### The HONORABLE DEAN WHIPPLE, United State s District Judge for 1 

### the Western District of Missouri. ___________ No. 95-3743

___________ Rhone-Poulenc Rorer * Pharmaceuticals, Inc., * * Plaintiff - Appellant, * * Appeal from the United States v. * District Court for the * Western District of Missouri. Marion Merrell Dow, Inc., * * Defendant - Appellee. *

___________ Submitted: April 10, 1996 Filed: August 22, 1996

___________ Before MAGILL, Circuit Judge, HENLEY, Senior Circuit Judge, and LOKEN , Circuit Judge.

___________ LOKEN, Circuit Judge.

This appeal challenges the district court's disposition of fals e 1 adve rtising claims by competing manufacturers of diltiazem, a "miracl e drug" for the treatme nt of hypertension and angina. The governing law is the false advertisingcause of action provided in § 43 of the Lanham Act, 15 U.S.C. § 1125(a)(1)(B). The court found both parties guilty of false advert ising. It awarded no damages to plaintiff Rhone-Poulenc Rore r Pharmaceuticals ("RPR") and ordered RPR to undertake corrective advertisin g to counter the effects of its Lanham Act violation. RPR appeals thos e rulings. We vacate as not sufficiently specific that portion of the decre e req uiring RPR to advise the marketplace of "the food effect" associate d with its product. We otherwise affirm.

### FDA will classify drugs as "bioequivalent" when their rat e 2 

### and ex tent of absorption by the body make them interchangeable

. Dru gs are bioequivalent when they have "the same strength an d similar bioavailability in the same dosage form." Bioavailability is "the degree to which a drug or other substance becomes av ailable to the target tissue after adm inistration." Dorland's Illustrated Medical Dictionary206 (27th ed. 1988).
-2- I. Background.

Defendant Marion Merrell Dow ("MMD") introduced the first diltiazem drug, Cardizem, in 1982. The FDA approved Cardizem for the treatment of angina; it was also widely prescribed to treat hypertension. In 1989, MMD int roduced a sustained release Cardizem product that is taken twice pe r day. MMD then developed Cardizem CD, a sustained release drug that i s taken only once per day. The FDA approved Cardizem CD for hypertension an d for angina.

Diltiazem was a pioneer new drug, which means that the Cardize m products enjoyed a te n-year period of market exclusivity under the HatchWaxman amendments to the Food, Drug, and Cosmetics Act. See 21 U.S.C

. § 355(j)(4)(D); Abbott Labs. v. Young , 920 F.2d 984 (D.C. Cir. 1990), cert
. denied , 502 U.S. 819 (1991). Cardizem products were immensely successful, gen erating sales of $1.1 billion in 1992 alone. By the early 1990's , competing drug manufacturers were anxious to penetrate the diltiazem marke t with less costly alternatives.

RPR la unched its diltiazem drug in June 1992. RPR's Dilacor XR, a
once -per-daysustained release tablet, initially received FDA new dru g approval for the treatment of hypertension but not angina. FDA approval
as a n ew drug, which is more rigorous than approval as a generi c substit ute, allowed Dilacor XR to compete with Cardizem CD during th e latter's period of market exclusivity. FDA classified Dilacor XR as a "BC" d rug -- one that is not necessarily "bioequivalent" -- rather tha n 2 a bioequivalent "AB" drug.

### -3-

Pharmacists may freely substitute among AB drugs, but only a prescribing physician may substitute one BC drug for another.

Given this FDA classification, to significantly penetrate th e diltiazem market RPR had to persuade physicians to prescribe its low-cost product, Dilacor XR, as a substitute for Cardizem CD. MMD of course wante d to persuade the same audience that this is an inappropriate substitution. With this issue as the battleground, the two companies launched advertisin g
ca mpaigns for the allegiance of doctors, pharmacists, and hospitals

. Becaus e these are sophisticated consumers, the battle was waged wit h te chnical advertisements in professional journals and with marketin g presen tations by each company's sales representatives. RPR sought t o convinc e prescribing physicians that Dilacor XR is the "same as, onl y cheaper" than Cardize m CD. MMD's message was, in essence, "not same as," and maybe not cheaper.

The natur e of the competing false advertising claims can be briefly summarized. MMD's defensive advertising began w ith literature telling its sales representatives that Dilacor XR might be only seventy-five percent
as bioavailable as Cardizem CD. After agreeing to discontinue tha t unsubstantiated claim, MMD's next wave of promotional materials advise d sales representatives, doctors, and pharmacists that studies showed Dilaco r XR only fifty percent as bioavailable as Cardizem CD. In its third wave of advertising, MMD r eleased a four-page brochure in April 1993 reporting the results of a comparative study conducted by an outside laboratory, the "6730 Study." The re sults, as reported by MMD: "Dilacor XR delivers 81% of a 180-mg dose relative to Cardizem CD" and "7 4% of a 540-mg dose." RPR
su ed, contending that these false comparative bioavailability claim s violate the Lanham Act.

Thro ughout this period, RPR's advertising urged doctors an d pharmacists to switch their patients from Cardizem products to the low-cos t Dilacor XR. In its counterclaims, MMD attacked this

### Doctors may prescribe an FDA-approved drug for non-approve d 3 

### uses, but the manufacturer may not promote non-approved uses.
-4- advert ising as falsely telling medical professionals that Dilacor XR i s freely substitutable for Cardizem products when in fact Dilacor XR is not FDA- approved for angina, physicians should monitor patients who switc h 3 from C ardizem CD because Dilacor XR does not have "simila r bioava ilability," and the two drugs are absorbed differently when take n with a meal (the "food effect").

After a bench trial, the district court found that MMD's earl y literature claiming that Dilacor XR has only sev enty-five percent or fifty percent bioavailability violated the Lanham Act. It enjoined MMD fro m making those claims. However, it found that MMD's advertising based upon the 6730 Study was not false, and it declined to award RPR money damages because RPR failed to prove damage resulting from MMD's earlier fals e advertising.
Turning t o MMD's counterclaims, the district court found that RPR's advertising "contain[ed] a hidden message encouraging indiscriminat e substitution" that is false in two respects -- Dilacor XR is not approved for treatment of angina, and Dilacor XR has a "food effect" that creates a risk of injury if physicians do not monitor pa tients who are switched to Dilacor XR. Based up on these violations, the court enjoined RPR to "take necessary steps" to advise sales representatives , physicians, pharmacists, and patients (1) of "the food effect associated with Dilacor XR," (2) that physicians should "carefully monitor and titrate" (adjust the dosages) whe n they switch patients from Cardizem CD to Dilacor XR, and (3) that "Dilacor XR is not approved to treat angina."
Following the district court's September 1994 decision, RPR filed a mot ion to correct the judgment, which the court denied. MMD moved t o enfo rce the court's order, and the court granted that motion withou t further explanation of what compliance is required.

### -5-

RPR appeals. It argu es that MMD was guilty of false advertising based on the 6730 Study, that the district court erred in denying RPR money damages , and that the court erred in ordering RPR to cond uct corrective advertising disclosing that Dilacor XR is not approved to tr eat angina and has a "food effect."
II. MMD's Advertising.

MMD advertised Dilacor XR's lower bioavailability in order t o persua de medical professionals that Dilacor XR is not a comparabl e substitute and to undercut Dilacor XR's price advantage. The tria l evid ence showed that MMD's first claim of seventy-five percen t bio availabilitywas false because it had no substantiation. The secon d claim of fifty percent bioavailability was false because it was based upon an obvious misinterpr etation of data from prior studies. But MMD's third cl aimof 74% to 81% bioavailability was based upon the speciall y commissioned 6730 Stu dy. The bona fides of that Study became a principal subject of the trial.
The Lanham Act prohibits "commercial advertising or promotion [that] misrepresents the nature, characteristics, quali ties, or geographic origin of [the advertiser's] or another person's goods, services, or commercial activities." 15 U.S.C. § 1125(a)(1)(B). False advertising decisions in other circuits have consistently distinguished between two types o f comparative advertising claims: "my product is better than yours," versus

" tes ts prove that my product is better than yours." To successfull y challenge the first t ype of claim, a Lanham Act plaintiff must prove that defendant's claim of superiority is false. But to successfully challenge th e second type of claim, where defendant has hyped the claim o f superi orityby attributing it to the results of scientific testing , pl aintiff must prove only "that the tests [relied upon] were no t sufficiently reliable to permit one to conclude with reasonable certainty that they established the proposition for which they were cited." Castrol , Inc. v. Quaker State Corp. , 977 F.2d 57, 62-63

### -6-

(2d Cir. 1992), quoting Procter & Gamble Co. v Chesebrough-Pond's, Inc. , 747 F.2d 114, 119 (2dCir. 1984). Accord BASF Corp. v. Old World Trading Co. , 41 F.3d 1081, 10 89-91 (7th Cir. 1994); Mylan Labs., Inc. v. Matkari , 7 F.3d 1130, 1138 (4th Cir. 1993), cert. denied , 114 S. Ct. 1307 (1994); McNeil-P.C.C., Inc. v. Bristol-Myers Squibb Co. , 938 F.2d 1544, 1549 (2d Cir. 1991). The district court applied this standard for "tests prove " claims to MMD's advertising based upon the 6730 Study. Neither part y challenges the standard, and we agree it is a correct application of Lanha m Act § 43.
RPR concedes that the 6730 Study res ults support the claims MMD made in its ad vertising brochure. Thus, the issue before us is whether tha t advertising was false because the 6730 Study is not a sufficiently reliabl e basis for comparing the bioavailability of Dilac or XR and Cardizem CD. At trial, RPR presented expert testimony that the 6730 Study was flawed i n design and execution, plus evidence that two RPR studies, the "113 Study" and th e "115 Study," did not have these flaws and refuted th e bioavailability concl usions of the 6730 Study. MMD countered with expert testim onysupporting the 6730 Study's methodology and attacking the RP R studie s. After weighing this conflicting evidence, the district cour t concl uded that the 6730 Study is a valid study "conducted by standard s accept ed within the scientific community and consistent with FD A principles."

On appe al, RPR concedes that the district court was free to rejec t RPR's evidence attacking the 6730 Study's methodology. But RPR argues tha t the results of its two studies refuted the 6730 Study, thereby proving tha t MMD's study did not s cientifically establish the inferior bioavailability of Dilacor XR. However, RPR's studies were not that conclusive. Th e single-dose 113 Study was more limited in scope and did not necessaril y refute MMD's claims. The 115 Study was not available when MMD bega n advertising the results of the 6730 Study, was criticized extensively by MMD's

### -7-

experts, and also sho wed a reduced bioavailability for Dilacor XR, albeit not as great as the difference found by the 6730 Study.

After carefully reviewing this evidence, we conclude the distric t court's finding that MMD did not falsely advertise the 6730 Study must be upheld. We do not have a "definite and firm con viction that a mistake has been made," the clear error standard in Anderson v. Bessemer City , 470 U.S

. 564 , 573 (1985). We note that Lanham Act liability for "tests prove " advertising requires proof that the tests are not "sufficiently reliable" to sup port the advertised conclusion with "reasonable certainty." T o
ensure vigorous competition and to protect legitimate commercial speech, courts applying this standard should give advertisers a fair amount o f leeway, at least in the absence of a clear intent to deceive or substantia l consumer confusion.

RPR also argues that it was entitled to money damages for MMD' s earlier false advertising. The Lanham Act provides that a successfu l plainti ff "shall be entitled" to recover "any damages sustained." 1 5 U.S.C. § 1117(a). Plaintiff must prove both actual damages and a causal link between defendan t's violation and those damages. See ALPO Petfoods, Inc
. v. Ralston Purina Co. , 913 F.2d 958, 968-69 (D.C. Cir. 1990)

. "[P]l aintiff may not recover if he fails to prove that the defendant' s actions caused the claimed harm." Harper House, Inc., v. Thomas Nelson, Inc. , 889 F.2d 197, 209 (9th Cir. 1989), quoting Otis Clapp & Sons, Inc. v. Filmore Vitamin Co. , 754 F.2d 738, 745 (7th Cir. 1985).
In this case, RPR did not attempt to prove that it incurred inc reased costs in countering MMD's false advertisements, one well-established metho d of pr oving Lanham Act damages. See ALPO , 913 F.2d at 969. Rather, RP R attem pted to prove that MMD's false advertising resulted in $40 to $5 6 million of lost Dilac or XR sales. However, the district court found that Dilacor XR sales "exc eeded [RPR's] initial predictions" and that "Dilacor XR is as

### -8-

well-po sitioned as should be reasonably expected at this stage in it s produc t history with or without [MMD's] anti-Dilacor campaigns." Thes e fin dings are not clearly erroneous and are directly responsive to RPR' s damage th eory. Thus, the district court did not abuse its remedia l discretio n in declining to award RPR damages. See Abbott Labs. v. Mea d Johnson & Co. , 971 F.2d 6, 16-19 (7th Cir. 1992) (standard of review)

. Likewise, because MMD discontinued its earlier false advertising and did not violate the Lanham Act in advertising the 6730 Study results, the cour t did not abuse its discretion in declining to order MMD to conduc t corrective advertising.
III. RPR's Advertising.

The distr ict court found that RPR's advertisements conveyed a false hidden message encouraging indiscriminate substitution of Dilacor XR for Cardizem CD. It ordered RPR to engage in correc tive advertising regarding the fact that Dilacor XR is not FDA-approved to treat angina, the need to monitor and titrate patients who switch from Cardizem CD to Dilacor XR, an d Dilacor XR's food effect. RPR concedes that its advertisements encouraged physicians to consider the two drugs freely subs titutable, and it does not appeal the order that it must effectively disclo se the need to monitor and titrate patients who switch drugs. But RPR does contend that the district court erred in orderi ng corrective advertising disclosing that Dilacor XR is not approved to treat angina and has a "food effect."

A. Rega rding the limited FDA approval issue, RPR notes that it ha s truthf ullyadvertised Dilacor XR as approved for the treatment o f hypertension. The di strict court erred, RPR argues, because a Lanham Act pla intiff alleging that advertising is false because it conveys a fals e implicit message must prove actual consumer confusion, and MMD presented
no such pr oof. See Johnson & Johnson * Merck Consumer Pharm. Co. v

. Smithkline Beecham Corp. , 960 F.2d

### Fu rthermore, MMD presented evidence of consumer confusion

. 4 

### One physician testified that an RPR representative told him tha t RPR's formulation of diltiazem "is the same as Cardizem CD." MMD prod uced affidavits from other physicians stating that they ha d been told by RPR representativ es that the drugs are the same. MMD also produced RPR physician surveys suggesting that consumer s viewed the two products as int erchangeable. Cf. PPX Enters., Inc. v. Audiofidelity Enters., Inc. , 818 F.2d 266, 271 (2d Cir. 1987).

-9- 294, 297-98 (2d Cir. 1992). We note that other Second Circuit cases have said that implicit falsity "should be tested by public reaction," not that a plaintiff such as M MD must prove confusion by consumer research. CocaCola Co. v. Tropicana Prods., Inc. , 690 F.2d 312 , 317 (2d Cir. 1982). But
we need no t resolve that issue because consumer confusion need not b e proved if advertising is literally false. 4

In assessing whether advertising is literally false, "a court mus t analyze the message c onveyed in full context." Castrol, Inc. v. Pennzoil Co. , 987 F.2d 939, 94 6 (3d Cir. 1993). Here, the record clearly supports the dis trict court's finding that RPR's advertisements were literall y false. The court focused on RPR advertisements featuring images such as two similar gasoline pumps or airline tickets with dramatically different prices, accompanied by the slogan, "Which one would you choose." The cour t fou nd that these ads falsely represented that the two drugs may b e indiscriminately subs tituted, in effect, a representation that Dilacor XR "has certain qualities that it in fact does not actually have." Abbo t Labs. , 971 F.2d at 14 . Because the implicit message was literally false, the i ssue became one of remedy -- what corrective advertising would b e appropriate. The district court determined that the false message would be remed ied if RPR adequately explained the differences in the tw o products, including the fact that Dilacor XR is not approved to trea t angina. There was no abuse of discretion in adopting that remedy. Se e First Bank v. First Bank Sys., Inc. , 84 F.3d 1040, 1044 (8th Cir. 1996)

### -10-

(standard of review); Pfizer, Inc. v. Miles, Inc. , 868 F. Supp. 437, 444 (D. Conn. 1994) (no false advertising when product differences ar e explained).

B. Tu rning to the food effect issue, we agree with RPR that one o f the district court's critical findings is clearly erroneous. The evidence , par ticularlyRPR's 113 Study, suggests that taking Dilacor XR with foo d will increase its ove rall extent of absorption by about nineteen percent, whereas taking Cardizem CD with food will decrease its overall extent of absorption by about t hirteen percent. The district court translated that evidence into the following finding: "within an hour of taking [Dilacor XR] after eating a high fat meal, a patient will experience a release of between 19% to 33% of the 24 hour dose." But the evidence addressed the overall, twenty-four hour extent of absorption, not the amount of product released during the f irst hour. Based upon this misinterpretation of the eviden ce, the court accused RPR of "callous indifference toward th e individuals ingestingits product" because "[a] patient with a weak heart who und ergoes this quick release of up to 33% of the total daily dosag e within an hour could experience serious health problems."
Although the court's finding of a quick release is not supported by the record, the evidence does support the general finding of a "foo d effect" because the bioavailability of Dilacor X R and Cardizem CD are more dissimilar if the pro ducts are taken during or after a meal. Indeed, FDA req uires that RPR packaging caution consumers that Dilacor XR should b e taken on an empty stomach. The issue then is how the district court' s
erroneous finding affects the validity of its order requiring RPR to advis e physicians, pharmacists, and patients of Dilacor XR's food effect.

Ru le 65(d) of the Federal Rules of Civil Procedure requires tha t "[e]veryorder granting an injunction . . . shall be specific in term s [and] shall describe in reasonable detail . . . the act or

### -11-

ac ts sought to be restrained." The Rule "is designed to preven t uncertaintyand confusion on the part of those to whom the injunction is directed, to avoid the possible founding of cont empt citations on an order that is t oo vague to be understood, and to ascertain that the appellat e court knows precisely what it is reviewing." Ca lvin Klein Cosmetics Corp.

v. Parfums de Coeur, Ltd. , 824 F.2d 665, 669 (8th Cir. 1987). Particularl y in light of the erroneous finding regarding the nature of Dilacor XR's foo d effect, we conclude that this portion of the per manent injunction violates Rul e 65(d) and must therefore be vacated. On remand, MMD may reques t additi onal injunctive relief regarding Dilacor XR's food effect, but i t should advise the district court what specific corrective advertisin g disclosures are requested and why such injunctiv e relief is necessary over and above the disclosures imposed upon RPR by the FDA.

We vacate one portion of the district court decree: "that Rhone

Po ulenc should take necessary steps to advise sales representatives , physicians, pharmacists and patients of . . . the food effect associated with Dilacor XR." In all other respects, the judgment of the distric t court is affirmed. RPR's motion to clarify the record on appeal is denied

.
A true copy.

Attest:

CLERK, U. S. COURT OF APPEALS, EIGHTH CIRCUIT.