1 UNITED STATES DISTRICT COURT FOR THE DISTRICT OF COLUMBIA

__________________________________________ ) ALLIANCE FOR NATURAL HEALTH US , ) et al., ) Plaintiff s , ) ) v. ) Civil Action No. 09
- 01470 (ESH) ) KATHLEEN SEBELIUS, et al. , ) ) Defendan t s . ) __________________________________________)

MEMORANDUM OPINION Plaintiffs Alliance for Natural Health US, Durk Pearson, Sandy Shaw, and Coalition to End FDA and FTC Censorship have sued the Food and Drug Administration (“FDA” or “Agency”) and oth er defendants, 1

1 The other defendants named in the complaint are Kathleen Sebelius, Secretary, United States Department of Hea lth and Human Services (“DHHS”); DHHS; Margaret A. Hamburg, M.D., Commissioner, FDA; and the United States. seeking review of the Agency’s decision to deny plaintiffs’ petition for authorization of qualified health claims regarding selenium

- containing dietary supplements. Invoking both circuit and district court opinions that have addressed simi lar claims, p laintiffs seek a declaratory judgment that the FDA’s final order denying plaintiffs’ petition is invalid and a permanent injunction enjoining the Agency from “taking any action that would preclude [plaintiffs] from placing [their proposed sele nium] health claims on [dietary supple ment] labels.” (Compl. at 29 .) Before the Court are 1) plaintiffs’ motion for summary judgment and 2) defendants’ cross

- motion for summary judgment. For the reasons set forth herein, the Court will grant plaintiffs’ motion in part and deny defendants’ motion.2 BACKGROUND
I. STATUTORY AND REGULATORY FRAMEWORK A “dietary supplement” is a “product (other than tobacco) intended to supplement the diet that bears or contains” one or more of certain d ietary ingredients, includi ng vitamin s , mineral s , herb s or botanical s , amino acid s , concentrate s , metabolite s , constituent s , or extract s . 21 U.S.C. § 321(ff)(1)(A)

- (F). A d ietary supplement is deemed to be “food,” id. § 321(ff), 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)

. ( See also De fs.’ Cross

- Mot. for Summ. J. & Opp’n to Pls.’ Mot. for Summ. J. [“Defs.’ Mot.”] at 3 n.2)

. A “health claim” is “any claim made on the label or in labeling of a food, including a dietary supplement, that expressly or by imp lication . . . 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). Under the Federal Food, Drug, and Cosmetic Act (“FFDCA”), m anufacturers wishing to market a new drug must undergo a “strict and demanding” process designed to ensure consumer safety and product efficacy in order to obtain FDA approval before introducing the product into interstate commerce

. Weinberger v. Hynson, Westcott & Dunning, Inc

. , 412 U.S. 609, 618

- 19 (1973) ; see also 21 U.S.C. § 355(a); Pearson v. Shalala , 164 F.3d 650, 652 (D.C. Cir. 1999) (“ Pearson I ”)

. “ Prior to 1984 , the FDA took the position that a statement that consumption of a food could pr event a particular disease was ‘ tantamount to a claim that the food was a drug . . . and therefore that its sale was prohibited until a new drug application had been approved. ’ ”
Pearson I , 164 F.3d at 653 (quoting H.R. Rep. No

. 101

- 538, at 9 (1990), reprinted in 19903 U.S.C.C.A.N. 3336 , 3338). But in the mid

- 1980s, companies began making health claims on foods without seeking new drug approval, a practice the FDA supported. Id. Congress subsequently enacted the Nutrition Labeling and Education Act of 1990 (“NLEA”), Pub. L. No. 101

- 53 5, 104 Stat

. 2353 (1990) (codified as amended at 21 USC §§ 301, 321, 337, 343, 343

- 1, 345, 371), amending the FFDCA to provide the FDA with authority to regulate health claims on food. Pearson I , 164 F.3d at 653. The NLEA created a “safe harbor” from t he “drug” designation for foods and dietary supplements labeled with health claims. Pearson v. Shalala , 130 F. Supp. 2d 105, 107 (D.D.C. 2001) ( “Pearson II ”); see also 21 U.S.C. § 343(r)(1)

. Under the Act, 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, howeve r, 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 cl aims ( i.e. , “significant scientific agreement”) for dietary supplement health claim s . 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 eviden ce . . . 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 misbra nded drug, id. § 352(f) ; and/or an unapproved new drug. Id. § 355(a). A dietary supplement labeled with such a claim, or a claim that is false or misleading, is subject to seizure,4 and the Agency may enjoin the product’s distribution or seek criminal pen alties against its manufacturer. Id. §§ 331(a), 332, 334, 352(a) ; see also Def.’s Mot. at 3

.

II. PEARSON V. SHALALA AND SUBSEQUENT CASE LAW A. Introduction Plaintiffs’ lawsuit is the latest in a series of disputes between dietary supplement designers and the FDA regarding the Agency’s regulation of health claims regarding dietary supplements after the passage of the NLEA . Pearson, Shaw, and other individuals and groups affiliated with the production, sale, and use of dietary supplements have , since 1995, soug ht judicial review of FDA decisions denying a variety of proposed health claims . The first of these lawsuits, challenging the FDA’s rejection of the plaintiffs’ proposed claims on First Amendment grounds, resulted in an invalidation of the Agency’s regula tions regarding health claim review by the D.C. Circuit. Pearson I , 164 F.3d at 661. Since then, the FDA has struggled to balance its concerns for consumer protection and dietary supplement manufacturers’ First Amendment commercial speech rights as defin ed by Pearson I

. An abbreviated summary of these cases follows.
B. Pearson I In 1995 , a group of dietary supplement manufacturers 2 filed suit against the FDA and other defendants under the First Amendment , challenging the FDA’s rejection of four health cla ims 3

2 Two of these plaintiffs , Pearson and Shaw, are plaintiffs in the instant case. that the manufacturers sought to include on certain dietary supplements. Pearson v.

3 Pearson I concerned the FDA’s rejection of the following healt h claims: (1) “Consumption of antioxidant vitamins may reduce the risk of certain kinds of cancers”; (2) “Consumption of fiber may reduce the risk of colorectal cancer”; (3) “Consumption of omega

- 3 fatty acids may reduce5 Shalala , 14 F. Supp. 2d 10, 14 (D.D.C. 1998). The claims characterized a relationship between dietary supplements and the risk of particular diseases. Id. The Agen cy, applying the “significant scientific agreement” standard set forth in 21 C.F.R. § 101.14 , determined that the evidence concerning the supplements “was inconclusive . . . and thus failed to give rise to ‘significant scientific agreement.’” Pearson I , 1 64 F.3d at 653. T he Agency therefore declined to authorize the claims, finding the m to be “ inherently misleading and thus entirely outside the
pr otection of the First Amendment ” as commercial speech. Id. at 655 (emphasis in original)

. The FDA also decli ned to consider the proposed alternative of “permitting the claim [s] while requir ing . . . corrective disclaimer [s] , ” arguing that even if the proposed claims were only “potentially misleading,” it had no obligation under the First Amendment to consider a “disclaimer appr oach,” as opposed to suppression , where the claims at issue lack ed significant scientific agreement

. Id. at 654 , 655, 657

. The manufacturers sued, arguing that the FDA’s “significant scientific agreement” standard was unconstitutionally v ague and was tantamount to a b lanket ban on commercial speech in violation of the manufacturers’ First Amendment rights. 4

After the district court denied the manufacturers’ motion for summary judgment , the D.C. Circuit rev ersed. The Court, applying the commercial speech test set forth in Central Hudson Pearson , 14 F. Supp. 2d at 14.

the risk of coronary heart disease ”; and (4) “ .8 mg of folic acid in a dietary supplement is more effective in reducing the risk of neural tube defects than a lower amount in foods in common form .” Pearson I , 164 F.3d at 652.

4 The manufacturers also argued that the “significant scient ific agreement” standard for dietary supplement health claims generally and as applied to the four claims proposed by plaintiffs violated the NLEA and the Administrative Procedure Act (“APA”). Pearson , 14 F. Supp. 2d at 14.6 Gas & Electric Corporation v. Public Service Commission of New York , 447 U.S. 557 (1980), 5

In requiring the Agency to co nsider the adequacy of possible disclaimers accompanying the manufacturers’ 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 held that there was not a “reasonable fi t between the government’s goals” of prote cting public health and preventing consumer fraud and “the means chosen to advance those goals,” namely, the rejection of plaintiffs’ proposed health claims without consideration of disclaimers. Pearson
I , 164 F.3d at 656

- 58. Specifically, the Court held that under the First Amendment commercial speech doctrine, there is a “preference for disclosure over outright suppression” and for “less restrictive and more precise means” of regulating commercial speech. Id. at 657

- 58. The Agency’s rejection of discl aimers without a showing that they were insufficient to meet the government’s goal of avoiding consumer confusion demonstrated a disregard for “less restrictive” means of speech regulation that violated the First Amendment. T he Court remanded the case to the district court with instructions to remand it to the Agency to consider whether disclaimers could sufficiently prevent consumer confusion and , if so, the content of those disclaimers

. Id. at 659. The Court also held that the APA requires the FDA to “ giv[e] some definitional content to the phrase ‘significant scientific agreement,’” because to “declare

- without explanation

- that a proposed course of private action is not approved” is arbitrary and capricious. Id. at 660

- 61.

5 The Central Hudson analysi s, as clarified by the Supreme Court in Thompson v. Western States Medical Center , 535 U.S. 357 (2002), consists of four parts: 1) “whether ‘ the speech concerns lawful activity and is not misleading; ’ ” 2) if the speech is protected, “whether the asserted g overnment interest [in regulation] is substantial;” 3) “whether the regulation directly advances the governmental interest asserted;” and 4) “whether [the regulation] is not more extensive than is necessary to serve that interest.” Whitaker v. Thompson , 2 48 F. Supp. 2d 1, 8

- 9 (D.D.C. 2002) (quoting Western States , 535 U.S. at 367; Pearson I , 164 F.3d at 657).7 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 Co urt 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 (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 i n fact alleviate them to a material degree.”) (citations and internal quotation marks omitted) )

. C. Pearson II In late 2000, several of the plaintiffs from Pearson I and other dietary supplement designers, sellers, and manufacturers 6 filed a second lawsu it to challenge the Agency’s decision prohibiting plaintiffs from including on their dietary supplements’ labels a health claim concerning folic acid. 7

6 The p laintiffs in Pearson II were Durk Pearson; Sandy Shaw; American Preventive Medical Association; Julian M. Whitaker, M.D .; Pure Encapsulation s, Inc.; and XCEL Medical Pharmacy, Ltd. Pearson II , 130 F. Supp. 2d at 107 n.1. Pearson v. Shalala , 130 F. Supp. 2d 105, 107 (D.D.C. 2001) ( “ Pearson

7 The folic acid health claim at issue in Pearson II was the same folic acid claim at issue in Pearson I , which stated that “.8 mg of folic acid in a dietary supplement is more effective in reducing the risk of neural tube defects than a lower amount in foods in common form

. ” Pearson I , 164 F.3d at 652. With respect to this claim, the Court of Appeals in Pearson I “strongly suggested, without declaring so explicitly” th at the claim “was only ‘potentially misleading,’ not ‘inherently misleading,’ and therefore the FDA’s refusal to authorize [the claim] (or to propose a disclaimer to accompany the [c]laim) violated the First Amendment.” Pearson II , 130 F. Supp. 2d at 110 ; see also Pearson I , 164 F.3d at 659 (“[I]t appears that credible evidence did support [the folic acid claim], and we suspect that a clarifying disclaimer could be added to the effect that ‘The evidence in support of this claim is inconclusive

. ’” (citation omitted)).8 II

”). After the decision in Pears on I , the FDA published a notice requesting submission of scientific data concerning the four health claims at issue in that case, including the folic acid claim

. Id. at 110. The Agency also issued “Guidance for the Industry: Significant Scientific Agree ment in the Review of Health Claims for Conventional Foods and Dietary Supplements

. ” 8
Id. at 111. After reviewing the newly submitted scientific data and applying the “significant scientific agreement standard” described in its guidance document and modi fied by an October 6, 2000 rule, 9

The district court agreed with the plaintiffs , finding that the FDA “failed to comply with the constitutional guidelines outlined in Pearson [I] ” wh en it concluded, without explanation, the Agency issued a decision stating that it would not authorize the manufacturers’ folic acid claim, even with clar ifying disclaimers, because it found the claim to be inherently misleading. Id. T he plaintiffs argued th at the Agency’s decision “fundamentally misread and misapplied the legal standard articulated” in Pearson I and violated the First Ame ndment, the FFDCA, and the APA. Id. at 107, 1 12. T hey sought a preliminary injunction “enjoining the FDA from taking any action which would prevent Plaintiffs from using their desired folic acid health claim.” Id. at 107.

8 The current FDA guidance regarding evaluation of health claim s, issued in 2009, is entitled “Guidance for Industry: Evidence

- Based Review System f or the Scientific Evaluation of Heal th Claims ” [hereinafter “Guidance Document”]. (Admin istrative Record [“AR”] 00 3508.)

9 On October 6, 2000, the FDA published a notice stating that “[r]ather than denying all petitions that do not meet the significant scientific agreement standard pending completion of the general rulemaking,” it would in stead “exercise enforcement discretion in appropriate circumstances,” such as when “the scientific evidence in support of [a] claim outweighs the scientific evidence against the claim, the claim is appropriately qualified, and all statements in the claim a re consistent with the weight of the evidence . . . .” 65 Fed. Reg. 59855, 59856 (Oct. 6, 2000).9 that the “weight of the evidence is against both aspects 10

Because the court found that there was credible ev idence 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 no t “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. of 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 c ourt deferred to the Agency’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 c ourt 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 i nto 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 6 58). If so, unless that evidence is “outweighed by evidence against the claim” o r is “qualitatively weaker” than evidence against the claim, the claim “may not be absolutely prohibited.” Id. at 114

- 15

.

10 The court considered whether .8 mg of folic acid is superior to .4 mg and whether folic acid is superior to folate found in foods in common form in preve nting neural tube defects. Pearson II , 130 F. Supp. 2 d at 115, 117

.10 D. Pearson III 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 parti cular clinical study and fail[ed] to consider the relevant scientif ic 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 denied the motion, pointing to the FDA’s “fail[ure] to fully and a ccurately describe the record evidence” and “speculative” arguments. Id. at 109. The district court also restated the holdings in Pearson I , which included 1) the obligation of the Agency to “demonstrate with empirical evidence that disclaimers . . . wou ld bewilder consumers and fail to correct for deceptiveness,” id. at 112 (quoting Pearson I , 164 F.3d at 659

- 60, and 2) the establishment of “a very heavy burden which Defendants must satisfy if they wish to totally suppress a particular health claim.” Id

. E. Whitaker v. Thompson In June 2001, the plaintiffs 11 filed another lawsuit to challenge the Agency’s decision not to authorize the antioxidant claim at issue in Pearson I

. 12

11 The p laintiffs in Whitaker were Julian M. Whitaker, M.D .; Durk Pearson; Sandy Shaw; American Association for Health Freedom ; Wellness Lifestyles, Inc.; and Pure Encapsulations, Inc. Wh itaker v. Thompson , 248 F. Supp. 2d 1, 2 n.1 (D.D.C. 2002). Whitaker , 248 F. Supp. 2d at 2 , 7

. The Agency, after reviewing the antioxidant

- c ancer relationship studies submitted at its request subsequent to Pearson I , “found a lack of significant scientific agreement as to the relationship between antioxidant vitamin intake and reduction in the risk of developing cancer.” Id. at 7. T he
FDA co ncluded “that the weight of the scientific evidence against the relationship [between cancer and antioxidant vitamins] was greater than the weight of evidence in favor of the

12 The claim at issue was that “Consumption of antioxidant vitamins may reduce the risk of certain kinds of cancers.” Whitaker , 248 F. Supp. 2d at 2; see also Pearson I , 164 F.3d at 652.11 relationship” and, similar to its analysis of the folic acid claim in Pearson I a nd II , it determined that the plaintiffs’ antioxidant claim was therefore “inherently misleading and c[ould not] be made non

- misleading with a disclaimer or other qualifying language.” Id. ; see also Pearson II , 130 F. Supp. 2d at 111

- 12. Plaintiffs argue d that the Agency had again misapplied the standard articulated in Pearson I in violation of the First Amendment, and the district court agreed. Id. at 7

- 8. Citing the Supreme Court’s then

- recent decision in Western States , the court held that the Agenc y h ad not met its “burden . . . to prove that its method of regulating speech [wa]s the least restrictive means of achieving its goals.” Id. at 9 (citing Western States , 535 U.S. at 371

- 73). 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 Agency’s analysis of the claim in light of
Pearson I , noting that “[t]he deference du e 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. 199 2)). 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 “supporte d” 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 a nd 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 proposed12 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 Agency might ban a claim as misleading, described in Pearson I ,
were not present because 1) one

- third of the evidence examined supported the claim; and 2) the FDA failed to provide “empirical evidence that an appropriate disclaimer would confuse customers and fail to correct for deceptiveness.” Id. As a result, the court granted a preliminary injunction after concluding that the Agency’s decision to suppress the claim did not “comport with the First Amendment’s clear preference for disclosure over suppression of commercial speech .” Id. at 15, 17 (remanding case to FDA to draft “short, succinct, and accurate alternative disclaimers”).
III. FACTUAL AND PROCEDURAL HISTORY In July 2002, Wellness Lifestyles, Inc., one of the plaintiffs in Whitaker , submitted to the FDA two proposed health claims regarding the relationship b etween selenium and cancer risk

. On February 21, 2003, the FDA exercised enforcement discretion with respect to two “qualified” 13 versions of the health claims. 14

13 “Qualified health claims” are health claims that include one or more disclaimers designed to eliminate potentially misleading assertions. They were created in response to the D.C. Circuit’s holding in Pearson I

. ( See FDA, Guidance for Industry: Evide nce - Based Review System for the Scientific Evaluation of Health Claims [“2009 Guidance Document”], at FDA 003510.) (Pls.’ Statement of Uncontested Material Facts

14 The original proposed health claims were 1) “Selenium may reduce the risk of certain cancers;” and 2) “Selenium may produce anticarcinoge nic effects in the body.” (Petition for Health Claims: Selenium and Reduction in the Risk of Certain Cancers; Selenium and Anticarcinogenic Effects (July 10, 2002), available at http://www.fda.gov/ohrms/dockets/dailys/02/Oct02/101802/800330ab.pdf (last vi sited May 25, 2010). The FDA concluded that the petition “d[id] not meet the ‘significant scientific agreement standard’” but ultimately exercised enforcement discretion with respect to qualified versions of the claims that stated as follows: 1) “Seleni um may redu ce the risk of certain cancers. Some scientific evidence suggests that consumption of selenium may reduce the risk of certain forms of cancer. However, FDA has determined that this evidence is limited and not conclusive;” and13 [“Pls.’ SMF”] ¶ 10.) In December 2007, the F DA, in response to an Agency for Healthcare Research and Quality (“AHRQ”) study, announced its intention to “ reevaluate the scientific evidence on these two qualified health claims and determine if the scientific evidence continues to support the qualified health claim, and if so, whether the qualified health claim language should be modified to reflect a stronger or weaker relationship. ” 72 Fed. Reg. 72738, 72739 (Dec. 21, 2007). The Agency commenced a public comment period on this issue, and plaintiffs filed extensive comments in opposition to the FDA’s proposed re

- evaluation of the two selenium claims. (Pls.’ SMF ¶ 14.) 15 In addition to opposing the FDA’s planned re

- evaluation of the qualified selenium health claims, p l aintiffs submitted a health cl aim petitio n seeking authorization of ten new qualified health claims (collectively, “qualified selenium health claims”) 16

2) “Selenium may produce anticarcinogenic effects in the body. Some scientific evidence suggests that consumption of selenium may produce anticarcinogenic effects in the body. However, FDA has determined that this evidence is limited and not conclusive.” (Pls.’ SMF ¶ 10 ; Selenium and Certain Cancers (Qualified Health Claim: Final Decision Letter) (Docket No. 02P

- 0457) (Apr. 28, 2003), available at http://www.fda.gov/Food/LabelingNutrition/LabelClaims /QualifiedHealthClaims/ucm072780 .ht m (last visited May 25, 2010)). concerning the purported

15 Plaintiffs’ opposition was not addressed by the Agency in its response to plaintiffs’ petition (Letter from Barbara O. Schneeman, Director, Office of Nutrition, Labeling and Dietary Supplements, Center for Food Safety and Applied Nutrition, FDA to Jonathan W. Emord (June 19, 2009) [“FDA Resp.”] at AR 001959), nor is it a subject of plaintiffs’ complaint.

16 Plaintiffs proposed the following claims: 1. Selenium may reduce the risk of certain cancers. Scientific evidence supporting this claim is convincing but not yet conclusive.
2. Selenium may produce anticarcinogenic effects in the body. Scientific evidence supporting this claim is convincing but not yet conclusive.
3. Selenium may reduce the risk of prostate cancer. Scientific evidence supporting this claim i s convincing but not yet conclusive.14 relationship between selenium and cancer. ( Petition for Qualified Health Claims: Selenium and the Reduction in the Risk of Site

- Specific Cancers [“Petition”] at AR 000001, 000022.) Plaintiffs’ submission included over 150 scientific articles purporting to examine one or more aspects of the relationship between selenium and cancer , which supplemented the 17 arti cles previously submitted to the FDA during the public comment period

. 17

After conducting a comprehensive review of the petition and posting it on the FDA website for a 60

- day comment period, t he Agency responded i n June 2009. ( FDA Resp. at AR 001957

- 002012.) The FDA concluded that while scientific evidence supports qualified health claims concerning the relationship between selenium intake and a reduced risk of bladder, ( See FDA Resp. at AR 001967

- 001968.)

4. Selenium may reduce the risk of bladder and urinary tract cancers. Scientific evidence supporting this claim is convincing but not yet conclusive.
5. Selenium may reduce the risk of lung and respiratory tract cancers. Scientific evidence supporting this claim is convincing but not yet conclusive.
6. Selenium may reduce the risk of colon and digestive tract cancers. Scientific evidence supporting this claim is convincing but not yet conclusive.
7. Selenium may reduce the ri sk of thyroid cancer. Scientific evidence supporting this claim is convincing but not yet conclusive.
8. Selenium may reduce the risk of brain cancer. Scientific evidence supporting this claim is convincing but not yet conclusive.
9. Selenium may reduce the risk of liver cancer. Scientific evidence supporting this claim is limited and applies only to hepatitis B virus

- induced forms of the disease.
10. Selenium may reduce the risk of breast cancer. Scientific evidence supporting this claim is convincing but not yet conclusive. (Petition at AR 000045.)

17 Plaintiffs also submitted three supplements to their petition including “recent publications on selenium and cancer chemoprevention” and “an analysis and opinion of a recent publication of the National Cancer I nstitute (NCI) Selenium and Vitamin E Prevention Trial.” (FDA Resp. at AR 001958.)15 prostate, and thyroid cancer, no such evide nce exists to support a relationship between selenium intake and a reduced risk of urinary tract (other than bladder), lung and other respiratory tract, colon and other digestive tract, brain, liver, and breast cancers. ( Id. at AR 001959.) The Agency als o concluded that proposed Claims 1 and 2, regarding selenium intake and certain cancers and anticarcinogenic effects, “are misleading because they are overbroad, fail to disclose material information, and are not supported by the scientific evidence the ag ency reviewed . . . .” 18 ( Id. ) Accordingly, the FDA denied Claims 1, 2, 5, 6, 8, 9, and 10 and stated that it would exercise enforcement discretion with respect to modified versions of Claims 3, 4, and 7. 19

Plaintiffs filed the instant lawsuit on August 4, 2009, claiming a violation of the First Amendment as a result of the FDA’s denial of Claims 1 ( “certain cancers claim”); 2 ( “anticarcinogenic effects claim”); 5 (“lung/respiratory tract claim”); and 6 ( “colon/digestive ( Id. at AR 001992

- 001993.)

18 In its response letter, the Agency also summarized the process by which it reviewed plaintiffs’ petition ( id. at AR 001959

- 001960); the weight it accords certain types of scientific studies ( id. at AR 001960

- 001962); its definition of the term “cancer” and its application to Claims 1 and 2 ( id. at AR 001962

- 001965); its safety review of selenium ( id. at AR 001965

- 001976); its assessment of the various studies submitted i n support of the various claims in the petition ( id. at AR 001968

- 001987); the strength of the scientific evidence ( id. at AR 001987

- 001990); other enforcement discretion factors ( id. at AR 001990

- 001992); its consideration of disclaimers or qualifying lan guage ( id. at AR 001992); and its conclusions ( i d. at AR 001992

- 001994 )

. 19 The Agency stated that it would consider the exercise of its enforcement discretion for the following qualified health claims: 1) “One study suggests that selenium intake may redu ce the risk of bladder cancer in women. However, one smaller study showed no reduction in risk. Based on these studies, FDA concludes that it highly uncertain that selenium supplements reduce the risk of bladder cancer in women;” 2) “Two weak studies sug gest that selenium intake may reduce the risk of prostate cancer. However, four stronger studies and three weak studies showed no reduction in risk. Based on these studies, FDA concludes that it is highly unlikely that selenium supplements reduce the ris k of prostate cancer;” and 3) “One weak, small study suggests that selenium intake may reduce the risk of thyroid cancer. Based on this study, FDA concludes that it is highly uncertain that selenium supplements reduce the risk of thyroid cancer.” (FDA Re sp. at AR 001993.)16 tra ct claim”)

. (Compl. ¶¶ 56

- 63). Plaintiffs also maintain that the FDA’s modification of Claim
3 ( “prostate claim ”) violates their First Amendment rights because it “constructively suppress[es] [this] claim with the imposition of an onerous, value laden se t of qualifications that only allow Plaintiffs to propound a false, negatively value

- laden, and inaccurate claim to the public.” ( Id. ¶ 67.) Plaintiffs also oppose the FDA’s proposed qualifications of Claim 3 as being “unreasonably long and burdensome fo r Plaintiffs and other industry members to include on their dietary supplement labels,” thereby violating Central Hudson ’s requirement that the governments means of accomplishing i ts goals be reasonable. ( Id. ¶ 67.) They seek : 1) a declaratory judgment t hat the FDA’s June 19, 2009 final order denying plaintiffs’ petition is invalid ; 2) an order that the FDA “refrain from taking any action” precluding plaintiffs from placing Claims 1, 2, 3, 4, and 5 on selenium dietary supplement labels; and 3) a permanent injunction, enjoining the FDA from taking any action precluding plaintiffs from placing Claims 1, 2, 3, 4, and 5 on selenium dietary supplement labels. ( Id. at 28

- 29.)

ANALYSIS
I. LEGAL STANDARD A. Scope of Review Plaintiffs raise their claims under the Fir st Amendment to the United States Constitution

. 20

20 The Court “has the authority to examine and rule on any actions of a federal agency that allegedly violate the Constitution,” apart from the power of review granted by the Administrative Procedure Act (“APA”)

. Rydeen v. Quigg , 748 F. Supp. 900, 905 (D.D.C. 1990) , aff’d mem. , 937 F.2d 623 (Fed. Cir. 1991) (citing Porter v. Califano , 592 F. 2d 770, 780 (5th Cir. 1979)). However, the APA “also provides for the Courts to make an independent assessment of constitutional issues,” and the role of the Court is the same “whether the plaintiff sues directly under the Constitution or under [the APA].” Id. at 905 n.8 (citing 5 U.S.C. § 706(2)(b)). (Compl. ¶¶ 56

- 67). “[A] Court’s review of ‘constitutional challenges to agency17 actions . . . is de novo .’” Poett v. United States , 657 F. Supp. 2d 230, 241 (D.D.C. 2009) (quoting Cullman Reg’l Med. Ct r. v . Shalala , 945 F. Supp. 287, 293 (D.D.C. 1996)). The Court shall make “an independent assessment of [the plaintiffs’] claim of constitutional right when reviewing agency decision

- making,” Porter , 592 F. 2d at 780 , and it need not accord deference to the ag ency’s “pronouncement on a constitutional question.” J.J. Cassone Bakery, Inc. v. NLRB , 554 F.3d 1041, 1044 (D.C. Cir. 2009) (quoting Lead Indus. Ass’n Inc. v. EPA , 647 F.2d 1130,
1173

- 74 (D.C. Cir. 1980) (emphasis added) )

. The parties disagree as to wh ich standard the Court should apply in reviewing the Agency’s decision to deny the majority of plaintiffs’ qualified selenium health claims. Plaintiffs maintain that “[r]eview of an agency action does not default to arbitrary and capricious review when a constitutional issue is raised even if it is raised under the APA ,” (Pls.’ Mem. in Reply and Opp’n to Def.’s Opp’n to Pls.’ Mot. for Summ. J. and Cross

- Mot. for Summ. J. [“Pls.’ Reply”] at 13), and therefore a more stringent standard applies, “not the defe rential Chev ron U.S.A., Inc. v. Natural Resources Defense Council , 467 U.S. 837 (1984) or [APA] standards.” (Pls.’ Mem. in Supp. of Mot. for Summ. J. [“Pls.’ Mot.”] at 18.) The Agency contends that because “this case does not involve a challenge to a reg ulation broadly prohibiting an entire category of misleading speech” and instead involves “ particularized findings concerning the scientific evidence relating to plaintiffs’ specific health claims,” the “APA’s deferential [arbitrary and capricious] standar d applies here.” (Defs.’ Mot. at 22.) This disagreement has been ongoing since Pearson I was decided. See Pearson II , 130 F. Supp. 2d at 115 n.25. In Pearson II , the district court decided it need not reach this issue because it found that the Agency’s decision in that case violated both standards. Id. In Whitaker , the court did not address the disagreement directly. Instead, it acknowledged the “deference due to an agency’s expert evaluation of scientific data” but18 concluded that such deference did not negate the court’s obligation to ensure that the agency engaged in reasoned decision

- making and that its reasoning was not “‘arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law.’” 248 F. Supp. 2d at 11 (quoting 5
U.S. C. § 706(2)(A)). The court went on to review the scientific evidence evaluated by the FDA and concluded that the FDA’s finding on which it rested its decision to deny plaintiffs’ proposed health claim was “unreasonable” because that finding was “not suppo rted by an overall review of the available evidence or the FDA’s own Guidanc e R eport.” Id. at 13. The Court concludes that it is obligated to conduct an independent review of the record and must do so without reliance on the Agency’s determinations as to constitutional questions. See J.J. Cassone Bakery, Inc. , 554 F.3d at 1044 (constitutional challenges to agency actions are “entertain[ed] . . . de novo ”). But it would be inconsistent with binding precedent and wholly inappropriate to evaluate the volum inous scientific studies at issue in this case without some deference to the FDA’s assessment of that technical data. See , e.g. , Marsh v. Or. Natural Res. Council , 490 U.S. 360, 377 (1989) (“Because analysis of the relevant documents requires a high level of technical expertise, we must defer to the informed discretion of the responsible federal agencies.”) (internal citation and quotations omitted); Serono Labs., Inc. v. Shalala , 158 F.3d 1313, 1320 (D.C. Cir. 1998) (agency “evaluations of scientific data with in its area of expertise” are “entitled to a high level of deference”) (internal quotations omitted); A.L. Pharma, Inc. v. Shalala , 62 F.3d 1484, 1490 (D.C. Cir. 1995) (“[C]ourts give a high level of deference to an agency’s evaluations of scientific data within its area of expertise.”); see also J.J. Cassone Bakery, Inc. , 554 F.3d at 1044 (distinguishing between “other aspects of a[n agency] decision, which we review deferentially” and “a constitutional question,” to which “a reviewing court owes no d eference”). Moreover, deference to the Agency’s interpretation of scientific19 information, provided such interpretation is reasoned and not arbitrary or capricious, is consistent with the test set forth in Pearson I . 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 Agency how to assess scientific data. Rather, it provided the Agency with guidelines for developing regulations once it had evaluated the evidence before it.
See , e.g. , Pearson I , 164 F.3d at 659 (“[W]here 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.”). This is not , however, to say that where the FDA’s conclusions are contrary to its purported evaluation standards or are otherwise arbitrary, as the court concluded they were in
Pearson II and Whitaker , a reviewing court should not overturn the Agency. Se e , e.g. , Int’l Fabricare Inst. v . EPA , 972 F.2d 384, 389 (D.C. Cir. 1992) (agency’s decision may be overturned where it has “failed to respond to specific challenges that are sufficiently central to its decision”); Ethyl Corp. v. EPA , 541 F.2d 1, 36 (D.C. Cir. 1976) (court has duty to give “close scrutiny” to technical evidence and to “hold[] agencies to certain minimal standards of rationality. ”). But “[t] he enforced education into the intricacies of the problem before the agency is not designed to enable the court to become a superagency that can supplant the agency’ s expert decision

- maker. To the contrary, the court must g ive due deference to the agency’ s ability to rely on its own developed expertise.” Id.
B. Regulation of Commercial Speech
Beca use the qualified selenium health claims are commercial speech, the FDA’s refusal to authorize them must be evaluated under the analytical framework established in Central Hudson , discussed by the D.C. Circuit in Pearson I , and elaborated upon by the Supre me Court20 in Western States

. Whitaker , 248 F. Supp. 2d. at 8; see also Pearson I , 164 F.3d at 655 (“Under Central Hudson , we are obliged to evaluate a government scheme to regulate potentially misleading commercial speech by applying a three

- part test.”). The Supreme Court has “rejected the ‘highly paternalistic’ view that government has complete power to suppress or regulate commercial speech.” Central Hudson , 447 U.S. at 562 (quoting Virginia Pharmacy Bd. v. Virginia Citizens Consumer Council , 425 U.S. 748, 770 (1976)). Moreover, it has distinguished between “inherently misleading” speech and “potentially misleading” speech. “[Actually or
i nherently m]isleading advertising may be prohibited entirely. ” In re R.M.J. , 455 U.S. 191, 203 (1982). “But t he States may not place an absolute prohibition on certain types of potentially misleading information . . . if the information also may be presented in a way that is not deceptive.” Id. Moreover , “[t]he First Amendment does not allow the FDA to si mply asse rt that [a plaintiff’s c ] laim is misleading in order to ‘supplant its burden to demonstrate that the harms it recites are real and that its restriction will in fact alleviate them to a material degree. ’ ” Whitaker , 248 F. Supp. at 9 (quoting Ibanez , 512 U. S. at 146). Indeed , in Pearson I , the D.C. Circuit rejected the FDA’s contention that health claims lacking “significant scientific agreement” are inherently misleading as “ almost frivolous. ” Pearson I , 164 F.3d at 655. Even when it finds “that speech i s misleading, the government must consider that ‘people will perceive their own best interests if only they are well enough informed, and . . . the best means to that end is to open the channels of communication rather than to close them.’” Whitaker , 248 F. Supp. 2d at 9 (quoting Virginia Pharmacy Bd. , 425 U.S. at 770 ). Central Hudson established a multi

- step analysis of speech regulation . “As a threshold matter,” the Court must determine “whether the commercial speech [being regulated] concerns unlawf ul activity or is misleading.” Western States , 535 U.S. at 367. If so, the speech is not21 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)). If it is, the Court then ascertains “whether the regulation [at issue] directly advances the governmental interest asserted” and “whether [the regulation] is not more extensive than is necessary to serve that interest.” Id. (quoting Central Hudson , 447 U.S. at 566.) This last step requires the Court to e valuate “whether the fit between the government’s ends and the means chosen to accomplish those ends is . . . reaso nable.” 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 Sta tes , 535 U.S. at 371 (quoting Central Hudson , 447 U.S. at 566). “ [ I ]f the
G overnment 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

n oted 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 (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).22 II. FD A’S COMPLETE BAN OF PLAINTIFFS’ CLAIMS In its response to plaintiffs’ petition, t he Agency denied four of the proffered claims outright. ( FDA Resp. at AR 001963, 001965, 001992

- 001993.) Under Central Hudson and
Pearson I , the FDA may refuse to consider disclaimers for health claims ( i.e. , prohibit their use completely) only if such health claims are inherently misleading , Whitaker , 248 F. Supp. at 9, or are potentially misleading but the Agency has deemed the claim “incurable by disclaimer.”
Pearson I , 164 F.3d at 659. The court in Whitaker arguably went even further than Pearson I , holding that “any complete ban of a claim would be approved only under narrow circumstances,
i.e. , when there was almost no qualitative evidence in support of the claim and where the government provided empirical evidence proving that the public would still be deceived even if the clai m was qualified by a disclaimer.” 21

21 The FDA argues that Whitaker “ strayed from Pearson I by suggesting that [the Agency] is req uired, under the First Amendment, to present empirical evidence about the misleading nature of a claim even where there is no evidence supporting the claim or the evidence in support of the claim is qualitatively weaker than the evidence against the claim. ” (Def s .’ Reply in Supp. of I ts Cross

- Mot. for Summ. J. and I n Opp’n to Pls.’ Mot. for Summ. J. [“Defs.’ Reply”] at 7.). Plaintiffs maintain that “no doctrinal or legal difference of any decisional significance between Pearson I and Whitaker ” exists. (P ls.’ Surreply to Defs.’ Reply in Supp. of Defs.’ Cross

- Mot. for Summ. J. and In Opp’n to Pls.’ Mot. for Summ. J. at 7.) Despite extensive debate, the Court need not decide whether Whitaker has improperly increased the government’s burden, because it concl udes that the FDA has not shown that there is no credible or only qualitatively weaker evidence in support of plaintiffs’ claims or that the claims are “incurable by disclaimer.” See Pearson I , 164 F.3d at 659. Whitaker , 248 F. Supp. 2d at 11 (emphasi s added) ; see also Pearson I , 164 F.3d at 659

- 60 ( suggesting that g overnment 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 decep tiveness”)

. The Court considers each of plaintiffs’ claim s to23 determine whether the FDA has met its burden with respect to those claims it has banned outright. 22

A. Plaintiffs’ “Certain Cancers” and “Anticarcinogenic Effects” Claim s The FDA asserts that cl aim s that selenium may reduc e the risk of certain cancers and may produce anticarcinogenic effects are “misleading on their face,” “ independent of the proffered scientific ev i dence.” (Defs.’ Mot. at 23.) Specifically, t he Agency concluded that the certai n cancers claim “is incomplete and misleading because it fails to reveal the individual cancer(s) that selenium may have an effect on,” thus leading a consumer to purchase selenium in hopes of preventing a cancer for which there is no evidence of risk redu ction from selenium intake. ( FDA Resp. at AR 001963.) The FDA also argues that by “referring in general terms to ‘certain cancers,’ the request ed claim language . . . suggests that cancers at different sites are essentially the same disease and that it is not important to distinguish between them.” ( Id. ) Similarly, the an ticarcinogenic effects claim “falsely implies that [selenium] can protect against all cancers,” when in fact cancer “is not a single disease” but a “collective term for a large number of individual diseases that differ with respect to risk factors, etiology, methods of

22 The Court considers only the first senten ce of each of plaintiffs’ proposed claims, not the suggested disclaimer in the second sentence ( i.e. , that the “[s]cient ific evidence supporting this claim is convincing but not yet conclusive” ). ( FDA Resp. at AR 001957

- 001958.) To the extent the FDA den ied these claims outright , it did so on the basis of the claimed relationship between selenium dietary supplements and various cancers, not because of the disclaimer. ( See , e.g. , Defs.’ Mot. at 23 (FDA concluded that certain cancers and anticarcinogenic e ffects claims were misleading “independent of the proffered scientific evidence”)). Specifically, w here the FDA banned a claim entirely because it found “no credible evidence of a risk reduction relationship” or believed the claim was inherently misleadin g, it concluded that the proposed disclaimer was “clearly false” without further assessment of its merits. ( FDA Resp. at AR 001993.) To the extent the Court overturns the Agency’s findings as to the substance of the health claims, it must allow the FDA t o consider plaintiffs’ proposed disclaimer and/or alternate disclaimers in the first instance. See , e.g. , Pearson I , 164 F.3d at 659 (“We do not presume to draft precise disclaimers for each of appellants’ . . . claims; we leave that task to the agency in the first instance.”).24 diagnosis and treatment, and mortality risk.” ( Id. at AR 001964; see also Def s .’ Mot. at 23.) Moreover, the Agency argues that the phrase “anticarcinogenic effects” is ambiguous because “anticarcinogenic” might mean both the “treatment and mitigation of existing cancer as well as the reduction of risk of getting cancer in the first place.” (Def.’s Mot. at 24.) Since “[c]laims about treatment or mitigation of disease ar e classified as drug claims, not health claims,” the FDA “believes that no qualified claim based on that phrase would be truthful and non

misleading.” ( FDA Resp. at AR 001965.)
T he Court concludes that the FDA ’s position fails under Pearson I

. T he Age ncy has not provided any empirical evidence, such as “studies” or “anecdotal evidence, ” that consumers would be misle d by either of plaintiffs’ claim s were they accompanied by qualifications

. See
Pearson I , 164 F.3d at 659 (government’s “conclusory assert ion” of misleadingness insufficient to meet burden); see also Edenfield v. Fane , 507 U.S. 761, 771 (1993) ( rejecting restriction of commercial speech where government “present[ed] no studies” and “record d[id] not disclose any anecdotal evidence . . . that validates the [government’s] suppositions” that unregulated speech would cause “fraud and overreaching”). Moreover, the explanation the FDA offers to demonstrate that plaintiffs’ claim s are misleading

— that the claims leave out pertinent information

— is no t support for banning the claim s entirely, but rather favors the approach of remedying any potential misleadingness by the disclosure of additional information. The FDA’s position is particularly troubling in light of its admission that plaintiffs’
certa in cancers claim “is literally true . . . in that there is credible evidence that selenium may reduce the risk of at least three cancers ” and that the anticarcinogenic effects claim “is true to the extent that it refers to reducing the risk of . . . three cancers[.]” ( Defs.’ Reply at 10 n.8.) As the Circuit Court in Pearson I made clear, “the government’s interest in preventing the use of labels25 that are true but do not mention [material information] would seem to be satisfied

- at least ordinarily

- by inclu sion of a prominent disclaimer setting forth [that information].” 164 F.3d at 659 (emphasis added). Here, the FDA has not provided any evidence that completing plaintiffs’ certain cancers claim by “reveal[ing] the individual cancer(s) that selenium may h ave an effect
on” and explaining that cancers at different sites are different diseases and respond different ly to treatments would not eliminate the consumer confusion it fears

. And , the FDA’s argument that “disclaimer language defining ‘anticarcinogenic ’ as reducing the risk of, rather than treating or mitigating, cancer would not cure the misleading nature” of the claim because it “would still fail to specify th e disease at issue” (Defs.’ Mot. at 27) begs the question why an additional disclaimer, speci fying the disease[s], would not remedy the purported problem. 23

23 In its reply, the FDA appears to answer this question by arguing that qualifying language would “merely add more information [to the certain cancers and anticarcinogenic effects claim s ] without solving the problem created by the inherently misleading language of the claim itself.” ( Defs.’ Reply at 11.) Specifically, it maintains that a disclaimer defining the phrase “anticarcinogenic effects” and specifying the cancers at issue would “undercut the claim and create confusion as to why the broad ‘anticarcinogenic effects’ statement appears on the product if the evidence only supports risk reduction for three cancers.” ( Id. at 11

- 12.) It then contends that appending qualifying language such as ‘specifically prostate, bladde r, and thyroid cancer’ to the ‘certain cancers’ claim to inform consumers of the cancers for which there is credible evidence of possible risk reduction would not be sufficient to prevent deception because the broader ‘certain cancers’ language would still incorrectly suggest a possible protective effect against other unnamed cancers, and the inconsistency between the broader language of the claim and the narrower language of the disclaimer would create confusion and uncertainty as to the scope of the claim ed benefit. (Defs.’ Reply at 12.) But these conclusory contentions are insufficient to meet the Agency’s burden under the commercial speech doctrine

. See Edenfield , 507 U.S. at 770

- 71 (government’s obligation to “demonstrate that the harms it recites are real and that its restriction will in fact alleviate them to a material degree” “is not satisfied by mere speculation or conjecture”). The Agency offers no support for its claim that limiting the type of “protective effect” and “risk26 Supreme Court precedent and Pearson I obligate the FDA to, at a minimum, consider “less restrictive” means of correcting that misleadingness before it turns to suppression. Pearson
I , 164 F.3d at 657

- 58; see also Bates , 433 U.S. at 374

- 75 (rejecting notion that “the public is better kept in ignorance than trusted with correct but incomplete information”). Because t he Agency has not done so here , the Court will remand the claims relating t o certain cancers and anticarcinogenic effects to the FDA for the purpose of drafting one or more disclaimers or, alternatively, setting forth empirical evidence that any disclaimer would f ail to correct the claim s ’ purported misleadingness.

reduction” claime d would insufficiently prevent consumers from assuming that selenium may also lower the risk of other cancers. It also fails to explain what “confusing contradiction” would result from such disclaime rs. On the contrary, it acknowledges that the claim s ar e true because of , not in spite of, evidence that selenium may reduce the risk of particular cancers. ( Defs.’ Reply at 10 n.8.) The FDA’s reliance on International Dairy Foods Association v. Boggs , No. 08

- 628, 2009 WL 937045, at *5 (S.D. Ohio Apr. 2, 20 09) , which involved a state regulation that prevented sellers of dairy products made from cows not treated with rbGH from advertisi ng their products as “rbGH free, ” is unavailing. There, the c ourt held that the phrase “rbGH free” was inherently misleading because it implied that there was a “compositional difference between those products that are produced with rbGH and those that are not,” when in fact no such difference exists. Id. at *6. The restricted claims in Boggs are different from plaintiffs’ cl aim s . The “rbGH free” claim, while literally true, sent a message

— that rbGH free milk is different from milk produced by cows given rbGH

— that was completely false. Here, by contrast, the FDA concedes that plaintiffs’ anticarcinogenic and certain cancers claims “contain a kernel of truth,” but are overly broad. (Defs.’ Reply at 10 n.8.) Yet, the FDA rejects disclaimers explicitly limiting the scope of plaintiffs’ proposed claim to those circumstances supported by credible evidence, arguing that such disc laimers would “defeat the purpose of making the claim[s] in the first place.” ( Id. at 12 (quoting Boggs , 2009 WL 937045, at *7).) The Court fails to see how limiting a claim so that it accurately reflects the evidence in support of the claim defeats the purpose of making the claim at all. Nor is this situati on analogous to United States v. Kasz Enterprises, Inc. , 855 F. Supp. 534, 542

- 43 (D.R.I. 1994), where the disclaimers at issue were clearly inconsistent with the message defendants sought to convey a nd therefore effectively served to undo the original claim s. S ee Pearson I , 164 F.3d at 659 (where evidence in support of claim is outweighed by evidence against it , disclaimer that “n o evidence supports this claim” would not cure claim’s misleadingness). Absent evidence that consumers are unable to read qualified versions of plaintiffs’ claims without assuming that selenium prevents diseases not stated by the claims, the FDA has not demonstrated that disclaimers would be ineffective and that suppression of these claims is thus warranted

.27 B. Plaintiffs’ L ung and Respiratory Tract Claim In contrast to the certain cancers and anticarcinogenic effects claims, the FDA considered the scientific evidence proffered by plaintiffs and concluded that it could draw scientific conclusions from only four of those stud ies concerning plaintiffs’ lung/respiratory tract claim. 24

As an initial matter, the FDA’s determination regarding the lung and respiratory tract claim is not inconsistent with Pearson I , in which the Court allowed for the possibility that “where evidence in support of a claim is outweighed by evidence against the claim, the FDA coul d deem it incurable by a disclaimer and ban it outright.” 164 F.3d at 65 9. Here, the Agency claims that there is no evidence in support of the proposed claim and cites studies suggesting that there is no relationship between selenium intake and reduced lung cancer risk . However, the Court in Pearson I also suggested that whe n “‘credible evidence’ supports a claim, that claim may not be absolutely prohibited.” Whitaker , 248 F. Supp. 2d at 10; see also Pearson I , 164 F.3d at 658

- 59 (where “credible evidence” supported a proposed claim, “a clarifying di sclaimer ( FDA Resp. at AR 001985.) Because all of those studies reported “no significant difference in mean serum levels” between control cases and lung cancer cases, the Agency concluded that “there is no credible evidence for a claim about selenium supplements and reduced risk of lung cancer or other respiratory tract cancers.” ( Id. at AR 001985, 001989.) Plaintiffs contend that a number of the studies discounted by the FDA provide sufficient credible e vidence of a positive relationship between selenium intake and a lowered risk of lung and respiratory tract cancers

. ( Pls.’ Mot. at 34

- 36; Pls.’ SMF ¶¶ 37

- 39.)

24 The only studies relied upon by the FDA for this claim concerned the relationship between selenium and lung cancer, as opposed to other respiratory tract cancers. ( FDA Resp. at AR 001985.)28 could be added” to note that the evidence was inconclusive). Therefore, the proper inquiry is what qualifies as “credible evidence ” and is there any such evidence to support the lung and respiratory tract claim? In its latest Guidance Document, the FDA states that it u ses an “evidence

- based review system” to evaluate the strength of the evidence in support of a statement. The process
involves a series of steps to assess scientific studies and other data, eliminate those from which no conclusions about the substance/d isease relationship can be drawn, rate the remaining studies for methodological quality and evaluate the strength of the totality of scie ntific evidence by considering study types, methodological quality, quantity of evidence for and against the claim (tak ing into account the numbers of various types of studies and study sample sizes), relevance to the U.S. population or target subgroup, replication of study results supporting the proposed claim, and overall consistency of the evidence. After assessing the totality of the scientific evidence, FDA determine s whether there is [significant scientific agreement] to support an authorized health claim, or credible evidence to support a qualified health claim. ( Guidance Document at AR 003512 (emphasis added) .) While t he document does not define “credible,” it does set forth threshold questions and categorizations the Agency uses to prioritize certain types of evidence over others. For example, it states that “ [ r ] andomized, controlled trials offer the best asse ssment of a causal relationship between a substance and a disease. ” ( Id. at AR 003513.) In contrast, “research synthesis studies” and “review articles” “do not provide sufficient information on the individual studies reviewed” to determine critical eleme nts of the studies and/or whether those elements were flawed. ( Id. at AR 003517.) 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 s tudies 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. ( Id. at AR 003518

- 003522.) If the FDA concludes that the elements of a29 study are flawed such that i t is impossible to draw scientific conclusions from the study, it eliminates that study from further review. ( Id. at AR 003518.) Using the above procedure, the FDA disregarded the studies plaintiffs cite as “credible evidence” in support of their propo sed lung/respiratory tract claim : the v an den Brandt et al. study; the Knekt et al. study; the Zhuo et al. review article ; and the “SU.VI.MAX” study

. 25 (Pls.’ Mot. at 34

- 36.) T he Agency states that it eliminated the v an den Brandt and Knekt studi es becau se they were conducted o n Dutch and Finnish populations whose average baselin e selenium levels (53.9 to 62.5 μg/L in blood and .5 μg/g in toenail clippings, respectively) are significantly lower than the levels observed in the “vast majority of the U.S. po pulation.” 26

25 Plaintiffs cite four st udies as “credible evidence” supporting the lung/respiratory tract claim that were improperly discounted by the FDA. (Pls.’ Mot. at 34

- 36.) However, plaintiffs maintain that this is not a “comprehensive list of articles” they submitted in support of this claim and urge the Court to review the Administrative Record for all such materials. ( Id. at 34 n. 47.) In reviewing the nearly 4,000

- page record, the Court encountered multiple articles that evaluated or discussed a possible relationship between seleniu m and lung cancer. But the Court is not in the position, nor is it the Court’s role, to independently assess whether these publications, many of which are highly technical and discuss interac tions at a bio

- molecular level ( see , e.g. , AR 001844 (Poerschke et al., Modulation of redox status in human lung cell lines by organoselenocompounds: Selenazolidines, selenomethionine, and methylseleninic acid , 22 Toxicology in Vitro 1761

- 1767 (2008)), constitute “credible evidence” in support of plaintiffs’ claim. As such, the Court will limit its consideration to the four articles relied on by plaintiffs to assess whether the Agency’s evaluation is inconsistent with the standards outlined in its current Guidance Document , irrational, and /or arbitrary and capricious. See Whitaker , 248 F. Supp. 2d at 11 (reviewing FDA’s evaluation of scientific evidence to ensure A gency conducted a “process of reasoned decision

- making” and that decision was not arbitrary and capricious ). ( FDA Resp. at AR 001979.) Indeed, it appears that the v an den Brandt and Knekt studies focused on populations who se members suffer from a selenium deficiency, since “nutritional adequacy of

26 By comparison, a ccording to a 2003 study, blood serum selenium concentrations in the U.S. population range from 91 μg/L (1 st percentile) to 168 μg/L (99 th percentile). ( FDA Resp. at AR 001977.) From this, the FDA concluded that “populations [ with ] blood selenium concentrations of less than 90 μg /L are not applicable to the general U.S. population.” ( Id. ) Similarly, studies from 1995 and 1998 indicate that toenail selenium concentration in the U.S. population is around .86 μg/g, with the lowest quintile ranging from .66 to .72 μg/g. ( Id. at AR 001978.)30 selenium is defined as the amount of selenium that is needed to saturate selenium enzyme activities; this occurs at blood selenium concentrations of 70

- 90 μg/L.” ( Id. at AR 001977.) Th e Agency’s elimination of the v an den Brandt and Knekt studies is thus consistent with the 2009 Guidance Document, which st ates that “[s]cientific conclusions cannot be drawn from studies conducted in countries or regions where inadequate intake of the substance is common since a response to the intake of the substance may be due to the correction of a nutrient deficiency for which health claims are not intended.” ( Guidance Document at AR 3521.) In fact, the Knekt study noted that “ the serum selenium level of the present population was about 60 percent of the levels generally observed in other Western countries ” and found onl y that “individuals with a low serum selenium concentration had an elevated risk of lung cancer .” (AR 00 15 69

- 001570.) The study further noted that “[h]igher serum selenium was associated with a reduced risk only at low alphatocopherol levels.” (AR 00157 0.) Similarly, the v an den Brandt found an inverse association between toenail selenium content and the risk of lung cancer, but it noted that selenium levels in the Netherlands are “intermediate between those reported from New Zealand and the United Stat es.” (AR 003170.) As such, the FDA’s decision not to extrapolate from these studies to the U.S. population is both rational based on the studies’ conclusions and consistent with the Agency’s evaluation criteria. The FDA contends that it eliminated t he Z h u o publication from its evaluation because the article “only reviewed lung cancer studies” and did not purport to provide “scientific evidence” in support of plaintiffs’ claim. (Defs.’ Mot. at 41.) Moreover, the Agency generally excludes such review art icles because they “‘do not contain sufficient information on the individual studies reviewed’ from which scientific conclusions can be drawn.” ( Id. (quoting FDA Resp. at AR 001968 ) .) Based on its review of the article, the Court concludes that the Agenc y’s decision31 to exclude t he article from its evaluation wa s not arbitrary and capricious. While t he article discusses 16 studies ( some of which are also included in the record), it is not apparent from the article that the Agency had sufficient informatio n from the Zhuo article to determine whether these studies contained design flaws. Moreover, many of the populations studied have low selenium levels that may not be the case in the U.S. population. (AR 003799

. ) Indeed, the article concludes that “[w] e found evidence that selenium could have protective effects; however, based on this analysis and other evidence, these effects apparently occur primarily in populations where overall selenium levels are low.” (AR 003803

. ) Th e FDA’s findings regarding the v an den Brandt and Knekt studies suggest that even had the Agency considered the Zhuo article as providing scientific evidence, that evidence is not sufficiently credible to support plaintiffs’ claim. Finally, the Agency rejected the SU.VI.MAX study be cause the study “did not confirm that all subjects were free of the cancers of interest prior to the intervention” and therefore may have involved subjects who already had cancer at the time the study began. ( FDA Resp. at AR 001971.) Because of this omis sion , the FDA stated that it could not draw scientific conclusions from the study. ( Id. ) However, the SU.VI.MAX study states that one of the criteria for participation in the study was “lack of disease likely to hinder active participation or threatened [sic] 5

- year survival.” (AR 001660.) The study participants were intermittently e xamined, and participants were asked to report any health events monthly. ( Id. ) Whenever a possible adverse event, including “cancer of any kind,” was reported from whatev er source, records were collected and included in study data. ( Id. ) T he Agency also appears to have overlooked a later report on the SU.VI.MAX study population concerning prostate cancer , which noted that three participants were excluded at the start of the study because they had prostate cancer, indicating32 that some sort of cancer screening process was conducted at the study’s outset . (AR 001669.) As such , the Agency’s stated reason for its disregard of the study is unsupported by the record

. And the FDA provided no response to the plaintiffs’ argument regarding the results of the study, namely that “in men, the incidence of respiratory cancers was reduced from 88 per 100,000 for the control group to 37 per 100,000 for the supplemented group,” while in women, the “incidence of respiratory tract cancers was reduced from 21 per 100,000 in the control group to only 12 per 100,000 in the supplemented group.” (Pls.’ Mot. at 31; AR 01665.) In sum, while the Court concludes that the Agency’s exclusion of t he v an den Brandt, Knekt, and Zhuo publications on the basis of its Guidance Document was not irrational or arbitrary and capricious, the exclusion of the SU.VI.MAX study on the basis that it did not screen participants for cancer is not supported by the r ecord

. To the extent that the FDA is concerned about possible limitations of the SU.VI.MAX study protocol and/or results , it must remedy such limitations with disclaimers. See Pearson I , 164 F.3d at 658 (suggesting disclaimer for antioxidant claim to add ress Agency’s concerns about study limitations). Accordingly , the Court remands the lung/respiratory tract claim to the Agency to determine an appropriate disclaimer in light of the SU.VI.MAX study

.
C. Plaintiffs’ Colon and Digestive Tract Claim As with the lung/respiratory tract claim, the FDA concluded that there is no credible evidence for a claim about selenium supplements and reduced risk of colon or other digestive tract cancers. ( FDA Resp. at AR 001989; Defs.’ Mot. at 43.) After eliminating vario us studies from which it determined no scientific conclusions could be drawn, including studies it relied upon in the evaluation of other of plaintiffs’ claims, the FDA reviewed three prospective observational studies that it found reported no significant relationship between selenium33 concentration and the risk o f colorectal cancer. ( FDA Resp. at AR 001983

- 001985 .) Plaintiffs challenge the FDA’s conclusions regarding one of these studies (the Peters et al. study) and cite additional publications they cont end were wrongly excluded from the FDA’s evaluation of their colon and digestive tract claim: the Clark et al. study; the Ghadirian et al. study; the Fernandez

Banares et al. study; the Jaskiewicz et al. study; the Das et al. review article; the Schrauzer et al. study; and the Wei et al. study

. (Pls.’ Mot. at 36

- 38.) In its response to plaintiffs’ petition, the Agency stated that the Peters study was of “high methodological quality” ( FDA Resp. at AR 001984), which is the highest ranking the FDA gives
to human intervention and observational studies, which in turn are the two types of studies the Agency considers most reliable. ( Id. at AR 001961; see also AR 003523

- 003526.) However, the Agency concluded that because “ [ t ] here was no significant difference i n the overall incidence of adenomatous colorectal polyps (a surrogate endpoint for colorectal cancer) between the five quintiles of serum selenium [levels],” the study did not provide evidence of a relationship between selenium and a reduced risk of colore ctal cancer. ( FDA Resp. at AR 001984.) Upon review of this study, the Court concludes that the FDA’s determination that this study does not constitute credible evidence in support of plaintiffs’ claim is unreasonable and unsupported by the findings of th e study . The study concluded that “ [o] verall, higher serum selenium levels were inversely associated with reduced risk of advanced colorectal adenoma.” (AR 002910.) In particular, the authors noted that men in “the highest quintile of selenium had 43% l ower risk for advanced colorectal adenoma compared with men in the lowest quintile.” (AR 002909.) The authors later state d that “[f]indings from our study [and another study] particularly support inverse association [between selenium and] advanced adenom a.” (AR 002912.) These findings

are squarely at odds with the FDA’s conclusion that the study showed no significant difference34 in adenomas across the various levels of selenium. Therefore , the Court finds that the Peters study was unreasonably discounte d as credible evidence. The Agency excluded several studies because they are “retrospective,” meaning that they measured selenium intake after the subjects “had already been diagnosed with the disease

. ” (Defs.’ Mot. at 43.) Because the health status of subjects can have an effect on selenium measurements, the FDA concluded that it could not determine whether the lowered selenium levels observed in these studies were caused by the cancer or by the participants’ nutrient intake. ( Id. ) The Court defers t o the FDA’s position with respect to retrospective studies generally and its determinations regarding the Clark, Fernandez

- Barnares, and Jasckiwicz studies , which appear reasonable and consistent with the Agency’s Guidance Document . However, the Agency’s explanation for exclusion is inapposite with respect to the Ghadrian study . There, the authors measured toenail selenium because it is “the best measure of assessing long

- term dietary selenium.” (AR 003844.) They then noted that in their study, “toenail selenium represents the dietary selenium intake prior to the diagnosis of cancer, as toenails were collected mainly before the final diagnosis or major treatment.” ( Id. (emphasis added). ) The study found a “significant inverse association . . . between toenail selenium levels and the risk of colon cancer.” (AR 003841.) The Court concludes that the FDA’s exclusion of this study from its evaluation of plaintiffs’ claim because it is retrospective was unreasonable, given the clear representations in the study as to the nature of the selenium intake observed

. T he FDA’s rejection of the Schrauzer, Das, and Wei publications is consistent with the Agency’s guidance, discussed previously, regarding review articles and studies of nutritionally

deficient populat ions

. However, it is difficult to discern the logic in the FDA’s decision to exclude from its evaluation of plaintiffs’ digestive tract claim studies the Agency relied on for35 scientific conclusions concerning other of plaintiffs’ claims ( e.g. , the Criqui et al. study; the Ringstad et al. study, and the Willet et al. study). ( FDA Resp. at AR 001983

- 001985.) Although the Criqui and Willet studies showed an inverse relationship between selenium and gastrointestinal cancer (AR 002248, 003278) , the FDA exclud ed them from consideration of plaintiffs’ claim because they do not include information about the site

- specific gastrointestinal cancers measured. ( FDA Resp. at AR 001983

- 001984.) “G astrointestinal” cancers are “digestive tract” cancers , at least accordi ng to the National Institutes of Health’s National Cancer Institute (NCI), on which the FDA relies heavily in defining and categorizing cancers. ( See id. at AR 001962 (“Cancer is categorized into different types based on specific organ and tissue sites (N ational Cancer Institute).”) NCI defines “digestive tract” as “ [t]he organs through which food and liquids pass when they are swallowed, digested, and eliminated. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum and anus.” 27 NCI’s definition of gastrointestinal (“ [ r ] efers to the stomach and intestines”) 28 thus suggests that gastrointestinal cancers are a subset of digestive tract cancers , meaning that a reduced risk of gastrointestinal cancers necessarily constitutes a reduced risk of digestive tract cancers

. Therefore , t he failure of the Criqui and Willet studies to specify the gastrointestinal cancers observed is irrelevant to whether they are credible evidence in support of plaintiffs’ claim. 29

27 National Cancer Institute, Dictionary of Cancer Terms, available at T he Cour t therefore finds that the FDA erred when it excluded these studies.

http://www.cancer.gov/dictionary/?CdrID=46447 (last visited May 26 , 2010).

28 National Cancer Institute, Dictionar y of Cancer Terms, available at http://www.cancer.gov/dictionary/?CdrID=45692 (last visited May 26 , 2010).

29 To the extent the Agency fears that consumers hoping to prevent a type of digestive tract cancer other than a gastrointestinal cancer will be misled by the claim, qualifying language can be used to limit the claim’s scope. See Pearson I , 164 F.3d at 659 (government’s interest in36 In sum, based on its examination of the scientific literature and the FDA’s r esponse to plaintiffs’ petition, the Court finds that the FDA’s decision to ban plaintiffs’ colon and digestive tract cl aim because there is no credible evidence in support of it “is unreasonable because it is not supported by a review of the available evidence or the FDA’s own Guidance Report.” See Whitaker , 248 F. Supp. 2d at 13. Indeed, it appears that credible eviden ce ( e.g. , the Peters, Ghadrian, Criqui, and Willet studies) does support this claim. As such, complete suppression of the claim is unwarranted. See Whitaker , 248 F. Supp. 2d at 10; see also Pearson I , 164 F.3d at
658

- 59; Pearson II , 130 F. Supp. 2d at 11 4. The Court will remand this claim to the Agency for reconsideration and , if needed, appropriate qualifying language.

III. FDA’S QUALIFICATION OF PLAINTIFFS’ PROSTATE CLAIM After reviewing the scientific literature submitted with plaintiffs’ petition, the F DA concluded that it could draw scientific conclusions regarding plaintiffs’ prostate claim from eight observational studies and one intervention study. ( FDA Resp. at AR 001989 .) Of these, the Agency determined that t wo nested case

- control studies sugges ted that selenium may reduce the risk of prostate cancer. ( Id. at AR 0 01989

- 001990 .) However, the FDA rejected plaintiffs’ proposed claim because it found the characterization of the evidence in support of the claim as “convincing but not yet conclusive” to be false and misleading. ( Id. at AR 001993.) Instead , the Agency stated that it would exercise enforcement discretion with respect to the following qualified health claim : “Two weak studies suggest that selenium intake may reduce the risk of prostat e cancer. However, four stronger studies and three weak studies showed no reduction in

preventing labels that do not include material information “would seem to be satisfied

- at least ordinarily

- by inclusion of a prominent disclaimer”).37 risk. Based on these studies, FDA concludes that it is highly unlikely that selenium supplements reduce the risk of prostate cancer.” ( Id. ) The Court agrees with p laintiffs’ 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. See Pearson I , 164 F.3d at 656 n.5 (quotin g State University of New York v. Fox , 492 U.S. 469, 480 (1989)). The Agency has not drafted a “precise disclaimer” designed to qualify plaintiffs’ claim while adhering to the “First Amendment preference for disclosure over suppression, ” as mandated

. Pea rson I , 164 F.3d at
658

- 59. Rather, it has replaced plaintiffs’ claim entirely

. And the Agency’s “ qualification ” effectively negates any relationship between prostate cancer risk and selenium intake. Indeed, the FDA’s language is an example of a “discla imer” that “contradict [s] the claim and defeat s the purpose of making [it] in the first place .” (Defs. ’ Reply at 11 .) While such language might be appropriate were there no credible evidence in support of a positive relationship between prostate

cancer r isk and selenium intake , the Agency concedes that there is such evidence. ( FDA Resp. at AR 001986 , 001990 .) As such, the FDA is obligated to at least consider the possibility of approving plaintiffs’ proposed language with the addition of “short, succinc t, and accurate disclaimers

. ” Pearson II , 130 F. Supp. 2d at 120. Here, the FDA has completely eviscerated plaintiffs’ claim, with no explanation as to why a less restrictive approach would not be effective. For instance, t o the extent that the FDA take s issue with the proposed “convincing but not yet conclusive” claim, the Agency makes no attempt to demonstrate that this concern would not be accommodated by altering this portion of the claim with language that more accurately reflects the strength of th e scientific evidence at issue

. Such qualification would be a “far less restrictive means” than negation of plaintiffs’ claim. Pearson I , 164 F.3d at 658.38 Moreover, in light of its review of the scientific literature, the Court finds that the Agency’s “d isclaimer” is inaccurate. For example, the FDA concluded that the Li et al. study showed “no significant difference in plasma selenium levels between cancer

- free controls . . . and prostate cancer cases” and “no significant relationship between plasma sel enium levels and prostate cancer risk.” ( FDA Resp. at AR 001986.) Yet , the studies’ authors stated that they “found a statistically significant inverse association between pre

- diagnostic plasma selenium levels and the risk of advanced prostate cancer.” (AR 001697.) Further, among men with “increased PSA levels at baseline,” the authors found that “higher levels of selenium were associated with a reduced risk of all prostate cancer.” ( Id. ) The FDA argues that the Li study does not support plaintiffs’ c laim because the statistically significant relationship between selenium and cancer risk appeared only when the investigators “stratified the subjects into five groups based on the pre

- diagnostic plasma selenium levels and compared the highest group to the lowest.” (Defs.’ Mot. at 38.) Yet, the purported absence of a significant difference in cancer risk “between the five quintiles of serum selenium” was the very reason the Agency excluded a study in the evaluation of plaintiffs’ colon and digestive tract claim. ( FDA Resp. at AR 001984.) Such inconsistency is unreasonable. Even if the FDA determines the study evidences only a limited reduction in risk in certain subgroups (Defs.’ Mot. at 38), the Court concludes that the Agency erred in finding that the study “show[s] no reduction in [prostate cancer] risk.” In short, the FDA’s replacement of plaintiffs’ claim with different and contradictory language is inconsistent with the spirit, if not the letter, of Pearson I

. The FDA has failed to justify the c omplete substitution of new language for plaintiffs’ proposed claim, especially since it appears that the Agency’s central objection to the claim concerns the nature of the qualifying language, not the underlying relationship claim. Additionally, although the Court has not39 conducted a complete review of the Agency’s analysis of the scientific evidence subm itted in support of this claim, 30 the Agency’s replacement claim mischaracterizes at least one study (Li et al) , suggesting that the FDA’s proposed claim is inaccurate. As such, the Court will remand plaintiffs’ prostate claim to the FDA for the purpose of reconsidering the scientific literature and drafting one or more short, succinct, and accurate disclaimers in light of that review

.
CONCLUSION Pla intiffs’ motion for summary judgment is granted in part and denied in part, and defendants’ cross

- motion for summary judgment is denied. This case is remanded to the FDA for the purpose of 1) dr afting one or more disclaimers to accompany plaintiffs’ certa in cancers, anticarcinogenic, and prostate claims, or, alternatively, setting forth empirical evidence that any disclaimer would fail to correct the claims’ purported misleadingness; 2) determining a n appropriate disclaimer to accompany plaintiffs’ lung an d respiratory tract claim in light of the SU.VI.MAX study ; and 3) reevaluating plaintiffs’ colon and digestive tract claim and drafting one or more disclaimers. The Court denies plaintiffs’ motion to the extent it seeks an order enjoining the FDA from pre cluding plaintiffs from placing their proposed health claims on dietary supplement labeling. (Pls.’ Mot. at 43.) It is not for this Court to pass judgment on the validity of plaintiffs’ proposed qualifying language in the first instance, see Pearson I , 1 64 F.3d at 659, nor can the Court rule out the possibility that “the government could demonstrate with empirical evidence that disclaimers . . . would bewilder consumers and fail to correct for deceptiveness.” Id. at 659

- 60. To that end, the Court remand s the claims at issue to the Agency for further review and

30 Because the Court remands this claim to the FDA on the basis of the Agency’s complete substitution of plaintiffs’ proposed claim, it did not need to review all o f the studies excluded or relied on by the FDA in evaluating plaintiffs’ claim.40 action consistent with this Memorandum Opinion. Although the Court is limited in its ability to mandate that the Agency act by a specific date, see Consumer Fed’n of Am. and Pub. Citizen v. United States Dep’t of Health and Human Servs. , 83 F.3d 1497, 1506

- 07 (D.C. Cir. 1996) , the Court expects that the FDA will act with reasonable speed in reviewing the proposed claims and drafting disclaimer language. See Whitaker , 248 F. Supp. 2d at 17 n.20.

/s/ ELLEN SEGAL HUVELLE United States District Judge DATE: May 27 , 2010