vol. 266, No. 1, FDA Scrutinizes "Off-Label" Promotions, Medical News and Perspectives, p. 11. See, also, Donald M. Payne, Consumers at Risk: Off-Label Use of Medical Drugs and Devices, Trial, August 1993, at 26.

⁴⁵ Id.

⁴⁶ William L. Christopher, Off-Label Drug Prescription: Filling the Regulatory Vacuum, 48 Food & Drug L. J. 247, 260 (1993).

⁴⁷ See, e.g., State Board of Registration for the Healing Arts v. George E. Colom, M.D., Case No. 94-000984 HA, before the Administrative Hearing Commission, State of Missouri (December, 1998) (Findings of Fact and Conclusions of Law, Section A, Manufacturer's Warnings, p. 52), where the Missouri State Administrative Hearing Commission ultimately reached this conclusion.

⁴⁸ See, generally, Spensieri v. Lasky, 723 N.E.2d 544 (N.Y. 1999).

⁴⁹ M.A.I. (5th ed.) 11.06 (Definitions–Negligence–Health Care Providers).

⁵⁰ Lori Rinella, The Use of Medical Practice Guidelines in Medical Malpractice Litigation–Should Practice Guidelines Define the Standard of Care?, 64 UMKC L. Rev., 337, 355 (1995).

⁵¹ See, e.g., Lori Rinella, The Use of Medical Practice Guidelines in Medical Malpractice Litigation–Should Practice Guidelines Define the Standard of Care?, 64 UMKC L. Rev., 337, 355 (1995); see, also, Oberman, "States Race to Whip up Practice Guidelines; Too Many Cooks?" Am. Med. News, Oct. 4, 1993, at 1.

⁵² Institute of Medicine. Clinical Practice Guidelines: Directions for a New Program. Washington, D.C.: National Academy Press; 1990.

⁵³ Office of Quality Assurance and Medical Review, American Medical Association. Directory of Practice Parameters: Titles, Sources, and Updates. Chicago, Illinois: American Medical Association; 1994.

⁵⁴ Id.

⁵⁵ Patricia W. Iyer, R.N., M.S.N., Nursing Home Litigation: Investigation and Case Preparation (1999, Lawyers & Judges Publishing Co., Inc.), page 91-92,

⁵⁶ An important distinction between civil medical negligence cases and professional licensing discipline cases is that it is generally not required that the state medical board establish that the questioned medical care caused injury. See Swope v. Printz, 468 S.W.2d 34, 39 (Mo. 1971) (plaintiff must show that defendant's negligent act or acts caused her resulting pain and suffering).

⁵⁷ The state's authority to regulate the medical profession is grounded in the Tenth Amendment to the United States Constitution. See, Dent v. West Virginia, 129 U.S. 114 (1889); Jacobson v. Massachusetts, 197 U.S. 11 (1905).

⁵⁸ In theory, a single instance of ordinary negligence is not a basis for discipline under the Healing Arts Practice Act. However, § 334.100.2(5), RSMo 2000, does provide that "repeated negligence" is a basis for disciplinary action. "Repeated negligence" is defined as 'the failure, on more than one occasion, to use that degree of skill and learning ordinarily used under the same or similar circumstances by the member [sic] of the applicant's or licensee's profession." Take out the term "repeated" and you have the M.A.I. definition of "negligence," as set out in M.A.I. 11.06. "The term 'negligent' or 'negligence' as used in this instruction means the failure to use that degree of skill and learning ordinarily used under the same or similar circumstances by the members of defendant's profession."

⁵⁹ Section 334.100.2(5), RSMo 2000. The Supreme Court of Missouri has held that, for the protection of the public health and welfare, "the [Missouri] legislature is empowered to regulate the practice of medicine in such [a manner as the Legislature deems] to be proper and wise." State ex rel. Collet v. Scopel, 316 S.W.2d 515 (Mo. 1958).

⁶⁰ Chapter 334, RSMo 2000.

⁶¹ 181 N.W. 2d 822 at 887 (Minn. 1970). To the same general effect are Ohligschlager v. Proctor Comty. Hosp., 303 N.E.2d 392 (Ill. 1973); Garvey v. O'Donoghue, 530 A.2d 1141 (D.C. 1987); Thompson v. Carter, 518 So.2d 609 (Miss. 1987); Hogle v. Hall, 916 P.2d 814 (Nev. 1996).

⁶² 181 N.W. 2d 822, at 887 (Minn. 1970).

⁶³ Harold L. Hirsch, The Medicolegal Implications of the Package Insert, Case & Comment, Jan.-Feb. 1977, at 14, 16, 18.

⁶⁴ In Lhotka v. Larson, 238 N.W.2d 870, 874 (Minn. 1976), the Minnesota Supreme court held that under Mulder no presumption of negligence exists unless the PDR contains a "clear and explicit" warning against the type of use that is alleged to have caused harm.

⁶⁵ The terms 'PDR,' 'package insert,' and 'manufacturers' instructions are used interchangeably and have been held by the courts to be synonymous.

⁶⁶ Haught v. Maceluch, 681 F.2d 291 n. 12, reh'g denied, 685 F.2d 1385 (5th Cir.1982).

⁶⁷ Id at 304.

⁶⁸ See generally, Fournet v. Roule-Graham, 783 So.2d 439 (La. Ct. App. 2001), and Terrebonne v. Floyd, 767 So.2d 758 (La. Ct. App. 2000).

⁶⁹ Fournet v. Roule-Graham, 783 So.2d 439 (La. Ct. App. 2001).

⁷⁰ Mulder, 181 N.W.2d 882, 887 (Minn. 1970).

⁷¹ Julien v. Barker, 272 P.2d 718, 724 (Idaho, 1954).

⁷² See generally, Salgo v. Leland Stanford Jr. Univ. Bd. of Trustees, 317 P. 2d 170 (Cal. Ct. App. 1957); Riffey v. Tonder, 375 A.2d 1138 (Md. App. 1977); Witherell v. Weimer, 499 N.E. 2d. 46 (Ill. App. 1986); Nolan v. Dillon, 276 A.2d 36 (Md. App. 1971).

⁷³ Garvey v. O'Donoghue, 530 A.2d 1141, 1146 (D.C. 1987).

⁷⁴ Mueller v. Mueller, 221 N.W.2d 39, 43 (S.D. 1974).

⁷⁵ Thomson v. Carter, 518 So.2d 609, 613 (Miss., 1987).

⁷⁶ Id.

⁷⁷ See Prince, Richardson on Evidence s7-313 [Farrell 11th ed.].

⁷⁸ See generally, Morlino v. Medical Ctr., 706 A.2d 721 (N.J. Super. App. Div. 1991); Ramon v. Farr, 770 P.2d 131 (Utah 1989); Craft v. Peebles, 893 P.2d 138 (Hawaii 1995)(PDR some evidence of standard of care, along with expert testimony).

⁷⁹ Spensieri v. Lasky, 723 N.E.2d 544 (N.Y. 1999).

⁸⁰ Id.

⁸¹ It has been held that an expert witness might make reference during testimony to publications not a part of the evidence of record, where the reference is made "to refresh his memory or to corroborate his own opinions." State v. Greenhaw, 553 S.W.2d 318, 326-27 (Mo. App. S.D. 1977). But see, Kelly v. St. Luke's Hospital, 826 S.W.2d 391, 396 (Mo. App. W.D. 1992) (a medical article held inadmissible hearsay during the direct examination of the plaintiff's medical expert witness. "Learned treatises, such as the article involved in this appeal, may be used during cross-examination to test or challenge an expert's testimony. However, the article is inadmissible hearsay during direct examination of appellant's expert witness.")

⁸² Sensieri v. Lasky, 723 N.E.2d 544 (N.Y. 1999).

⁸³ Id.

⁸⁴ Id.

⁸⁵ 811 S.W.2d 848, 852 (Mo. App. S.D. 1991).

⁸⁶ See, e.g., Koury v. Follo, 158 S.E.2d 548 (N.C. 1968); and Sanzari v Rosenfeld, 167 A.2d 625 (N.J. 1961).

⁸⁷ David C. Minneman, Annotation, Medical Malpractice: Drug Manufacturer's Package Insert Recommendations as Evidence of Standard of Care, 82 A.L.R. 4th 183 (1990) (citing Sanzari v. Rosenfeld, 167 A.2d 625 (N.J. 1961).

⁸⁸ Id.

⁸⁹ Morlino v. Medical Center of Ocean County, 706 A.2d 721 (N.J. Super. Ct. App. Div. 1998). See generally, Linda A. Sharp, Annotation, Malpractice: Physician's Liability for Injury or Death Resulting From Side Effects of Drugs Intentionally Administered or Prescribed for Patient, 47 ALR 5th 433, 466 (1997).

⁹⁰ Garvey v. O'Donoghue, 530 A.2d 1141 (D.C. 1987).

⁹¹ Garvey v. O'Donoghue, 530 A.2d 1141, 1144-45 (D.C. 1987).

⁹² See Missouri Evidence Restated, § 702, § 703 (MoBar 3rd ed. 1999 Supp.), for a comparison to the federal rules.

⁹³ Section 490.065.4, RSMo 2000 (effective in 1989).

⁹⁴ Section 490.065.3, RSMo 2000 (effective in 1989).

⁹⁵ See Missouri Evidence Restated, § 703 (MoBar 3rd ed. 1999 Supp.).

⁹⁶ 863 S.W.2d 852, 864 (Mo. banc 1993).

⁹⁷ State v. Greenhaw, 553 S.W.2d 318, 326-27 (Mo. App. S.D. 1977). But see, Kelly v. St. Luke's Hosp., 826 S.W.2d 391, 396 (Mo. App. W.D. 1992) (in a medical negligence action it was held not to be error for the trial judge to exclude the content of a medical journal article about cardiology procedures relied upon by an expert medical witness, over the contention that the article was admissible under § 490.065(3), and, if it was error, it was not prejudicial error since experts were permitted to testify to essentially the same thing).

⁹⁸ Fed. R. Evid. 803(17) provides that "[m]arket quotations, tabulations, lists, directories, or other published compilations, generally used and relied upon by the public or by persons in particular occupations" are not excluded by the hearsay rule.

⁹⁹ Missouri's rule is the same as the Fed. R. Evid. 803(17). See Missouri Evidence Restated, § 803 (MoBar 3rd ed. 1999 Supp.).

¹⁰⁰ Garvey v. O'Donoghue, 530 A.2d 1141, 1145 (D.C. 1987).

¹⁰¹ See, e.g., State Board of Registration for the Healing Arts v. George E. Colom, M.D., Case No. 94-000984 HA, before the Administrative Hearing Commission, State of Missouri (December, 1998)

¹⁰² Central Hardware Co. v. Director of Revenue, 887 S.W.2d 593, 596 (Mo. banc 1994).

¹⁰³ State Board of Registration for the Healing Arts v. George E. Colom, M.D., Case No. 94-000984 HA, before the Administrative Hearing Commission, State of Missouri (December, 1998)

¹⁰⁴ State Board of Registration for the Healing Arts v. George E. Colom, M.D., Case No. 94-000984 HA, before the Administrative Hearing Commission, State of Missouri (December, 1998) (Findings of Fact and Conclusions of Law, Section A, Manufacturer's Warnings, p. 52).

¹⁰⁵ State Bd. of Registration for the Healing Arts v. George E. Colom, M.D., Case No. 94-000984 HA, before the Administrative Hearing Commission, State of Missouri (December, 1998) (findings of Fact and Conclusions of Law, Section A, Manufacturer's Warnings, p. 51). Ramon v. Farr, 770 P.2d 131 (Utah 1989).

¹⁰⁶ State Board of Registration for the Healing Arts v. David F. Schlitt, M.D., Case No. 92-000918 HA, before the Administrative Hearing Commission, State of Missouri (October, 1993) (findings of Fact and Conclusions of Law).

¹⁰⁷ See, e.g., Mulder v. Parke Davis & Co., 181 N.W.2d 882 (Minn. 1970).

¹⁰⁸ Richardson v. Miller, 44 S.W.3d 1, 15 (Tenn. Ct. App. 2000).