Drug advertising and accountability.

At a time when pills are touted on TV and the Internet, the doctor's traditional role as a learned intermediary has been undermined. Pharmaceutical manufacturers should be held accountable for failing to warn consumers directly of the dangers posed by their products.

Anyone with a TV has seen the commercials: A former presidential-candidate-turned-spokesman for an erectile dysfunction drug, a gold-medalist skater touting a prescription pain medication, and the once-ubiquitous advertisements urging us to ask our doctor about a drug without revealing the condition it is supposed to treat.

Whether on television, radio, magazines, or billboards, pharmaceutical advertisements are unavoidable. The pharmaceutical industry spent an unprecedented $2.6 billion in direct-to-consumer (DTC) advertising in 2001. (1) This represents a spending increase of more than $200 million over the previous year. (2) Promotional spending directed at consumers increased by 212 percent between 1996 and 2000. (3)

DTC advertising of prescription drugs has been a source of controversy since it began in the early 1980s. The FDA announced a voluntary moratorium on the practice in 1982, perhaps prompted by concerns about an onslaught of advertisements for risky products consumers could not legally obtain without a prescription. (4) The agency said it needed time to study the issue before deciding whether such advertisements were proper.

In 1985, the FDA decided to allow DTC advertising. (5) DTC ads were required to meet the same disclosure requirements for risks and benefits as those directed at physicians. However, broadcast advertisements were exempted, as long as they contained a "major statement" of the risks and made "adequate provision" for consumers to obtain complete prescribing information. (6) Yet the FDA regulations did not define either requirement. The industry's uncertainty about what constituted "adequate provision" slowed the growth of broadcast DTC advertising, at least temporarily.

In response to industry concerns, the FDA released draft guidelines in 1997--finalized without substantial change in 1999--illustrating one approach to compliance. Under this approach, if broadcast material met the FDA's criteria for being "fair-balanced" and disclosed the most important risks, then "adequate provision" would be satisfied if the ad included each of the following: a toll free number through which complete prescribing information could be obtained, a reference to a print advertisement containing that information, disclosure of a Web page containing product information, and a referral to a health care provider. (7)

Arguably, the FDA's 1985 decision and the guidelines created a system in which consumers are exposed to diluted images of a product's true risks. By not requiring disclosure of all risks in advertisements, the system relies on the consumer to take the initiative to seek complete information. Having resolved the question of how "adequate provision" can be made, the agency set the stage for DTC advertising's rapid growth.

The prevalence of pharmaceutical advertising obscures the reason why these drugs are not available without a prescription. Indeed, as the New Jersey Supreme Court, quoting the Harvard Law Review, recognized in the landmark Perez v. Wyeth Laboratories, Inc.:

   "Research indicates that general warnings
   (for example, see your doctor) in [direct-to-consumer]
   advertisements do not give the
   consumer a sufficient understanding of the
   risks inherent in product use." Consumers
   often interpret such warnings as a "general
   reassurance" that their condition tan be
   treated, rather than as a requirement that
   "specific vigilance is needed to protect them
   from product risks." (8)

Trial lawyers, on the other hand, know all too well that prescription drugs and medical devices, despite their benefits, have the potential to cause great harm. The drug Thalidomide was responsible for horrific birth defects in an estimated 10,000 children in Europe. Women have suffered strokes from "the pill" and devastating complications from the Dalkon Shield and Cu-7 intrauterine devices (IUDs).

More recently, the diabetes drug Rezulin and the fen-phen diet drugs were withdrawn from the market due to life-threatening side effects. Currently, about 8,000 suits are pending over injuries and deaths linked to Baycol, a cholesterol-lowering medication withdrawn from the market in 2001. (9)

Unlike most products, prescription drugs and medical devices reach the consumer only through an intermediary: the physician. The physician, not the consumer, decides which product, if any, is appropriate. The physician traditionally does this through a risk-benefit analysis for each patient's unique situation and characteristics, and then informs the patient of potential side effects.

Recognizing the physician's role, the courts fashioned an exception--commonly known as the learned-intermediary rule--to the manufacturer's common law duty to warn consumers directly of reasonably foreseeable risks.

The rule originated in 1966 with Sterling Drug, Inc. v. Cornish, in which the Eighth Circuit explained the doctor's unique role:

   [I]n this case, we are dealing with a prescription
   drug rather than a normal consumer
   item. In such a case, the purchaser's doctor is
   a learned intermediary between the purchaser
   and the manufacturer. If the doctor is properly
   warned of the possibility of a side effect in some
   patients, and is advised of the symptoms normally
   accompanying the side effect, there is an
   excellent chance that injury to the patient can
   be avoided. (10)

Simply put, the learned-intermediary rule provides that a prescription drug manufacturer fulfills its obligation to warn of foreseeable risks by providing these warnings to physicians. If the prescribing physician has received adequate notice of possible complications, the manufacturer has no duty to warn the consumer directly. (11) The rationale for the rule is that the physician, not the patient, is in the best position to minimize the risks.

The learned-intermediary rule is a trap for the unwary. Litigants can confront it head-on by showing that the warnings given to the physician were inadequate, or sidestep it through an exception. Understanding the rule and its exceptions can help you avoid its pitfalls and perhaps turn the tables on the defendant.

Generally, courts have based the application of the learned-intermediary rule on the following factors:

* the existence of a physician-patient relationship 

* a desire not to interfere with that relationship

* the presumed inability of drug makers to communicate directly with patients

* the complexity of the subject

* the physician's specialized education and training and individualized medical judgment.

When these justifications are absent, courts have found the learned-intermediary rule inapplicable and have required direct warnings to consumers. Although the exceptions have only limited recognition, an understanding of their common rationale is important anytime you must overcome the learned-intermediary rule. Some courts have declined to apply the rule in cases involving:

* vaccines administered in mass-immunization clinics

* oral contraceptives and contraceptive devices 

* overpromoted drugs

* drugs withdrawn from the market

* drugs that are advertised directly to consumers. (12)

Vaccines

The first exception was created in cases involving the Sabin oral polio vaccine--which, like many vaccines, had the potential to cause the very disease that it was intended to prevent. Davis v. Wyeth Laboratories, Inc., is typical. (13)

In Davis, the vaccine was given in a clinic setting by a pharmacist instead of a physician. Everyone who showed up received the vaccine as part of a mass-immunization program. The plaintiff did not get the benefit of a physician's individualized medical judgment, nor was he informed that a potentially safer alternative existed. The Ninth Circuit refused to apply the learned-intermediary rule, recognizing that traditional justifications for it were absent.

The Second Circuit reached a different result in Plummer v. Lederle Laboratories, another case involving the Sabin polio vaccine. (14) In Plummer, a physician prescribed and administered the vaccine himself. He testified that he was aware of the vaccine's dangers but did not warn patients because he believed that the risks were slight compared to the benefits. Since the physician made an individualized medical judgment, the court did not apply the exception. The Fourth Circuit later reached the same result in a case involving a flu vaccine prescribed and administered by a physician. (15)

These vaccine cases illustrate the significance that courts place on the interaction between patient and physician. In any pharmaceutical or medical device case, thoroughly explore the substance of that interaction. The questions to be answered include the following:

* Was the plaintiff actually seen by a physician?

* Did the physician make an individualized medical determination that the drug or vaccine was right for the plaintiff?

* What was the risk of side effects for this particular plaintiff?

* Were other, potentially safer, alternatives available?

If there was a breakdown in the physician-patient interaction, you'll need to determine whether it was reasonably foreseeable by the manufacturer.

Also, learn whether the physician relied on warnings provided by the manufacturer. The prescribing physician's testimony has the potential to establish or defeat proximate causation. When a doctor did not even read the manufacturer's warnings, or had independent knowledge of the risks, some courts have held that the manufacturer cannot be held liable even if its warning was inadequate. (16)

Contraceptives

The physician-patient interaction is also a recurring theme in cases involving oral contraceptives. For example, in MacDonald v. Ortho Pharmaceutical Corp., the Massachusetts Supreme Judicial Court held that manufacturers of these drugs must warn patients directly of product risks. (17) The court's decision rested on the following considerations:

* Oral contraceptives are generally taken by young, healthy women.

* Multiple forms of contraceptives are available, and the decision to use the pill is typically made by the patient.

* Gynecologists generally prescribe the pill after seeing the patient only once and will often not see her again for another year.

* FDA regulations require that written information be supplied to users of oral contraceptives.

The Eighth Circuit also considered DTC advertising of contraceptive devices in Hill v. Searle Laboratories. (18) The plaintiff alleged injuries caused by the Cu-7 IUD. Although doctors involved in Hill's treatment believed the warnings to be adequate, the court held that warnings to a learned intermediary did not satisfy the defendant's duty to warn.

In addition to the factors recognized in the oral contraceptives cases, the court noted that Searle marketed the Cu-7 directly to consumers for the purpose of influencing women to choose it. The court found that "IUD manufacturers, through mass advertising and merchandising practices, generated a general sense of product quality, making it difficult for consumers to fully understand the risks involved with the use of an IUD." (19)

Like the vaccine cases, those involving contraceptives turn on the nature of the physician-patient interaction. As in the vaccine cases, courts that have followed the contraceptives exception have based their rulings on a departure from the physician's traditional role in prescribing medication.

The contraceptives cases suggest that in evaluating a pharmaceutical case, you must determine the patient's role in choosing a particular treatment, the extent of physician follow-up that can be expected, and the frequency and severity of side effects. The manufacturer of a drug with serious side effects should not be allowed to escape liability if it is reasonably foreseeable that patients will have little, if any, follow-up with the prescribing physician. Under such circumstances, the physician is not in a position to reduce the risk of harm.

Overpromotion

Even if physicians are adequately warned by product labels, liability may still be imposed on a pharmaceutical manufacturer, using a theory of overpromotion. The North Carolina Court of Appeals recognized that a manufacturer should not be absolved of liability if aggressive marketing leads the medical community to overlook a drug's dangers despite warnings. (20)

In another case, the Fourth Circuit held that even when a product label contained adequate warnings, a jury could decide whether advertising material--in this case, a calendar for a physician's desk--that lacked product warnings was sufficient evidence of overpromotion to nullify the warning on the label. (21)

When alleging overpromotion in pharmaceutical cases, your two most important depositions will probably be the prescribing doctor and the "detail person." The detail person is the manufacturer's representative who promotes drugs to physicians and gives them prescribing information.

When deposing the detail person, find out what he or she was told about the severity and frequency of side effects, the warning signs or symptoms associated with them, and contraindications for taking the medication. Through discovery or subpoena, get all the product information that the detail person gave the prescribing physician.

In the doctor's deposition, ask what the detail person said about product risks, what promotional material he or she gave the doctor, and whether that information provided the doctor with an accurate picture of the product's true risks. If discovery produces documents showing a greater incidence of side effects than that conveyed in the warnings or promotional material, ask the physician whether that information would have altered his or her risk-benefit analysis and the ultimate decision to prescribe the drug to your client.

One source of data on the frequency of side effects is adverse event reports, which all drug manufacturers maintain and are required to submit to the FDA periodically. Although they generally are not considered scientifically reliable causation evidence under Daubert v. Merrell Dow Pharmaceuticals, Inc., (22) and will probably face hearsay objections, the reports should be admissible for the purpose of showing that the manufacturer had notice of its products' reported side effects.

Drugs withdrawn from the market

Unfortunately, the exception for drugs withdrawn from the market is not as broad as its name implies. It is narrow and fact-dependent, as illustrated in Nichols v. McNeilab, Inc. The case involved Zomax, a drug intended to be used as needed for menstrual pain. (23) Consequently, it was not unusual for a bottle to remain in the patient's medicine cabinet long after she filled the prescription. Zomax caused allergic reactions that were sometimes fatal. The manufacturer announced its withdrawal through press releases and letters to physicians. In Nichols, the patient's estate alleged she suffered a fatal allergic reaction to Zomax about a year after it was removed from the market.

The Nichols court drew a distinction between warnings to a doctor before a drug is prescribed and warnings that accompany a drug's removal from the market. The court emphasized that Zomax was intended to be taken intermittently and reasoned that if warnings to physicians were sufficient to discharge the duty to warn, then doctors would be left to shoulder the burden of notifying all patients to whom they had prescribed the drug. Given the logistical difficulties of doing so, the court said, it was foreseeable that warnings would not reach all users of the product. Concluding that the manufacturer was at least as capable as the prescriber of effectively providing notice to the consumer, the court thus allowed the jury to decide whether the press release and letter to physicians were sufficient to satisfy the duty to warn.

Drugs advertised to consumers

The New Jersey Supreme Court created the most recent exception to the learned-intermediary rule in Perez. The court held that "when mass marketing seeks to influence a patient's choice of a drug, a pharmaceutical manufacturer that makes direct claims to consumers for the efficacy of its product should hot be unqualifiedly relieved of a duty to provide proper warnings of the dangers or side effects of the product." (24)

The product at issue was the Norplant contraceptive, which comes in the form of capsules that are implanted under the skin of a woman's arm. The plaintiffs alleged that the manufacturer failed to warn of the pain and scarring associated with removing the capsules. They claimed that Wyeth aggressively marketed the product to consumers instead of physicians, and that none of the magazine or television advertisements warned of Norplant's risks, but instead emphasized its convenience and simplicity.

In its analysis, the court noted the growth of DTC pharmaceutical advertising and underscored how the practice has changed the physician-patient relationship. The court became the first to recognize an exception to the learned-intermediary rule for DTC advertising, determining that it undermines traditional justifications supporting the rule.

The victory for plaintiffs was not unqualified, however. The court stated that when DTC advertisements comply with FDA requirements for disclosure of risks and efficacy, a rebuttable presumption arises that the manufacturer has met its duty to warn. In this court's opinion, "compliance with FDA standards should be virtually dispositive of such claims." (25)

This portion of the decision is troublesome. Unlike product labels and promotional material given to health care providers, FDA regulations regarding DTC marketing do not, in most cases, require the agency's review before publication or broadcast. (26) The regulations provide only that such advertisements may be submitted to the FDA for comment. Moreover, the rebuttable presumption is likely to inject and perhaps lend credibility to the pharmaceutical defendant's favorite issue: federal preemption.

Plaintiffs in other jurisdictions may avoid this presumption because its source is a New Jersey statute. (27) The stature provides that when a manufacturer's warning has been approved by the FDA, it is presumed to be adequate. Perez simply applied this statute to warnings contained in the DTC advertisements at issue. Consequently, plaintiffs in states that do not have similar statutes can use the ruling's exception for DTC advertising while distinguishing the portion that addresses the rebuttable presumption.

Creating demand

Today's patients have access to information as never before. The Internet gives instant access to prescription drug information previously restricted to the medical profession. Publications such as the Physician's Desk Reference and numerous other medical references are sold directly to the public. Surely, this unparalleled access to information has contributed to the steady decline of the "doctor knows best" mentality.

Patients are much more likely than ever to ask a doctor to prescribe a particular medication--often without a full appreciation of the hazards. A recent FDA survey showed that a majority of physicians believed patients had unrealistic expectations about the effectiveness of prescription drugs and little, if any, understanding about their possible risks and negative effects. (28)

The phenomenon of online pharmacies illustrates the demand created by DTC marketing. A revealing exercise is to conduct a simple Internet search for the name of a prescription drug advertised on television. Numerous sites will appear. While some legitimate online pharmacies offer only prescription refills, many offer to write a prescription for the drug of the customer's choice, fill it, and ship it by express delivery. They claim to employ physicians who make prescribing decisions based on a simple online questionnaire. Astonishingly, the doctors do so without reviewing--or even having access to--medical records, without a face-to-face meeting, without a physical exam, and without any follow up.

These sites exist only because their products are in demand. The demand exists, in large part, because pharmaceutical manufacturers set out to create it.

DTC advertising of prescription drugs is here to stay, and for now, so is the learned-intermediary rule. Yet the pharmaceutical industry's attempts to influence the physician-patient relationship are paving the way for the rule's demise. The New Jersey Supreme Court has taken an important first step with its Perez decision. The question is, how will courts in other jurisdictions respond?

Plaintiff lawyers can shape the answer. Consider the learned-intermediary rule and its exceptions in screening cases, drafting your complaint, requesting discovery, and compiling your evidence for trial.

Notes

(1.) IMS Health, Total U.S. Promotional Spending by Type, 2001, available at www.imshealth. com/ims/portal/front/articleC/0,2777,6599_9285_ 1004963,00.html (last visited May 5, 2003).

(2.) IMS Health, Total U.S. Promotional Spending by Type, 2000, available at www.imshealth. com/ims/portal/front/articleC/0,2777,6599_40054629_ 1004827,00.html (last visited May 5, 2003).

(3.) Meredith B. Rosenthal et al., Promotion of Prescription Drugs to Consumers, 346 NEW ENG. J. MED. 498 (2002).

(4.) Wayne L. Pines, A History and Perspective on Direct-to-Consumer Promotion, 54 FOOD & DRUG L. J. 489, 492 (1999).

(5.) Id. at 493.

(6.) Id.

(7.) Ctr. for Drug Evaluation & Research, U.S. Food & Drug Admin., Guidance for Industry: Consumer-Directed Broadcast Advertisements (Aug. 1999), available at www.fda.gov/cder/guidance/ 1804fnl.htm (last visited May 5, 2003).

(8.) 734 A.2d 1245, 1253 (N.J. 1999) (citing Jon D. Hanson & Douglas A. Kysar, Taking Behavioralism Seriously: Some Evidence of Market Manipulation, 112 HARV. L. REV. 1420, 1456 (1999)).

(9.) Jim Hopkins, Stakes Huge in Baycol Lawsuit, USA TODAY, Mar. 11, 2003, available at www.usatoday. com/money/industries/health/drugs/2003-03-11-baycol_ x.htm (last visited May 16, 2003);Attorneys Press Discovery Effort in Litigation over Cholesterol Drug, TRIAL, June 2003, at 12.

(10.) 370 F.2d 82, 85 (8th Cir. 1966); see also RESTATEMENT (SECOND) of TORTS [section] 402A, cmt. k (1965).

(11.) Brooks v. Medtronic, Inc., 750 F.2d 1227 (4th Cir. 1984).

(12) Vitanzia v. Upjohn Co., 778 A.2d 829, 846-47 (Conn. 2001).

(13) 399 F.2d 121 (9th Cir. 1968); sec also Reyes v. Wyeth Labs., 298 F.2d 1264 (5th Cir. 1974).

(14.) 819 E2d 349 (2d Cir. 1987).

(15.) Stanback v. Parke, Davis & Co., 657 F.2d 642 (4th Cir. 1981).

(16.) Id. at 645-47. See also Kirsch v. Picker Int'l, Inc., 753 F.2d 670, 671-73 (8th Cir. 1985); Odom v. G.D. Searle, 979 F.2d 1001, 1003-04 (4th Cir. 1992). But see Reyes, 298 F.2d 1264, 1281 (holding that there is a rebuttable presumption that the consumer would have read any warning provided by the manufacturer and acted to minimize the risks).

(17.) 475 N.E.2d 65 (Mass. 1985).

(18.) 884 F.2d 1064 (8th Cir. 1989).

(19.) Id. at 1070.

(20.) Whitley v. Cubberly, 210 S.E.2d 289 (N.C. Ct. App. 1974). See also Proctor v. Davis, 682 N.E.2d 1203 (Ill. App. Ct. 1997); Holley v. Burroughs Wellcome Co., 348 S.E.2d 772 (N.C. 1986).

(21.) Salmon v. Parke, Davis & Ch., 520 F.2d 1359 (4th Cir. 1975).

(22.) 509 U.S. 579 (1993).

(23.) 850 F. Supp. 562 (E.D. Mich. 1993).

(24.) Perez, 734 A.2d 1245, 1247.

(25.) Id. at 1259.

(26.) 21 C.F.R. [section] 202.1(j)(4) (2002).

(27.) N.J. STAT. ANN. [section] 2A:58C-4 (West 2002).

(28.) Kathryn J. Aiken, Direct-to-Consumer Advertising of Prescription Drugs: Physician Survey Preliminary Results (Jan. 13, 2003), available at www.fda.gov/cder/ddmac/globalsummit2003 (last visited May 16, 2003).

Gerald D. Jowers Jr. practices law with Suggs & Kelly Lawyers in Columbia, South Carolina.