BERYL A. HOWELL, District Judge.
Dietary supplement designers and industry groups brought this lawsuit challenging a decision of the Food and Drug Administration ("FDA") to deny a petition for authorization of certain qualified health claims regarding dietary supplements containing vitamin C and vitamin E. The plaintiffs assert the FDA's decision has violated their First Amendment rights. Invoking both circuit and district court opinions that have addressed similar claims, plaintiffs seek a declaratory judgment that the FDA's final order denying the petition is invalid and a permanent injunction enjoining the FDA from "taking any action that would preclude the Plaintiffs from placing [their proposed] health claims on the labels and in the labeling of their dietary supplements." Complaint ("Compl.") at 36. The plaintiffs' motion for summary judgment and the defendants' cross-motion for summary judgment are now before the Court. For the reasons explained below, the Court will grant in part and deny in part the parties' motions and remand certain claims to the FDA.
This case is the latest chapter in a lengthy saga of litigation concerning the FDA's regulation of the plaintiffs' marketing claims about the purported health benefits of various dietary supplements. Plaintiffs Durk Pearson and Sandy Shaw are scientists who design dietary supplement formulations and license them to manufacturers and retailers. Compl. ¶ 9. The other plaintiffs — the Coalition to End FDA and FTC Censorship and the Alliance for Natural Health US — are dietary supplement industry organizations. Id. ¶¶ 8, 10. The defendants are Kathleen Sebelius, in her official capacity as Secretary of the United States Department of Health and Human Services, the United States Department of Health and Human Services, Margaret A. Hamburg, M.D., in her official capacity as Commissioner of
In this case, the plaintiffs challenge an FDA decision declining to approve several health claims concerning the relationship between vitamins C and E and the risk for certain types of cancer. Before turning to the particular facts of this case, however, it is necessary to review the legal background underlying the parties' dispute and the previous court rulings that have addressed the issues involved here.
A "dietary supplement" is a "product (other than tobacco) intended to supplement the diet that bears or contains" one or more of certain dietary ingredients, including vitamins, minerals, herbs or botanicals, and amino acids. 21 U.S.C. § 321(ff)(1). A dietary supplement is deemed to be "food," which is defined in part as "articles used for food or drink for man or other animals," id. § 321(f)(1), except when it meets the definition of a "drug," which is defined in part as "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals." Id. § 321(g)(1)(B). A "health claim" is "any claim made on the label or in labeling of a food, including a dietary supplement, that expressly or by implication ... characterizes the relationship of any substance to a disease or health-related condition." 21 C.F.R. § 101.14(a)(1); see also 21 U.S.C. § 343(r)(1)(A)-(B).
In 1990, Congress enacted the Nutrition Labeling and Education Act of 1990 ("NLEA"), Pub. L. No. 101-535, 104 Stat. 2353 (1990) (codified as amended at 21 U.S.C. §§ 301, 321, 337, 343, 343-1, 345, 371), which amended the Food, Drug, and Cosmetic Act ("FDCA") to provide the FDA with authority to regulate health claims on food, including dietary supplements. Pearson v. Shalala, 164 F.3d 650, 653 (D.C.Cir.1999) ("Pearson I"). The NLEA created a "safe harbor" from the "drug" designation for foods and dietary supplements labeled with health claims. Alliance for Natural Health U.S. v. Sebelius, 714 F.Supp.2d 48, 51 (D.D.C.2010) ("Alliance I"); see also 21 U.S.C. § 343(r)(1). Under the NLEA, a manufacturer may make a health claim on a food without FDA new drug approval if the FDA determines that "significant scientific agreement," based on the "totality of publicly available scientific evidence," supports the claim. 21 U.S.C. § 343(r)(3)(B)(i). For dietary supplement health claims, however, Congress declined to establish an authorization process and instead left the creation of an approval "procedure and standard" to the FDA. Id. § 343(r)(5)(D). The FDA subsequently promulgated a regulation adopting the NLEA's standard for food health claims (i.e., "significant scientific agreement") for dietary supplement health claims. 21 C.F.R. § 101.14(c) ("FDA will promulgate regulations authorizing a health claim only when it determines, based on the totality of publicly available scientific evidence ... that there is significant scientific agreement ... that the claim is supported by such evidence."). The FDA may consider a dietary supplement labeled with an unauthorized health claim to be a misbranded food, 21 U.S.C. § 343(r)(1)(B); a misbranded drug, id.
The plaintiffs here and other individuals and groups affiliated with the production, sale, and use of dietary supplements have, for more than decade, sought judicial review of various FDA decisions denying a variety of proposed health claims. In the first of these lawsuits challenging the FDA's rejection of the plaintiffs' proposed claims on First Amendment grounds, the D.C. Circuit invalidated the FDA's then-existing approach to health claim review. Pearson I, 164 F.3d at 655-61. Since then, the FDA has struggled to balance its concerns for consumer protection and dietary supplement manufacturers' First Amendment commercial speech rights as defined by Pearson I. An abbreviated summary of these cases follows.
In 1995, a group of dietary supplement designers and others filed suit against the FDA and other defendants under the First Amendment, challenging the FDA's rejection of four health claims that the manufacturers sought to include on certain dietary supplements.
After the district court denied the supplement designers' motion for summary judgment, the D.C. Circuit reversed. The Court of Appeals, applying the commercial
In requiring the FDA to consider the adequacy of possible disclaimers accompanying the supplement designers' proposed health claims, the Court recognized that "where evidence in support of a claim is outweighed by evidence against the claim, the FDA could deem it incurable by a disclaimer and ban it outright." Id. at 659. Similarly, the Court "s[aw] no problem with the FDA imposing an outright ban on a claim where evidence in support of the claim is qualitatively weaker than evidence against the claim." Id. at 659 n. 10. However, the Court stated that the Agency "must still meet its burden of justifying a restriction on speech," and a "conclusory assertion" as to misleadingness is inadequate. Id. (citing Ibanez v. Fla. Dep't of Bus. & Prof'l Regulation, 512 U.S. 136, 146, 114 S.Ct. 2084, 129 L.Ed.2d 118 (1994) ("If the protections afforded commercial speech are to retain their force, we cannot allow rote invocation of the words `potentially misleading' to supplant the [government's] burden to demonstrate that the harms it recites are real and that its restriction will in fact alleviate them to a material degree.") (citations and internal quotation marks omitted)).
In late 2000, several of the plaintiffs from Pearson I and other dietary supplement designers, sellers, and manufacturers filed a second lawsuit to challenge the FDA's decision prohibiting plaintiffs from including on their dietary supplements' labels a health claim concerning folic acid.
The district court agreed with the plaintiffs, finding that the FDA "failed to comply with the constitutional guidelines outlined in Pearson [I]" when it concluded, without explanation, that the "weight of the evidence is against ... the proposed [folic acid] claim" and that the claim was therefore "inherently misleading" and not susceptible to correction by disclaimer. Id. at 112, 114. Although the court deferred to the FDA's "method of dissecting" and reading the folic acid claim per the APA, id. at 114 n. 24, it disagreed with the FDA's weighing of the scientific data and found "as a matter of law that [the folic acid claim] is not `inherently misleading.'" Id. In coming to this conclusion, the court analyzed the scientific data regarding folic acid and concluded that "[t]he mere absence of significant affirmative evidence in support of a particular claim ... does not translate into negative evidence `against' it." Id. at 115. Moreover, the court held that the "question which must be answered under Pearson [I] is whether there is any `credible evidence'" in support of the claim. Id. at 114, 118 (quoting Pearson I, 164 F.3d at 658). If so, unless that evidence is "outweighed by evidence against the claim" or is "qualitatively weaker" than evidence against the claim, the claim "may not be absolutely prohibited." Id. at 114-15.
Because the court found that there was credible evidence to support the folic acid claim, it held that the FDA's determination that the folic acid claim was "inherently misleading" and could not be cured by disclaimers was "arbitrary and capricious" under the APA and that the FDA had not "undertake[n] the necessary analysis required by Pearson [I]." Id. at 119. The court granted the plaintiffs' motion for a preliminary injunction and remanded the case to the FDA to "draft one or more appropriately short, succinct, and accurate disclaimers." Id. at 120.
After the preliminary injunction was entered in Pearson II, the FDA filed a motion for reconsideration, arguing that the district court had "assign[ed] undue weight to a particular clinical study and fail[ed] to consider the relevant scientific evidence in totality" and "creat[ed] a legal standard which is inconsistent with [Pearson I]." Pearson v. Thompson, 141 F.Supp.2d 105, 108 (D.D.C.2001) ("Pearson III"). The district court denied the motion, pointing
In June 2001, the plaintiffs filed another lawsuit to challenge the FDA's decision not to authorize an antioxidant claim that had been at issue in Pearson I.
Citing the Supreme Court's then-recent decision in Thompson v. Western States Medical Center, 535 U.S. 357, 122 S.Ct. 1497, 152 L.Ed.2d 563 (2002), the court held that the FDA had not met its "burden... to prove that its method of regulating speech [wa]s the least restrictive means of achieving its goals." Whitaker, 248 F.Supp.2d at 9 (citing Western States, 535 U.S. at 371-73, 122 S.Ct. 1497). Specifically, the court held that the FDA had failed to present evidence that the proposed antioxidant claim, "if accompanied by a disclaimer, would be deceptive or unlawful." Id. In coming to its conclusion, the court reviewed the FDA's analysis of the claim in light of Pearson I, noting that "[t]he deference due to an agency's expert evaluation of scientific data does not negate `the duty of the court to ensure that an agency... conduct a process of reasoned decision-making.'" Id. at 11 (quoting K N Energy, Inc. v. F.E.R.C., 968 F.2d 1295, 1303 (D.C.Cir.1992)). As such, the court reviewed over 150 intervention and observational studies regarding the relationship between antioxidant vitamins and cancer relied upon by the FDA in reaching its conclusions and found that nearly one-third of the studies "supported" the antioxidant/cancer relationship. Id. The court determined that the FDA had "failed to follow its own [Guidance] Report and give appropriate weight" to these studies. Id. at 12. Furthermore, the court held that the FDA had improperly emphasized and de-emphasized the import of certain studies, directly contrary to the protocol it established in the Guidance Report. Id. In short, the court concluded that the "basic finding" on which the FDA rested its denial of the proposed claim was "unreasonable because it [wa]s not supported by an overall review of the available evidence or the FDA's own Guidance Report." Id. at 13. The court then found that the circumstances under which the FDA might ban a claim as misleading, described in Pearson I, were not present because (1) one-third of the evidence examined supported
In Alliance for Natural Health U.S. v. Sebelius, 714 F.Supp.2d 48 (D.D.C.2010) ("Alliance I"), the same plaintiffs present in this action filed suit against the FDA challenging the FDA's denial of approval for certain health claims regarding the relationship between cancer risk and selenium supplements. Id. at 57. The plaintiffs had proposed their selenium health claims as "qualified" claims, which are health claims that include one or more disclaimers designed to eliminate potentially misleading assertions.
The plaintiffs objected both to the FDA's decision to ban certain claims entirely as well as to the FDA's modified claims, contending that, in both instances, the FDA violated the plaintiffs' First Amendment rights. Id. The plaintiffs contended that the language of the modified claims infringed their First Amendment rights by constructively suppressing their claims "with the imposition of an onerous, value laden set of qualifications that only allow Plaintiffs to propound a false, negatively value-laden, and inaccurate claim to the public." Id.
The Alliance I court, in applying the relevant analysis dictated by the Central Hudson test as elaborated by the D.C. Circuit in Pearson I, "conduct[ed] an independent review of the record ... without reliance on the [FDA's] determinations as to constitutional questions." Id. at 60. In accordance with binding precedent, however, the court gave "deference to the [FDA's] interpretation of scientific information, provided such interpretation [was] reasoned and not arbitrary or capricious." Id.
With respect to the claims that the FDA banned entirely, the Alliance I court began
With respect to the claims that the FDA permitted in modified form, the court agreed with the plaintiffs that the FDA's modified versions of the claims were "at odds with the Supreme Court's mandate that there be a `reasonable fit' between the government's goal and the restrictions it imposes on commercial speech." Id. at 71. The court found that "[t]he [FDA] has not drafted a `precise disclaimer' designed to qualify plaintiffs' claim while adhering to the `First Amendment preference for disclosure over suppression,' as mandated ... Rather, it has replaced plaintiffs' claim entirely. And the [FDA's] `qualification' effectively negates any relationship between... cancer risk and selenium intake." Id. (citation omitted). Accordingly, the court remanded "for the purpose of reconsidering the scientific literature and drafting one or more short, succinct, and accurate disclaimers in light of that review." Id. at 72.
The instant case is quite similar to Alliance I, except that it concerns different proposed health claims. On April 9, 2008, the plaintiffs submitted a petition to the FDA seeking approval of 17 qualified health claims linking vitamins C and E with a reduction in the risk of certain types of cancer.
Compl. ¶ 26. The FDA Decision banned Claims 1, 2, 3, and 4 outright and permitted Claim 5 (Vitamin C-gastric cancer) and Claim 6 (Vitamin E-bladder cancer) to be made as qualified claims with the following modified language:
Compl. ¶ 30; see also FDA Decision at A.R. 2510-11.
The plaintiffs brought this action on August 14, 2009 seeking a declaration that the FDA Decision violates their First Amendment rights. Compl. ¶ 1. The plaintiffs contend that their "qualified health claims ... [are] supported by credible scientific evidence," "[t]he scientific evidence for the claims is not outweighed by scientific evidence against them, and the claims are not inherently misleading." Id. ¶ 3. Accordingly, they contend that the FDA Decision violates their rights under the analysis set forth in Pearson I. Id.
The FDA filed the Administrative Record in this case on December 4, 2009.
The parties' cross-motions for summary judgment are now before the Court.
Pursuant to Federal Rule of Civil Procedure 56, the Court will grant a motion for summary judgment "if the movant shows that there is no genuine dispute as to any material fact and the movant is entitled to judgment as a matter of law" based upon the pleadings, depositions, and affidavits and other materials in the record. Fed. R.Civ.P. 56(a), (c); Tao v. Freeh, 27 F.3d 635, 638 (D.C.Cir.1994). In this case, there are no disputed issues of fact and each party seeks judgment as a matter of law based on the facts reflected in the administrative record.
Plaintiffs bring their claims under the First Amendment to the United States Constitution.
While the Court "is obligated to conduct an independent review of the record and must do so without reliance on the [FDA's] determinations as to constitutional questions," it must also give deference to an agency's assessment of scientific or technical data within its area of expertise. Id. at 60; see also Serono Labs., Inc. v. Shalala, 158 F.3d 1313, 1320 (D.C.Cir. 1998) (agency "evaluations of scientific data within its area of expertise" are "entitled to a high level of deference") (internal quotations omitted).
"[D]eference to the [the FDA's] interpretation of scientific information, provided such interpretation is reasoned and not arbitrary or capricious, is consistent with the test set forth in Pearson I." Alliance I, 714 F.Supp.2d at 60. "By instructing the FDA to employ less restrictive means of regulating speech and to provide greater empirical support for its regulatory decisions, the D.C. Circuit did not purport to tell the [FDA] how to assess scientific data. Rather, it provided the [FDA] with guidelines for developing regulations once it had evaluated the evidence before it."
Because the plaintiffs' qualified vitamin C and vitamin E health claims are commercial speech, the FDA's refusal to authorize them must be evaluated under the analytical framework established in Central Hudson, as elaborated upon by the D.C. Circuit in Pearson I and the Supreme Court in Western States. Id. at 60-61; see also Pearson I, 164 F.3d at 655.
Central Hudson established a multi-step analysis of speech regulation. "[A]s a threshold matter," the Court must determine "whether the commercial speech [being regulated] concerns unlawful activity or is misleading." Western States, 535 U.S. at 367, 122 S.Ct. 1497. If so, the speech is not protected. Id. But if the speech is lawful and not misleading, or is only potentially misleading, the Court must ask "whether the asserted governmental interest in regulating the speech is substantial." Id. (quoting Central Hudson, 447 U.S. at 566, 100 S.Ct. 2343). If it is, the Court then ascertains "whether the regulation [at issue] directly advances the governmental interest asserted" and, finally, "whether [the regulation] is not more extensive than is necessary to serve that interest." Id. (quoting Central Hudson, 447 U.S. at 566, 100 S.Ct. 2343). This last step requires the Court to evaluate "whether the fit between the government's ends and the means chosen to accomplish those ends is ... reasonable." Pearson I, 164 F.3d at 656 (citation omitted).
The government has the burden of showing that the regulations on speech that it seeks to impose are "not more extensive than is necessary to serve" the interests it attempts to advance. Western States, 535 U.S. at 371, 122 S.Ct. 1497 (quoting Central Hudson, 447 U.S. at 566, 100 S.Ct. 2343). "[I]f the Government c[an] achieve its interests in a manner that does not restrict [commercial] speech, or that restricts less speech, the Government must do so." Id. Therefore, the Court in Pearson I noted that disclaimers are "constitutionally preferable to outright suppression," Pearson I, 164 F.3d at 657, and that generally, "the preferred remedy is more disclosure, rather than less." Id. (quoting Bates v. State Bar of Arizona, 433 U.S. 350, 376, 97 S.Ct. 2691, 53 L.Ed.2d 810 (1977)); see also Pearson II, 130 F.Supp.2d at 113 ("[M]ore disclosure rather than less is the preferred approach, so long as advertising is not inherently misleading."). For this reason, the Court in Pearson I concluded that "when government chooses a policy of suppression over disclosure-at least where there is no showing that disclosure would not suffice to cure misleadingness-the government disregards a far less restrictive means." Pearson I, 164 F.3d at 658 (quotations omitted). However, the Court in Pearson I recognized that "where evidence in support of a claim is outweighed by evidence against the claim, the FDA could deem it incurable by a disclaimer and ban it outright." Id. at 659. Similarly, the Court "s[aw] no problem with the FDA imposing an outright ban on a claim where evidence in support of the claim is qualitatively weaker than evidence against the claim." Id. at 659 n. 10.
The plaintiffs contend that even where there is no credible evidence in support of claim, or where the evidence in support of the claim is qualitatively inferior, the FDA still may not ban a claim outright without proving with empirical evidence that a disclaimer cannot cure any misleadingness. See Pls.' Mem. at 21 (citing Whitaker, 248 F.Supp.2d at 5, 10). The FDA responds that there is no per se requirement to provide empirical evidence before disallowing a qualified health claim that is not supported by credible evidence, and that to
This Court agrees that Pearson I does not require the FDA to make an empirical showing of the inefficacy of a disclaimer before prohibiting a claim that is not supported by credible evidence. Regarding empirical evidence, the D.C. Circuit in Pearson I stated that "while we are skeptical that the government could demonstrate with empirical evidence that disclaimers similar to the ones we suggested above would bewilder consumers and fail to correct for deceptiveness, we do not rule out that possibility." 164 F.3d at 659-60. It is clear from the context of these remarks that the Court was referring to the disclaimers it had proposed to remedy the plaintiffs' potentially — although not inherently — misleading claims, which were based on credible, albeit inconclusive, evidence. In Pearson I, the FDA had argued that any allowance of health claims qualified by disclaimers would confuse consumers, see id. at 659, but the D.C. Circuit held that "the FDA's conclusory assertion" on this point failed to meet First Amendment burdens for justifying speech restrictions. Id. Nonetheless, the D.C. Circuit left open the possibility that "the government could demonstrate with empirical evidence that disclaimers similar to the ones [suggested by the Court] would bewilder consumers." Id. at 659-660. The D.C. Circuit did not hold, however, that a showing of empirical evidence was required in situations where the FDA could "reasonably determine" that a disclaimer would be insufficient because there was no credible evidence in support of the claim. See id. at 659 ("For example, if the weight of the evidence were against the hypothetical claim that `Consumption of Vitamin E reduces the risk of Alzheimer's disease,' the agency might reasonably determine that adding a disclaimer such as `The FDA has determined that no evidence supports this claim' would not suffice to mitigate the claim's misleadingness.").
Contrary to the plaintiffs' arguments, this Court does not agree that the D.C. Circuit intended to suggest that, before banning an unsupported claim, the FDA would have to conduct an empirical study on the efficacy of a disclaimer such as "The FDA has determined that no evidence supports this claim." Rather, the clear implication of the language of Pearson I is that unsupported or very weakly supported claims may simply be banned outright. See id. at 659 n. 10 ("[W]e see no problem with the FDA imposing an outright ban on a claim where evidence in support of the claim is qualitatively weaker than evidence against the claim..."). Presumably, such claims would qualify as unprotected commercial speech that can be prohibited under the threshold step of the Central Hudson analysis. See Central Hudson, 447 U.S. at 563, 100 S.Ct. 2343 ("The government may ban
The FDA Decision in response to the plaintiffs' petition banned plaintiffs from making four of the claims at issue here. See FDA Decision at A.R. 2475-76 (noting the FDA's determination that there is "no credible scientific evidence supporting" the vitamin C-lung cancer claim, the vitamin C-colon cancer claim, the vitamin E-lung cancer claim, and the vitamin E-gastric cancer claim). Under Central Hudson and Pearson I, the FDA may refuse to consider disclaimers for health claims (i.e., prohibit health claims completely) only if such claims are inherently misleading, or are potentially misleading but the FDA has determined the claim to be "incurable by a disclaimer." Pearson I, 164 F.3d at 659-60 (suggesting that government might completely ban health claim where "evidence in support of a claim is outweighed by evidence against the claim" or where it "demonstrate[d] with empirical evidence that disclaimers... would bewilder consumers and fail to correct for deceptiveness").
Here, the FDA justified its decision to ban these four claims based on the agency's determination that "there is no credible scientific evidence" supporting the claims. FDA Decision at A.R. 2475-76, 2503-2512. At a general level, such a decision appears consistent with Pearson I, which allowed for the possibility that "where evidence in support of a claim is outweighed by evidence against the claim, the FDA could deem it incurable by a disclaimer and ban it outright." 164 F.3d at 659. However, the Court in Pearson I also suggested that when "credible evidence" supports a claim, that claim may not be absolutely prohibited. Alliance I, 714 F.Supp.2d at 65; see also Pearson I, 164 F.3d at 658-59 (where "credible evidence" supported a proposed claim, "a clarifying disclaimer could be added" to note that the evidence was inconclusive). Therefore, as in Alliance I, this Court concludes that the proper inquiry here is whether the FDA properly determined that there was no "credible evidence" supporting the plaintiffs' claims. See Alliance I, 714 F.Supp.2d at 65. The Court "is not in the position, nor is it the Court's role, to independently assess whether the" scientific evidence evaluated by the FDA constitutes "credible evidence" in support of plaintiffs' claims. Id. at 66 n. 25. Rather, the Court must limit its consideration of this question to an assessment of whether the FDA's evaluation was inconsistent with its own standards, irrational, or arbitrary and capricious. Id.; see also Whitaker, 248 F.Supp.2d at 11 (reviewing FDA's evaluation of scientific evidence to ensure the FDA conducted a "process of reasoned decision-making" and that decision was not
In its 2009 Guidance Document, the FDA states that it uses an "evidence-based review system" to evaluate the strength of the evidence in support of a health claim. The process
2009 Guidance Document at A.R. 2426 (emphasis added). While the document does not explicitly define "credible," it does set forth threshold questions and principles that the FDA uses to prioritize certain types of evidence over others and to identify evidence from which relevant scientific conclusions may be drawn. For example, it states that "[r]andomized, controlled trials offer the best assessment of a causal relationship between a substance and a disease." Id. at A.R. 2428. By contrast, "research synthesis studies," and "review articles" "do not provide sufficient information on the individual studies reviewed" to determine critical elements of the studies and whether those elements were flawed. Id. at A.R. 2432. Similarly, animal and in vitro studies, while useful for background, "do not provide information from which scientific conclusions can be drawn regarding a relationship between the substance and disease in humans." Id. at A.R. 2432-33. The FDA also explains the questions it considers in determining whether scientific conclusions can be drawn from an intervention or observational study, such as where the studies were conducted (i.e., on what type of population); what type of information was collected; and what type of biomarker of disease risk was measured.
The Guidance Document's framework for assessing the evidence in support of proposed supplement health claims appears generally consistent with the requirements of Pearson I and Central Hudson. It is designed to sort claims into three different tiers: (1) authorized health claims, which are supported by "significant scientific agreement"; (2) qualified health claims, which are supported by credible evidence short of significant scientific
The plaintiffs contend that the 2009 Guidance Document has actually reinstituted a "de facto pre-Pearson I standard where only conclusive scientific proof can survive the FDA's claim review." In the plaintiffs' view, the FDA has simply shifted the focus to the question of what constitutes "credible" evidence and has adopted an overly restrictive standard of credibility. Pls.' Mem. at 12. While this concern is plausible, it is dispelled by the FDA's actual application of the Guidance Document. For example, in this case, the FDA Decision found four of the plaintiffs' claims to be supported by inconclusive yet credible evidence.
The Court also disagrees with the plaintiffs' argument that the FDA's approach is not based on a review of the totality of the scientific evidence because the FDA categorically discounts certain types of studies based on their methodology or design. See Pls.' Mem. at 12. Rather, the FDA's Guidance Document has articulated certain factors the agency will use in evaluating the totality of the scientific evidence, including factors indicating certain types of studies that do not provide credible evidence of health claims for supplement use in humans. The application of predefined principles for identifying which studies can
Using the procedure described in the Guidance Document, the FDA determined that there was no credible evidence to support the plaintiffs' vitamin C-lung cancer claim.
The FDA states that it discounted the Comstock and Gackowski studies because they used blood levels of vitamin C as a marker of vitamin C intake. FDA Decision at A.R. 2495-96, 2526. According to the FDA, "[s]ince circulating vitamin C or vitamin E levels and intake levels are poorly correlated, and many factors (e.g.,
The FDA discounted the Cho study because it was a "meta-analysis" of studies reflected in a review article. FDA Decision at 2523. As explained in the 2009 Guidance Document, "research synthesis studies," and "review articles," including "most meta-analyses," "do not provide sufficient information on the individual studies reviewed" to determine critical elements of the studies and whether those elements were flawed. 2009 Guidance Document at A.R. 2432. The Guidance Document makes an exception for meta-analyses "that review[] all the publicly available studies on the substance/disease relationship." Id. Based on the Court's review of the Cho article, the FDA's decision to exclude this article as a meta-analysis was not arbitrary and capricious. See Alliance I, 714 F.Supp.2d at 67. The article pooled information from only eight studies and actually concluded that "this pooled analysis of 8 prospective studies does not suggest that intakes of vitamins A, C, E, and folate reduce the risk of lung cancer." Cho at A.R. 752. Indeed, the study apparently found that "supplemental vitamin C alone [was] ... not associated with lung cancer risk." Id. at 751.
Finally, the FDA discounted the Feskanich and Neuhoser studies because they are observational studies that estimated vitamin intake "from dietary sources intake" — i.e., from the foods eaten by the study's subjects. FDA Decision at A.R. 2525, 2493-95. The FDA Decision contains an extensive discussion of why the FDA will not rely on food intake studies as evidence of a particular nutrient's effect on a disease. Id. at 2493-95. The reasons include numerous potential weaknesses in the methods for accurately measuring an individual's food intake, which are usually based on self-reporting; variability in the nutrient content of foods based on different farming, production, cooking, and storage conditions; difficulty in isolating the effects of various nutrient components of foods; and evidence of previous cases in which dietary intake studies had indicated that a food nutrient may have a beneficial effect on a disease, while subsequent intervention studies showed that dietary supplements containing that nutrient do not confer any benefit or actually increase risk of the disease. Id. The 2009 Guidance Document also notes these concerns and concludes that "scientific conclusions from observational studies cannot be drawn about a relationship between a food component and a disease." 2009 Guidance Document at A.R. 2438-39.
The plaintiffs object to the FDA's exclusion of observational studies based on food intake primarily because, according to the
The FDA directly addressed the D.C. Circuit's comments on this issue in its decision. FDA Decision at A.R. 2494. In short, the FDA contends that observational studies based on food intake do not provide "inconclusive" evidence of single nutrient supplement claims; rather, they simply do not support valid scientific conclusions about single nutrient supplements. Id. The reason for the FDA's conclusion is not only because of the difficulties in disentangling the effects of various food components, which was the issue addressed by the D.C. Circuit in Pearson I, but also because of all the other factors discussed above, particularly the understanding that nutrients in food do not necessarily have the same beneficial effect in supplement form, and that some studies have actually demonstrated increased disease risk from supplements predicted to be beneficial based on food studies. Id. As evidence of this understanding, which the FDA contends has emerged since the decision in Pearson I, the FDA points to a 2005 review article published in the Journal of the American Medical Association. Id.; see also Alice Lichtenstein and Robert Russell, Essential Nutrients: Food or Supplements?, 294 J. AM. MED. ASSOC. 351-58 (2005), at A.R. 3315-22.
This Court is persuaded that the FDA has provided a reasonable basis for determining that observational studies based on food intake do not provide credible scientific evidence of the disease risk effects of single nutrient supplements. To the extent that the FDA's concern about food studies is premised on the difficulty in isolating the effects of specific nutrient components of food, the D.C. Circuit did
Accordingly, the FDA's rejection of the studies cited by the plaintiffs as credible evidence of the claim that "Vitamin C may reduce the risk of lung cancer" was consistent with the FDA's established evaluation criteria and rationally justifiable based on the nature of the studies.
The FDA also determined the plaintiffs' vitamin C-colon cancer claim was not supported by credible evidence. Plaintiffs contend that the following five studies support their claim: Cahill et al. 1993, Bostick et al. 1993, Satia-Abouta et al. 2003, Chiu et al. 2003, and Olsen et al. 1994. Pls.' Mem. at 34-35; SMF ¶¶ 43-47.
The FDA did not credit the Cahill study as credible evidence because it measured effects that are not considered "validated surrogate endpoints of cancer risk" for colon cancer. FDA Decision at A.R. 2490, 2523. In other words, the study measured effects that are not proven indicators of the disease. According to the FDA, the only "validated endpoints" to use in evaluating risk reduction claims for colon cancer are (1) actual cases of colon cancer or (2) "recurrent adenomatous colorectal polyps," a medical condition involving colorectal polyps which are non-cancerous but which have proven to be correlated with colon cancer risk. FDA Decision at A.R. 2484, 2490. Put another way, a study that measures effects other than the incidence of colon cancer or adenomatous colorectal polyps (or other proven indicators of colon cancer risk) in the study population would not generally provide credible evidence for colon cancer risk claims. The Cahill study measured the effect of vitamin C supplementation on colon "crypt cell proliferation" in a group of ten patients that had existing colorectal polyps. Defs.' Mem. at 29 (citing Cahill at A.R. 2734-38). The study found that vitamin C supplements reduced the rate of crypt cell proliferation. Cahill at A.R. 2738. While higher rates of crypt cell proliferation are observed in patients with colon cancer or polyps, the study did not show that these higher rates of cell proliferation are themselves a cause of cancer or that reducing them affects cancer risk. Id. at 2737-38. While the Cahill authors hypothesized that the observed effect on cell proliferation in patients with colon polyps "may reduce the risk of progression" to cancer or recurrent adenomatous colon polyps, this proposition does not itself appear to have been validated by the study. See id. Under these circumstances, the Court finds that the
The FDA also excluded the other four studies cited by the plaintiffs because those observational studies estimated vitamin intake from dietary sources or from a combination of dietary sources and multivitamin supplements, a factor which provides a valid basis for exclusion, as discussed above. See Defs.' Mem. at 30; FDA Decision at A.R. 2525 (excluding Satia-Abouta et al. 2003, Bostick et al. 1993, Olsen et al. 1994, and Chiu et al. 2003).
Accordingly, the FDA's rejection of the studies cited by the plaintiffs' as credible evidence of the claim that "Vitamin C may reduce the risk of colon cancer" was consistent with the FDA's established evaluation criteria and rationally justifiable based on the nature of the studies.
The plaintiffs point to four studies in particular as evidence of their claim that vitamin E may reduce the risk for lung cancer: Woodson et al. 1999, Comstock et al. 1997, Knekt et al. 1991, and Lonn et al. 2005. Pls.' Mem. at 38-39; SMF ¶¶ 62-66.
The Lonn et al. 2005 study was an intervention study designed to "[t]o evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events." Lonn at A.R. 3346. The study was not specific to lung cancer and assessment of site-specific cancers was subsidiary. FDA Decision at A.R. 2487. The FDA discounted the study because it did not pre-screen subjects for specific cancers prior to the study, which the FDA contends may have resulted in biased incidences of lung cancer between the vitamin E group and the placebo group. Id. In any event, the main finding of the study, as stated by the authors, was "the lack of benefit for vitamin E in preventing cancer or major cardiovascular events after a prolonged period of treatment and observation." Lonn at A.R. 3351. In addition, the authors also concluded that "our study raises concern about an increased risk of heart failure related to vitamin E." Id. While the study authors did observe a decreased incidence of lung cancer in the vitamin E group, when the authors applied the relevant "stringent statistical rules," the difference in lung cancer rates did not rise to the predefined level of statistical
Plaintiffs point to five studies in particular to support their claim that vitamin E may reduce the risk of gastric cancer: Virtamo et al. 2000; You et al. 2000; Lopez-Carillo et al. 1999; Jenab et al. 2006b; and Buiatti et al. 1990. See Pls.' Mem. at 37; SMF ¶¶ 57-61.
The FDA validly discounted the Buatti and Lopez-Carillo studies because they estimated vitamin E intake based on food consumption. FDA Decision at A.R. 2525. The FDA also validly discounted the You and Jenab studies because they relied on serum or plasma levels of vitamin E as an indicator of intake. Id. at 2526. Finally, the FDA discounted the Virtamo article because, similar to the Lonn et al. 2005 study discussed above, the underlying trial was not designed to study gastric cancer risk and no pre-screening for gastric cancer was performed. Id. at 2524. Indeed, as the FDA points out in its brief, the Virtamo article does not relate to the effect of vitamin E on gastric cancer. Defs.' Mem. at 41 n. 32 (citing Virtamo at A.R. 3613-19). Rather, it relates to the effect of vitamin E on urinary tract cancer, and the authors concluded that vitamin E does not reduce the risk of urinary tract cancer.
In its decision, the FDA found that four of the qualified claims proposed by the plaintiffs were supported by some credible scientific evidence under the procedures for evidentiary analysis spelled out in the Guidance Document. FDA Decision at A.R. 2511-12. However, the FDA found that it needed to revise the wording of the plaintiffs' qualified claims "so as to not mislead consumers." Id. Plaintiffs challenge the FDA's rewording of two of their qualified claims here — the vitamin C-gastric cancer claim and the vitamin E-bladder cancer claim. As noted above, the FDA reworded these claims to read as follows:
As in Alliance I, "[t]he Court agrees with plaintiffs' contention that the FDA's proposed claim is at odds with the Supreme Court's mandate that there be a `reasonable fit' between the government's goal and the restrictions it imposes on commercial speech." Alliance I, 714 F.Supp.2d at 71 (citing Pearson I, 164 F.3d at 656 n. 5). Indeed, these disclaimers fail for the same reasons the disclaimers in Alliance I failed. The FDA has "not drafted [] `precise disclaimer[s]' designed to qualify plaintiffs' claim[s] while adhering to the `First Amendment preference for disclosure over suppression,' as mandated." Id. "Rather, it has replaced plaintiffs' claim[s] entirely." Id. Further, the FDA's "qualification" effectively negates any relationship between cancer risk and vitamin intake. See id. The FDA's rewording makes it difficult to tell what the original health claims are and appears to disavow the FDA's own conclusions that those claims are supported by credible evidence. "[T]he FDA has completely eviscerated plaintiffs' claim[s], with no explanation as to why a less restrictive approach would not be effective." Id. Where the evidence supporting a claim is inconclusive, the First Amendment permits the claim to be made; the FDA cannot require a disclaimer that simply swallows the claim.
For the reasons discussed above, the parties' motions for summary judgement are each granted in part and denied in part. The vitamin C-gastric cancer and vitamin E-bladder cancer claims are remanded to the FDA for further action consistent with this Memorandum Opinion and the other relief sought by the plaintiffs is denied.
