FAY, Circuit Judge:

Marianne and Daniel Chapman appeal summary judgment for The Proctor & Gamble Distributing, LLC and The Proctor & Gamble Manufacturing Company (collectively "P & G") in their products liability case concerning Fixodent, a denture adhesive. We affirm.

I. FACTUAL AND PROCEDURAL BACKGROUND

Marianne Chapman suffers from myelopathy, a neurological condition or spinal-cord disorder that affects the upper and lower extremities. She developed a number of neurological symptoms from April 2006 through January 2009.1 The Chapmans maintain Marianne Chapman's symptoms were caused by zinc-induced, copper-deficiency myelopathy ("CDM") from her use of two to four 68-gram tubes of Fixodent denture adhesive each week for eight years. P & G counters that the testimony of the Chapmans' experts should not be admitted, because their methodologies are unreliable and do not substantiate the conclusion that Fixodent caused Marianne Chapman's CDM.

While zinc is an essential element for human growth, it is not found separately in nature but occurs in various compounds, such as zinc acetate and zinc sulfate. In 1990, P & G reformulated Fixodent to include a calcium-zinc compound to improve its adhesion. The calcium-zinc compound in Fixodent is less bioavailable than other zinc compounds, like zinc acetate.2 A case report in 2008 hypothesized zinc in denture adhesives may lead to copper deficiency, which could cause neurologic injury. S.P. Nations, et al., Denture Cream: An Unusual Source of Excess Zinc, Leading to Hypocupremia and Neurologic Disease, 71 Neurology 639 (2008). Thereafter, various individuals filed lawsuits nationwide against GlaxoSmithKline ("GSK"), manufacturer of Poligrip, and P & G, manufacturer of Fixodent.

The Chapmans originally filed their case in Florida state court on April 1, 2009, against P & G, which removed it to federal court in the Southern District of Florida on diversity jurisdiction.3 On June 9, 2009, the United States Judicial Panel on Multidistrict Litigation ("MDL") transferred these similar cases against GSK and P & G to Judge Cecilia M. Altonaga in the Southern District of Florida for coordinated pretrial proceedings. In re Denture Cream Prods. Liab. Litig., No. 09-2051-MD-Altonaga. Following the conclusion of pretrial proceedings, the individual MDL plaintiffs had the right to transfer their cases back to their respective district courts. Because this case was the only one filed in the Southern District of Florida, it provided the judge with jurisdiction to proceed to trial.

The Chapmans sought to prove causation primarily through four expert witnesses.4 Dr. George J. Brewer, Dr. Joseph R. Landolph, and Dr. Ebbing Lautenbach would have testified generally whether Fixodent could cause CDM. Dr. Steven A. Greenberg would have testified Marianne Chapman's myelopathy specifically was caused by her use of Fixodent. P & G moved to exclude the Chapmans' expert testimony under Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993). Briefing, supplemental briefing, and a hearing addressed the issues raised by P & G's motions. On June 13, 2011, one week before trial was to begin on June 20, 2011, the district judge issued a comprehensive order granting P & G's motions to exclude the Chapmans' expert testimony. In re Denture Cream Prods. Liab. Litig., 795 F.Supp.2d 1345 (S.D.Fla.2011).

A. First Appeal

1. District Court

At the previously scheduled calendar call on June 14, 2011, the parties discussed with the judge the best route to this court to decide whether the judge's Daubert order was correct — interlocutory appeal or summary judgment. P & G argued the other MDL cases should be "stayed pending the appeals," because "it would make no sense for the parties to be litigating anything in those cases while the issues that are set forth squarely in the Court's order yesterday are addressed by the 11th Circuit." Hr'g Tr., June 14, 2011, at 6:3-10. The judge commented it would be "futile" and "a waste of everyone's resources" to have full briefing on summary judgment "just so [the parties] could get to the 11th Circuit on the correctness of [her] decision on the Daubert motions." Id. at 7:8-12. Instead, the judge suggested the parties "consent to an entry of judgment with the right to appeal the adverse Daubert ruling." Id. at 7:13-14.

On June 16, 2011, the judge held a scheduling conference to discuss further the proper way to get her Daubert decision before this court. The judge recognized "the problem is how do you get [the Daubert order] to the Appellate Court [because] you can't ... appeal ... a Daubert ruling. You need a final order." Hr'g Tr., June 16, 2011, at 6:21-23. She suggested "the way to do it is to have me enter judgment against [the Chapmans] with the understanding of the parties that you are reserving your right to appeal ... my adverse ruling on Daubert, but you need a final order." Id. at 7:5-8. Since both parties wanted the Daubert order reviewed by this court, the judge ordered the parties to "present to [her] a proposed order that contemplates" an appealable final judgment. Id. at 9:10-13.

On June 23, 2011, the parties submitted a Joint Stipulation of Dismissal with Prejudice, agreeing to "1) the entry of judgment against [the Chapmans] on all claims alleged against [P & G]; and, 2) the entry of dismissal with prejudice on all [the Chapmans'] claims alleged against [P & G]." Jt. Stip. of Dismissal at 1-2. The joint stipulation provided "the parties recognize that this stipulation is in the best interest of all parties and judicial economy" and expressly reserved the Chapmans' right to appeal to this court. Id. at 2. In accordance with the joint stipulation, the judge entered final judgment on June 24, 2011, and the Chapmans timely appealed.

2. Court of Appeals

This court recognized "our jurisdiction `must be both (1) authorized by statute and (2) within constitutional limits.'" Chapman v. Proctor & Gamble Distrib., LLC, No. 11-13371 at 2 (11th Cir. Jan. 4, 2012) (per curiam) (quoting OFS Fitel, LLC v. Epstein, Becker & Green, P.C., 549 F.3d 1344, 1355 (11th Cir.2008)). While the district judge's order was final under 28 U.S.C. § 1291, "to be within constitutional limits," it had to be "`adverse as to the final judgment' ... to satisfy the Article III case or controversy requirement." Id. (quoting OFS Fitel, 549 F.3d at 1356). We noted "three `distinct factual ingredients that are critical to the adverseness issue.'" Id. (quoting OFS Fitel, 549 F.3d at 1357). Those factual requirements are: (1) the appealed order was "`case-dispositive because it foreclosed plaintiff from presenting the expert testimony required to prove [the cause of action], which was a core element in all of its claims,'" (2) "plaintiff's attorney `candidly informed the district court of the impact of its sanctions ruling on the plaintiff's case,'" and (3) "`importantly, the district court ... agreed with plaintiff's counsel's suggestion that the [appealed] ruling was case-dispositive.'" Id. (alterations omitted) (quoting OFS Fitel, 549 F.3d at 1357, 1358).

We concluded the Chapmans did not meet the second and third OFS Fitel requirements. Although the parties had informed the district judge her Daubert order might be dispositive, the Chapmans "also argued that they could still muster enough evidence to prove causation at trial even without the expert testimony, specifically by presenting testimony from treating doctors." Id. at 3. Not only did the Chapmans fail "`candidly'" to inform the judge of the consequence of the Daubert order, but also they "disputed that it was dispositive." Id. (quoting OFS Fitel, 549 F.3d at 1357). Regarding the third requirement, we determined the district judge's dismissal was not case-dispositive. It was unclear whether the interlocutory appeal from the Daubert order excluding the Chapmans' expert witnesses was "the only basis for dismissal, or if the Chapmans could otherwise have proceeded to trial and proved causation despite the exclusion, as they initially conte[nd]ed." Id. at 3-4. In addition, the Chapmans' representation that it was undisputed that the Daubert order was case-dispositive was belied by their persistently "claiming that the order was not case-dispositive." Id. at 4. Accordingly, we dismissed the appeal of the Daubert order for lack of standing, because the Chapmans were not adverse to the final judgment. Id.

B. Second Appeal

Following dismissal of the Chapmans' first appeal by this court, the district judge granted their motion to vacate the stipulated final judgment under Federal Rule of Civil Procedure 60(b). P & G then moved for summary judgment, which the Chapmans opposed, and P & G replied. Because the district judge had determined none of the Chapmans' proffered experts qualified as experts under Daubert, P & G maintained the Chapmans could not use treating physicians as experts at trial. Since these doctors had never been designated as experts, the judge determined they were not qualified to testify regarding general or specific causation of Marianne Chapman's CDM. Accordingly, she granted P & G's summary judgment motion and entered final judgment. The Chapmans appealed, which is the case we now decide. We necessarily first must address the merits of the district judge's Daubert order, because it is incorporated by reference in the Chapmans' opposition to P & G's summary judgment motion,5 and the parties' first appeal to this court was dismissed for lack of jurisdiction without addressing the merits of the Daubert order.

II. DISCUSSION

A. Daubert Analysis

1. Distinguishing Daubert-Applicable Cases

For analyzing cases involving alleged toxic substances, we have delineated two categories. McClain v. Metabolife Int'l, Inc., 401 F.3d 1233, 1239 (11th Cir. 2005). The first category consists of "cases in which the medical community generally recognizes the toxicity of the [substance] at issue" to "caus[e] the injury plaintiff alleges." Id.; Hendrix ex rel. G.P. v. Evenflo Co., 609 F.3d 1183, 1196 (11th Cir.2010). In this category are "toxins like asbestos, which causes asbestosis and mesothelioma; silica, which causes silicosis; and cigarette smoke, which causes cancer." McClain, 401 F.3d at 1239. For judicial economy, federal courts need not consider expert opinions for diagnoses "medical doctors routinely and widely recognize as true, like cigarette smoking causes lung cancer and heart disease, too much alcohol causes cirrhosis of the liver, and ... the ingestion of sufficient amounts of arsenic causes death." Id. at 1239 n. 5. In cases where the cause and effect or resulting diagnosis has been proved and accepted by the medical community, federal judges "need not undertake an extensive Daubert analysis on the general toxicity question."6 Id. at 1239.

In contrast, the second category contains cases, where the medical community generally does not recognize the substance in question as being toxic and having caused plaintiff's alleged injury. Id. These cases require a two-part Daubert analysis, comprised of (1) general causation, "whether the [substance] can cause the harm plaintiff alleges," id., and (2) specific causation, whether experts' methodology determines the substance "caused the plaintiff's specific injury," Hendrix, 609 F.3d at 1196 (citing McClain, 401 F.3d at 1239). For cases in category two, a district judge "must assess the reliability of the expert's opinion on general, as well as specific, causation." Id. (first emphasis added). The two categories economize the time of a trial judge, who "does not need to waste time with a Daubert hearing `where the reliability of an expert's methods is properly taken for granted, and to require appropriate proceedings in the less usual or more complex cases where cause for questioning the expert's reliability arises,'" McClain, 401 F.3d at 1239 n. 5 (quoting Kumho Tire Co. v. Carmichael, 526 U.S. 137, 152, 119 S.Ct. 1167, 1176, 143 L.Ed.2d 238 (1999)).

The Chapmans represent the district judge should have analyzed this case under McClain category one, because there is a general consensus in the medical community that ingestion of zinc causes CDM. They cite medical textbooks and journals as well as their experts7 and those of P & G, who have recognized an association between excess zinc and copper deficiency. See Rider v. Sandoz Pharm. Corp., 295 F.3d 1194, 1199 (11th Cir.2002) ("[W]hile they may support other proof of causation, case reports alone ordinarily cannot prove causation."). But they fail to show that the zinc compound in Fixodent is in McClain category one of medically accepted, cause-and-effect toxins, such as asbestos causing asbestosis and cigarette smoking causing lung cancer and heart disease. Id. at 1239 & n. 5. P & G notes: "Millions of consumers have regularly used Fixodent for decades without complaint. Nevertheless, [the Chapmans] claim that Fixodent is toxic because it contains zinc in a calcium-zinc compound — even though zinc is undeniably an essential nutrient the body must have to function properly." Appellees' Br. at 1; see Guinn v. AstraZeneca Pharm. LP, 602 F.3d 1245, 1257 (11th Cir.2010) (per curiam) (recognizing in a products liability case that two-thirds of patients who took an antipsychotic prescription drug, Seroquel, did not experience weight gain, which plaintiff alleged was the cause of her diabetes). Therefore, the district judge properly determined that Fixodent, containing zinc, was in McClain category two and conducted the requisite Daubert review of proffered expert testimony, which included a thorough hearing and consideration of "thousands of pages of filings by the parties, including the experts' reports and depositions, and scientific literature." In re Denture Cream Prods. Liab. Litig., 795 F.Supp.2d at 1348.

2. Daubert Review for Reliability of Expert Testimony

Under Federal Rule of Evidence 702, expert testimony is admissible if (1) the expert is qualified to testify regarding the subject of the testimony; (2) the expert's methodology is "sufficiently reliable as determined by the sort of inquiry mandated in Daubert"; and (3) the expert's testimony will assist the trier of fact in understanding the evidence or determining a fact at issue. United States v. Frazier, 387 F.3d 1244, 1260 (11th Cir. 2004) (en banc) (citation and internal quotation marks omitted). In considering the proffered expert testimony, a trial judge is mindful "[t]he burden of establishing qualification, reliability, and helpfulness rests on the proponent of the expert opinion." Id. To determine the reliability and relevance of proffered expert testimony, the judge performs a "gatekeeping" function. Daubert, 509 U.S. at 589 n. 7, 113 S.Ct. at 2795 n. 7; see Quiet Tech. DC-8, Inc. v. Hurel-Dubois UK Ltd., 326 F.3d 1333, 1342 (11th Cir.2003) (recognizing "one may be considered an expert but still offer unreliable testimony"). We review a district judge's exclusion of expert testimony only for abuse of discretion. Gen. Elec. Co. v. Joiner, 522 U.S. 136, 141-43, 118 S.Ct. 512, 517, 139 L.Ed.2d 508 (1997). This "considerable leeway" accorded to the district judge, Kumho Tire Co., 526 U.S. at 152, 119 S.Ct. at 1176, requires us to defer to the judge's decision on expert testimony, "unless it is manifestly erroneous." Rink v. Cheminova, Inc., 400 F.3d 1286, 1291 (11th Cir.2005) (citation and internal quotation marks omitted). This deferential abuse-of-discretion standard is applied stringently, even if a decision on expert testimony is "outcome determinative."8 Gen. Elec. Co., 522 U.S. at 142-43, 118 S.Ct. at 517; United States v. Brown, 415 F.3d 1257, 1266 (11th Cir.2005).

The Daubert Court identified four factors to guide district judges in assessing the reliability of an individual expert's methodology:

United Fire & Cas. Co. v. Whirlpool Corp., 704 F.3d 1338, 1341 (11th Cir.2013) (per curiam) (citing Daubert, 509 U.S. at 593-94, 113 S.Ct. at 2796-97). These factors are not "a definitive checklist or test," Daubert, 509 U.S. at 593, 113 S.Ct. at 2796, and Daubert considerations are "applied in case-specific evidentiary circumstances," Brown, 415 F.3d at 1266. "[T]he trial judge must have considerable leeway in deciding in a particular case how to go about determining whether particular expert testimony is reliable." Kumho Tire Co., 526 U.S. at 152, 119 S.Ct. at 1176.

While the inquiry is "a flexible one," the focus "must be solely on principles and methodology, not on the conclusions that they generate." Daubert, 509 U.S. at 594-95, 113 S.Ct. at 2797 (emphasis added); see McDowell v. Brown, 392 F.3d 1283, 1298 (11th Cir.2004) (recognizing a trial judge "should meticulously focus on the expert's principles and methodology, and not on the conclusions that they generate"). "But conclusions and methodology are not entirely distinct from one another"; neither Daubert nor Federal Rule of Evidence 702 requires a trial judge "to admit opinion evidence that is connected to existing data only by the ipse dixit of the expert." Gen. Elec. Co., 522 U.S. at 146, 118 S.Ct. at 519. Instead, the judge "is free to `conclude that there is simply too great an analytical gap between the data and the opinion proffered.'" Hendrix, 609 F.3d at 1194 (quoting Gen. Elec. Co., 522 U.S. at 146, 118 S.Ct. at 519); see McDowell, 392 F.3d at 1299 (noting "there is no fit where a large analytical leap must be made between the facts and the opinion," such as proffering animal studies concerning a type of cancer in mice to establish a different cancer in humans (citing Gen. Elec. Co., 522 U.S. at 146, 118 S.Ct. at 519)). The district judge has "the task of ensuring that an expert's testimony both rests on a reliable foundation and is relevant to the task at hand." Daubert, 509 U.S. at 597, 113 S.Ct. at 2799.

As gatekeeper for the expert evidence presented to the jury, the judge "must do a preliminary assessment of whether the reasoning or methodology underlying the testimony is scientifically valid and of whether that reasoning or methodology properly can be applied to the facts in issue." Kilpatrick v. Breg, Inc., 613 F.3d 1329, 1335 (11th Cir.2010) (citation and internal quotation marks omitted). It is "proper" and "necessary" for the trial judge "to focus on the reliability" of a proffered expert's "sources and methods." Id. at 1336. Under Daubert, the "district judge asked to admit scientific evidence must determine whether the evidence is genuinely scientific, as distinct from being unscientific speculation offered by a genuine scientist." Allison v. McGhan Med. Corp., 184 F.3d 1300, 1316-17 (11th Cir. 1999) (citation and internal quotation marks omitted).

a. General Causation

General causation refers to the "general issue of whether a substance has the potential to cause the plaintiff's injury." Guinn, 602 F.3d at 1248 n. 1. The district judge consolidated her consideration of the proffered testimonies of Dr. Brewer, Dr. Landolph, and Dr. Lautenbach regarding general causation. Neither the judge nor the parties questioned that these three experts were qualified to testify based on their credentials, the first part of the Rule 702 test for admission of expert testimony. Frazier, 387 F.3d at 1260. The judge, however, determined that their methodologies were not sufficiently reliable to satisfy part two of the test and therefore would not assist the trier of fact in understanding the evidence, part three of the test. Id. We must review the judge's analysis that caused her to reach that conclusion.

At the outset, the judge placed this case in McClain category two, where "the medical community does not generally recognize the agent as both toxic and causing the injury plaintiff alleges." McClain, 401 F.3d at 1239. To establish generally "Fixodent is capable of causing a myelopathy," the Chapmans proffered the testimonies of three experts. In re Denture Cream Prods. Liab. Litig., 795 F.Supp.2d at 1350. "Dr. Brewer would testify `that zinc containing Fixodent denture adhesives are a health hazard and capable of causing severe hematological and neurological injury.'" Id. at 1350-51 (quoting Brewer Report). "Dr. Landolph would testify `that long-term use of Fixodent (containing 1.69% zinc) will result in ... neurotoxic, neurologic, and hematologic consequences.'" Id. at 1351 (quoting Landolph Report). Dr. Lautenbach would testify "that there is `an association between Fixodent and myeloneuropathy' and he would `consider the myeloneuropathy as a "probable" reaction related to denture adhesive use.'" Id. (quoting Lautenbach Report).

The judge reviewed reliable methodologies, including dose-response relationship, epidemiological evidence, background risk of the disease, physiological processes involved, and clinical studies. Id. at 1351-57. The judge determined the Chapmans' experts did not satisfy any of these recognized methodologies. Failure to satisfy any of the four reliability factors recognized in Daubert is sufficient to preclude the testimony of any of the general causation experts from testifying at trial. 509 U.S. at 593-94, 113 S.Ct. at 2796-97. Recognizing all substances potentially can be toxic, the judge noted "`the relationship between dose and effect (dose-response relationship) is the hallmark of basic toxicology,'" and "`is the single most important factor to consider in evaluating whether an alleged exposure caused a specific adverse effect.'"9 In re Denture Cream Prods. Liab. Litig., 795 F.Supp.2d at 1351-52 (quoting McClain, 401 F.3d at 1242). The judge noted, however, neither the Chapmans' general-causation experts "nor the articles on which they rely determine how much Fixodent must be used for how long to increase the risk of a copper-deficiency, or for how long a copper-deficiency must persist before an individual is at an increased risk of developing a myelopathy." Id. at 1352. Similarly, the judge recognized "[e]pidemiology is the `best evidence of causation'" in cases involving toxic substances. Id. at 1354 (quoting Kilpatrick, 613 F.3d at 1337 n. 8). But she determined the Chapmans' "experts have no analytical epidemiological evidence on which to base their inference of causation."10 Id.

The judge further noted "[b]ackground risk of disease `is the risk a plaintiff and other members of the general public have of suffering the disease or injury that plaintiff alleges without exposure to the drug or chemical in question.'" Id. at 1355 (quoting McClain, 401 F.3d at 1243). While "`[a] reliable methodology should take into account the background risk,'" the judge found the Chapmans' "causation experts uniformly testified that they did not know the background risk of copper-deficiency myelopathy," which was "a serious methodological deficiency."11 Id. (alteration in original) (quoting McClain, 401 F.3d at 1243). The judge explained:

Id. at 1356. The judge concluded the absence of background risk of disease was "a substantial weakness" in the Chapmans' experts' general-causation reasoning. Id.

Given the deposition admissions of Dr. Brewer, Dr. Lautenbach, and Dr. Landolph regarding their lack of knowledge of dose-response, epidemiological evidence, and background risk of disease, methodologies this circuit has recognized as indispensable to proving the effect of an ingested substance, we conclude that the testimonies of these proffered experts could not establish general causation of myelopathy by Fixodent. Because these experts have failed to demonstrate the primary methods for proving the zinc in Fixodent causes myelopathy, their secondary methodologies, including plausible explanations, generalized case reports, hypotheses, and animal studies are insufficient proof of general causation. This latter evidence could mislead the jury by causing it to consider testimony that was insufficient by recognized primary methodologies to prove using Fixodent causes myelopathy. As gatekeeper for the evidence presented to the jury, the judge did not abuse her discretion or commit manifest injustice by precluding the testimonies of Dr. Brewer, Dr. Lautenbach, and Dr. Landolph as experts on general causation.

b. Specific Causation

"Specific causation refers to the issue of whether the plaintiff has demonstrated that the substance actually caused injury in her particular case." Guinn, 602 F.3d at 1248 n. 1. The Chapmans proffered only one expert to prove specific causation, Dr. Greenberg, who would testify at trial: "`[A] diagnosis of copper deficiency myelopathy is certain... [and] in this patient, it was precisely the ingested zinc in the denture cream that caused her copper deficiency.'" In re Denture Cream Prods. Liab. Litig., 795 F.Supp.2d at 1365 (alterations and ellipsis in original) (quoting Greenberg Report). His conclusion allegedly resulted from "the scientifically accepted methodology of differential diagnosis," Guinn, 602 F.3d at 1253, "a medical process of elimination whereby the possible causes of a condition are considered and ruled out one-by-one, leaving only one cause remaining," Hendrix, 609 F.3d at 1195. Differential diagnosis includes three steps: (1) the patient's condition is diagnosed, (2) all potential causes of the ailment are considered, and (3) differential etiology is determined by systematically eliminating the possible causes. McClain, 401 F.3d at 1252. A reliable differential analysis "need not rule out all possible alternative causes," but "it must at least consider other factors that could have been the sole cause of the plaintiff's injury." Guinn, 602 F.3d at 1253. Differential diagnosis, "however, will not usually overcome the fundamental failure of laying a scientific groundwork for the general toxicity of the drug and that it can cause the harm a plaintiff suffered." McClain, 401 F.3d at 1252.

While differential diagnosis as a scientifically accepted methodology meets the Daubert guiding factors for district judges in deciding reliability, 509 U.S. at 593-94, 113 S.Ct. at 2796-97, Dr. Greenberg did not follow it. Marianne Chapman's treating physicians had not diagnosed her with CDM or informed her that her Fixodent use caused her neurologic symptoms.12 Although her diagnosis generally was "neurological syndrome," she was not professionally diagnosed with CDM until Dr. Greenberg examined her in the course of this litigation as the Chapmans' specific-causation expert.13 Greenberg Report at 10.

Marianne Chapman's medical history included neurological ailments that occurred before and after her Fixodent use.14 Notably, her neurological symptoms continued after she ceased using Fixodent.15 "Temporal proximity is generally not a reliable indicator of a causal relationship." Guinn, 602 F.3d at 1254. "The temporal connection between exposure to chemicals and an onset of symptoms, standing alone, is entitled to little weight in determining causation." McClain, 401 F.3d at 1254 (citation, internal quotation marks, and alteration omitted). But Dr. Greenberg failed to explore fully other potential causes of Marianne Chapman's CDM, which he diagnosed in the course of this litigation. In re Denture Cream Prods. Liab. Litig., 795 F.Supp.2d at 1366. In addition to copper deficiency as the cause of Marianne Chapman's neurological ailments, Dr. Greenberg had identified "structural spinal cord injury, multiple sclerosis, and vitamin B12 deficiency."16 Id. Given her extensive medical history of neurological problems since childhood, it is entirely possible that Marianne Chapman had the myelopathy condition that she attributes to Fixodent prior to her use of the denture cream, because her symptoms occurred before and after using Fixodent. See Guinn, 602 F.3d at 1254 ("Because [plaintiff] was diagnosed with diabetes only four years after beginning to take Seroquel, the temporal relationship in this case does not provide strong evidence of causation; in fact, it appears to equally indicate that [plaintiff] may have already developed diabetes before ever taking Seroquel." (emphasis added)). In addition, Dr. Greenberg recognized lymphoproliferative disorders as possible causes of Marianne Chapman's hematological syndrome and "malabsorption and gastric bypass surgery as potential causes for her copper-deficiency." In re Denture Cream Prods. Liab. Litig., 795 F.Supp.2d at 1366 (emphasis added).

A reliable differential analysis requires an expert to "compile a comprehensive list of hypotheses that might explain" a plaintiff's condition. Hendrix, 609 F.3d at 1195 (citation and internal quotation marks omitted). The "expert must provide reasons for rejecting alternative hypotheses using scientific methods and procedures and the elimination of those hypotheses must be founded on more than subjective beliefs or unsupported speculation." Id. at 1197 (citation and internal quotation marks omitted). An expert's failure to enumerate a comprehensive list of alternative causes and to eliminate those potential causes determines the admissibility of proposed specific-causation testimony. See Guinn, 602 F.3d at 1254 (determining no abuse of discretion in concluding the specific-causation expert's hypothesis was unreliable under Daubert, because of failure to consider possible alternative causes of plaintiff's diabetes).

Significantly, after concluding his report on Marianne Chapman, Dr. Greenberg performed an additional, reasonable test on her to determine if she had arterial venous malformation in her thoracic spinal cord. The judge found Dr. Greenberg's "failure to perform a test he considered reasonable before opining on the cause of Ms. Chapman's disease shows a lack of methodological rigor in reaching the diagnosis in his report," because he "did not consider the possibility of an idiopathic cause for Ms. Chapman's myelopathy." In re Denture Cream Prods. Liab. Litig., 795 F.Supp.2d at 1367. Dr. Greenberg failed to consider obvious alternative causes for Marianne Chapman's CDM, such as hereditary and acquired conditions known to cause myelopathies. See Guinn, 602 F.3d at 1257 (affirming exclusion of plaintiff's expert witness following Daubert proceedings, when the expert's testimony revealed facts casting "substantial doubt on whether Seroquel contributed to [plaintiff's] development of diabetes," since plaintiff "had multiple risk factors that could have been the sole cause of [her] diabetes[,] and [the expert] was unable to determine the relative risk of each factor"). Instead, Dr. Greenberg pursued his view that zinc-associated copper deficiency was responsible for Marianne Chapman's neurological and hematological symptoms. Yet, he provided no support for his hypothesis that Marianne Chapman's anemia, neutropenia, and myelopathy resulted from a single cause rather than several causes. He also omitted consideration of idiopathic causes for Marianne Chapman's CDM, additionally rendering his differential diagnosis unreliable. See Kilpatrick, 613 F.3d at 1342 ("The failure to take into account the potential for idiopathically occurring [disease] — particularly when [the disease] is a relatively new phenomenon in need of further study — placed the reliability of [the expert's] conclusions in further doubt.").

Obviously, there were numerous potential causes for Marianne Chapman's CDM that Dr. Greenberg did not analyze or consider. The district judge determined "Dr. Greenberg's differential diagnosis is not reliable as a matter of law in the Eleventh Circuit because he ruled-in and considered an etiology — Fixodent-induced copper-deficiency myelopathy — that has not been established to cause Ms. Chapman's disease." In re Denture Cream Prods. Liab. Litig., 795 F.Supp.2d at 1366. In reviewing the evidence presented and applying the applicable law, we conclude the district judge did not abuse her discretion or commit manifest error in precluding Dr. Greenberg's expert testimony regarding the specific causation of Marianne Chapman's CDM.

c. Exclusion of Other Expert Testimony

Because the judge determined neither the general nor specific-causation experts had proffered testimony that would prove the zinc in Fixodent had caused Marianne Chapman's CDM, she also excluded the testimonies of Dr. Wogalter and Dr. Von Frunhofer, whose testimonies were premised on the toxicity of Fixodent. In re Denture Cream Prods. Liab. Litig., 795 F.Supp.2d at 1367.

Id. The proposed testimony of Dr. Raffa concerned P & G's assets, which related to the punitive damages claim. Consequently, the judge precluded the proffered testimonies of these experts based on Rule 702 relevancy. We conclude there was no abuse of discretion or manifest injustice in granting P & G's motions preventing the testimonies of these three experts for the Chapmans.

B. Summary Judgment

After this court dismissed the parties' first appeal for lack of jurisdiction, based on our conclusion the Chapmans did not consider the district judge's Daubert order case-dispositive, the judge granted their Federal Rule of Civil Procedure 60(b) motion for relief from the final judgment. Thereafter, P & G moved for summary judgment and argued the Chapmans did not have an admissible expert witness to establish general or specific causation. In opposition, the Chapmans argued they had alternative expert witnesses to testify at trial, irrespective of the district judge's Daubert order. Concluding under the governing law the Chapmans had no experts to prove their products liability case alleging Fixodent was the cause of Marianne Chapman's CDM, the district judge granted summary judgment to P & G and entered final judgment.

The Chapmans' notice of appeal states they are appealing the summary judgment order and final summary judgment entered on July 31, 2012, "as well as all orders and rulings that produced that final judgment," including the order granting P & G's motions to exclude the testimony of the Chapmans' seven general and specific expert witnesses. Notice of Appeal (Aug. 27, 2012). We have considered fully the district judge's thorough Daubert order, which eliminated the Chapmans' expert witnesses, and concluded it was decided correctly under the controlling law. We now address the summary judgment order the Chapmans have appealed in conjunction with the Daubert order.17

We review a district judge's granting summary judgment de novo. Williams v. Mast Biosurgery USA, Inc., 644 F.3d 1312, 1318 (11th Cir.2011). Summary judgment is proper if the movant shows "there is no genuine dispute as to any material fact and the movant is entitled to judgment as a matter of law." Fed.R.Civ.P. 56(a). When a party fails to proffer a sufficient showing "to establish the existence of an element on which that party will bear the burden of proof at trial," there is no genuine dispute regarding a material fact. Williams, 644 F.3d at 1318 (citations, internal quotation marks, and ellipsis omitted). The burden for laying the proper foundation for admission of expert testimony is on the party offering the expert; admissibility must be shown by a preponderance of the evidence. Daubert, 509 U.S. at 592 n. 10, 113 S.Ct. at 2796 n. 10 (citing Bourjaily v. United States, 483 U.S. 171, 175-76, 107 S.Ct. 2775, 2778-79, 97 L.Ed.2d 144 (1987)). "Evidence inadmissible at trial cannot be used to avoid summary judgment." Corwin v. Walt Disney Co., 475 F.3d 1239, 1249 (11th Cir.2007) (citation, internal quotation marks, and alteration omitted).

The Chapmans opposed summary judgment for lack of expert witnesses following the Daubert order for three reasons: (1) their expert, Dr. Joseph Prohaska, a biochemistry professor at the University of Minnesota Medical School, could testify at trial, because P & G had not contested his proffered testimony; (2) they could call P & G experts and witnesses to testify that excessive ingestion of zinc can lead to copper deficiency, which can cause CDM; and (3) Marianne Chapman's treating physicians for her neuropathy could testify regarding causation. Because of the Chapmans' "periodic and contradictory insistence on having enough evidence to proceed to trial," the judge analyzed the merits of P & G's motion to make her decision "perfectly clear" for this court.18 Summ. J. Order at 6. In granting summary judgment to P & G, the district judge addressed the three possibilities for expert testimony the Chapmans had proffered following her Daubert order, precluding the testimonies of their general and specific causation experts, and concluded their alternative expert witnesses also were unavailing.

On appeal, the Chapmans challenge both the district judge's Daubert order and summary judgment granted to P & G, because the cumulative effect of these orders eliminated all potential causation experts the Chapmans had proffered. Their arguments for alternative expert witnesses are combined in the Chapmans' initial and reply briefs with their Daubert arguments, regarding their contention the district judge erred in disqualifying their original causation experts. See, e.g., Appellants' Br. at 18 n. 5, 22-23, 25, 30-31, 40, 43, 44-46, 47, 48-49, 50, 56, 60; Appellants' Reply Br. at 4 n. 1, 6, 8, 11, 14, 16-17, 18, 21, 22, 24, 30. The alternative expert witnesses the Chapmans propounded following the Daubert order and precluded by summary judgment granted to P & G necessarily had to satisfy the same Daubert review standards to testify concerning causation for the Chapmans to prove their case that Fixodent caused Marianne Chapman's CDM.

The Chapmans discuss Dr. Prohaska19 and P & G experts and witnesses20 in their initial and reply briefs in connection with their contention that the medical community generally accepts excess zinc can cause CDM. Appellants' Br. at 27-33; Appellants' Reply Br. at 3-6. Accepting this classification would place this case in McClain category one, which would eliminate the Daubert analysis of the Chapmans' experts, if it were generally accepted by the medical community that zinc causes CDM. We give the Chapmans "the benefit of the doubt" that these first two sources of alternative expert witnesses have been presented on appeal in their briefs. Carmichael v. Kellogg, Brown & Root Servs., Inc., 572 F.3d 1271, 1293 (11th Cir.2009). The district judge noted "Dr. Prohaska's report was limited to hematological disorders, not myelopathy, and is therefore irrelevant." Summ. J. Order at 7. Although the Chapmans "may show zinc blocks copper absorption, this alone cannot constitute a showing of general or specific causation." Id. at 8; see Rider, 295 F.3d at 1202 (noting causation evidence of one type of stroke "does not apply to situations involving" another type of stroke). Moreover, she decided "there was no mechanistic evidence regarding the absorption of zinc from Fixodent itself." Summ. J. Order at 8. In performing the requisite gatekeeping function, a trial judge's assessment of proposed testimony does not mean "`taking the expert's word for it.'" Frazier, 387 F.3d at 1261 (quoting Fed.R.Evid. 702 Advisory Committee Notes (2000 Amends.)). We also conclude that Dr. Prohaska's testimony cannot provide admissible proof the Chapmans need to establish their case at trial, because his expertise is hematology and not myelopathy at issue in this case.

In addition, the judge explained the Chapmans "cannot create a triable issue of fact as to causation" with P & G experts and witnesses, who have not submitted the requisite epidemiological or clinical reports. Summ. J. Order at 9. Expert witnesses, who are expected to testify at trial, must be identified in the Joint Pretrial Stipulation and must meet the procedural requirements of Federal Rule of Civil Procedure 26(a)(2), including time designations for supplying disclosures and reports, regarding expert testimony to be given. The Chapmans proposed their ability to use P & G experts and witnesses at trial almost six months after the judge's scheduled January 24, 2011, deadline for identifying experts, making complying with the procedural timely notice and disclosure requirements of Rule 26(a)(2), including reports of testimony, impossible.21 See Fed.R.Civ.P. 26(a)(2)(D) (stating a party "must" disclose expert testimony "at the times and in the sequence that the court orders"). "District courts have broad discretion to exclude untimely disclosed expert-witness testimony." Pride v. BIC Corp., 218 F.3d 566, 578 (6th Cir.2000).

Even if the Chapmans had satisfied the procedural requirements of Rule 26(a)(2) to use P & G experts and witnesses to testify for them at trial, the district judge concluded the Chapmans could not prove their case with them. P & G's experts had "reached the conclusion that Fixodent does not cause CDM."22 Summ. J. Order at 9. The judge determined the Chapmans had "not made a sufficient showing that [P & G's] expert testimony would withstand the Daubert analysis of [her] June 13 Order and yield the conclusion they seek, in view of [P & G's] experts' testimony as a whole." Id. Deciding the P & G witnesses ultimately did not support the Chapmans' conclusion that Fixodent caused Marianne Chapman's CDM, the judge explained the Chapmans "cannot perform an end run around the [Daubert] Order by calling witnesses who have not been vetted for reliability." Id. The judge also noted P & G's expert, Dr. Laura W. Katzan, cannot "establish general causation, a necessary element of their claims," by differential diagnosis. Id. (citing McClain, 401 F.3d at 1253). Considering the prospective testimonies of P & G experts and witnesses in context, the judge properly decided the Chapmans could not prove their case with admissible evidence from these alternative experts and witnesses.

At a status conference the day after issuance of the Daubert order, the Chapmans' counsel argued for the first time they still could try to prove causation through "treating experts who have opined [Marianne Chapman's] condition was caused by her use of Fixodent that were not the subject of the Daubert motion." Hr'g Tr., June 14, 2011, at 7:21-8:1 (emphasis added). In recasting Marianne Chapman's treating physicians as "treating experts," the Chapmans sought to have these doctors testify concerning their personal treatment of Marianne Chapman as well as their view of the cause of her CDM. The judge, however, explained in her summary judgment order that treating physicians, who diagnosed Marianne Chapman's CDM, are fact and not expert witnesses.23 Summ. J. Order at 10 (citing Hendrix, 609 F.3d 1183). The Chapmans have not briefed on appeal their district-court argument in opposing summary judgment that Marianne Chapman's treating physicians could testify as experts at trial. "The `law is by now well settled in this Circuit that a legal claim or argument that has not been briefed before the court is deemed abandoned and its merits will not be addressed.'" Carmichael, 572 F.3d at 1293 (quoting Access Now, Inc. v. Sw. Airlines Co., 385 F.3d 1324, 1330 (11th Cir.2004)). Consequently, we conclude the Chapmans have abandoned on appeal their argument that Marianne Chapman's treating physicians could have testified as experts at trial. Because none of the Chapmans' alternative sources for expert witnesses could provide evidence admissible at trial "to avoid summary judgment," the district judge appropriately granted summary judgment to P & G. Corwin, 475 F.3d at 1249 (citations and internal quotation marks omitted).

III. CONCLUSION

To prove Fixodent caused Marianne Chapman's CDM, the Chapmans were required to have Daubert-qualified, general and specific-causation-expert testimony that would be admissible at trial to avoid summary judgment. Guinn, 602 F.3d at 1252. With the district judge's properly analyzed Daubert order, the Chapmans lost their designated general and specific-expert witnesses, because of deficiencies in the experts' scientific-methodology reliability. Their attempts to proffer alternative causation-expert witnesses failed, because their prospective testimony was inadmissible substantively, procedurally, or abandoned on appeal. Summary judgment correctly was granted to P & G.

AFFIRMED.

JORDAN, Circuit Judge, concurring:

Given the "due deference" that the abuse of discretion standard embodies, see Gall v. United States, 552 U.S. 38, 59, 128 S.Ct. 586, 169 L.Ed.2d 445 (2007), and the "range of choice" permitted by that standard, see In re Rasbury, 24 F.3d 159, 168 (11th Cir.1994), I agree that we should affirm the district court's exclusion of the Chapmans' general causation experts. I would, therefore, not address any of the other issues raised by the Chapmans.

Specifically, I would not suggest, as the court does in dictum, that the district court could have properly prevented the Chapmans from relying on Procter & Gamble's own experts. The district court addressed the Chapmans' reliance on some of the defense experts on the merits and did not exclude those experts under Rule 26 of the Federal Rules of Civil Procedure. So there is no need to hypothesize about how we would rule if the district court had decreed that such reliance by the Chapmans was procedurally improper. Moreover, P & G does not assert Rule 26 on appeal, and some cases hold that, because there is no surprise or prejudice, a party is permitted to use and rely on the expert testimony presented by the opposing party. See, e.g., Nat'l Railroad Passenger Corp. v. Certain Temporary Easements, 357 F.3d 36, 42 (1st Cir.2004) (no abuse of discretion in allowing plaintiff to call defense expert in its case-in-chief); Kerns v. Pro-Foam of South Alabama, 572 F.Supp.2d 1303, 1309-12 (S.D.Ala.2007) (failure of plaintiff to disclose defendant's expert as its own expert did not prevent plaintiff from calling that expert during its case-in-chief). If we are going to opine on this issue, we should wait for a case which directly presents it.

In closing, I recognize that the district court at times used language which might be seen as opining on the ultimate persuasiveness of the theories advanced by the Chapmans' experts. But given its numerous accurate statements of the correct standard under Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993), I do not think the district court applied an incorrect (or improperly onerous) legal standard.