Full opinion text
OPINION AND ORDER AIKEN, Chief Judge: In these related products liability actions, plaintiffs allege that they developed glenohumeral chondrolysis, the rapid and permanent loss of cartilage in the shoulder joint, after medical devices known as “pain pumps” were used to administer local anesthetics during and after arthroscopic surgery. Plaintiffs each seek non-economic damages of $4,500,000 and economic damages ranging from $1,050,000 to $1,500,000 (or damages to be proven at trial), and against certain defendants, punitive damages. Several plaintiffs also seek damages for loss of consortium. Before the court are defendants’ motions to exclude the general causation testimony of nine expert witnesses: Stephen Badylak, M.D.; Carl Basamania, M.D.; Charles Beck, M.D.; Jason Dragoo, M.D.; Sander Greenland, PhD; Frederick Matsen, M.D.; John Swanson, M.D.; Stephen Trippel, M.D.; and Martin Wells, PhD. Defendants contend that the testimony of these experts is unreliable, irrelevant, and inadmissible under Federal Rule of Evidence 702 and Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993). Defendants also move to strike the testimony of Drs. Basamania and Matsen for failing to disclose information relevant to their expert opinions in violation of Federal Rule of Civil Procedure 26(a)(2)(B). Plaintiffs oppose the motions and, in turn, move to exclude the testimony of two defense expert witnesses, William Stetson, M.D. and Wayne Burk-head, Jr., M.D. On November 17 and 18, 2009 and March 17, 2010 the court heard oral argument and brief testimony on the parties’ motions after submission of extensive briefing. For the reasons set forth below, defendants’ motions are granted with respect to the testimony of Frederick Mat-sen, M.D., Sander Greenland, PhD, and Martin Wells, PhD, granted in part with respect to Carl Basamania, M.D., and denied in all other respects. Plaintiffs’ motions are denied. BACKGROUND The glenohumeral joint is the ball-and-socket joint of the shoulder. A fibrous capsule encases the joint space, an area surrounding the joint that contains articular cartilage and synovial tissue. Articular cartilage is the thin layer of tissue that covers the ends of bones in the joint and provides a smooth, gliding surface to enable the bones to move. Unlike other types of tissue, articular cartilage has no nerves or blood supply and receives nutrients from synovial fluid within the joint space. Synovial tissue produces the synovial fluid which carries and diffuses nutrients into articular cartilage cells (chondrocytes) to continually renew the matrix of cartilage. In other words, synovial fluid is the “lifeblood” of articular cartilage. Trippel Expert Report, p. 4. Glenohumeral chondrolysis is a very rare condition that results from the rapid and permanent destruction of articular cartilage in the shoulder joint. “Simply described, chondrolysis is the degeneration of cartilage cells, ending in cell death.” D.J. Solomon et al., Glenohumeral Chondrolysis After Arthroscopy: A Systematic Review of Potential Contributors and Causal Pathways, 25 Arthroscopy: J. Arthroscopic & Related Surg. 1329, 1330 (Nov.2009). Cartilage cell death may occur from the inability of chondrocytes to maintain or produce cartilage matrix. Id. If not renewed, the cartilage matrix wears away with normal use of the joint until no protective tissue remains. The bones of the joint then rub against one another, causing debilitating pain and stiffness. Treatment options for chondrolysis are few, as shoulder joint replacement surgery has met with limited success. See J. Levy et al., Young Patients with Shoulder Chondrolysis Following Arthroscopic Shoulder Surgery Treated with Total Shoulder Arthroplasty, 17 J. Shoulder Elbow Surg. 380, 387 (May 2008) (“After nonoperative measures are exhausted, there are few options available for the patient who presents with chondrolysis after shoulder arthroscopy.”). Very few cases of chondrolysis were reported until the late 1990s when researchers described several patients who developed glenohumeral chondrolysis after receiving injections of gentian violet, a color contrast dye, during open surgery. See K. Tamai et al., Chondrolysis of the Shoulder Following a “Color Test”-Assisted Rotator Cuff Repair, 68 Acta Orthop. Scand. 401(Aug.l997); Y. Nakagawa et al., Glenohumeral Osteoarthritis Following a “Color Test” During Rotator Cuff Repair, 57 Bull Hosp. Jt. Dis. 216 (1998). Case reports during this time also identified a surgical irrigation solution and an acrylic bone cement as likely causes of cartilage destruction in the knee and hip joints. C. Douw et al., Clinical and Pathological Changes in the Knee After Accidental Chlorhexidine Irrigation During Arthroscopy: Case Reports and Review of the Literature, 80 J. Bone & Joint Surg. 437 (May 1998); A. van Huyssteen & D. Bracey, Chlorhexidine and Chondrolysis in the Knee, 81 J. Bone & Joint Surg. (U.K.) 995 (Nov.1999); W. Leclair et al., Rapid Chondrolysis After an Intra-Articular Leak of Bone Cement in Treatment of a Benign Acetabular Subchondral Cyst: An Unusual Complication of Percutaneous Injection of Acrylic Cement, 29 Skeletal Radiol 275 (May 2000). Still other cases of articular cartilage damage were reported after the use of radiofrequency devices (known as thermal devices or wands) and suture anchors during arthroscopic surgery. See R. Edwards et al., Thermal Chondroplasty of Chondromalacia Human Cartilage, 30 Am. J. Sports Med. 90 (Jan.2002); W. Levine et al., Chondrolysis Following Arthroscopic Thermal Capsulorrhaphy to Treat Shoulder Instability, 87 J. Bone & Joint Surg. 616 (Mar.2005); see also G. Athwal et al., Osteolysis and Arthropathy of the Shoulder After Use of Bioabsorbable Knotless Suture Anchors, 88 J. Bone & Joint Surg. 1840 (Aug.2006); C. Good et al., Glenohumeral Chondrolysis After Shoulder Arthroscopy with Thermal Capsulorrhaphy, 23 Arthroscopy 797 (July 2007); B. Coobs & R. LaPrade, Severe Chondrolysis of the Glenohumeral Joint After Shoulder Thermal Capsulorrhaphy, 38 Am J. Orthop. E34 (2009). In 2004, surgeons reported three cases of glenohumeral chondrolysis in young athletes following arthroscopic shoulder surgeries. Thermal devices were used during two of the surgeries, and one patient reportedly received a pain pump infused with bupivacaine and epinephrine, though the report is unclear whether the pain pump was placed intra-articularly. D. Petty et al., Glenohumoral Chondrolysis After Shoulder Arthroscopy: Case Reports and Review of Literature, 32 Am. J. Sports Med. 509, 511 (Mar.2004). The authors suspected that thermal devices played a role in two of the three cases of chondrolysis but made no findings with respect to pain pump use. Id. at 514. Beginning in 2003, Dr. Charles Beck, an orthopedic surgeon in Utah, observed that several of his patients developed chondrolysis after he performed arthroscopic surgeries and inserted pain pumps to administer bupivacaine and epinephrine directly into the shoulder joint. Dr. Beck eventually reviewed the medical records of patients involved in 152 shoulder arthroscopies and determined that chondrolysis developed in 12 of 19 (or 63%) of shoulders that received intra-articular continuous infusion of anesthetics via pain pump, while no cases of chondrolysis were reported in shoulders that were not treated with a pain pump. In July 2005, Dr. Beck presented his findings to a group of orthopedic surgeons. He and a colleague, Dr. Brent Hansen, wrote a paper analyzing his research, and in July 2007 their paper was published in the American Journal of Sports Medicine. See B. Hansen & C. Beck, Postarthroscopic Glenohumeral Chondrolysis, 35 Am. J. Sports Med. 1628 (July 2007) [hereinafter Hansen/Beck Study]. Physicians and researchers have published additional reports of glenohumeral chondrolysis after arthroscopic surgery and discussed potential causes of the disease, including the use of pain pumps for continuous infusion of local anesthetics. See, e.g., P. Greis et al., Bilateral Shoulder Chondrolysis Following Arthroscopy, 90 J. Bone & Joint Surg. 1338 (June 2008); S. Anderson et al., Chondrolysis of the Glenohumeral Joint — - Abstract, 24 J. Arthroscopy Supp. el3 (Apr. 2008); A. McNickle et al., Postsurgical Glenohumeral Arthritis in Young Adults, — Am. J. Sports Med.-- (June 2009); M. Saltzman et al., Postsurgical Chondrolysis of the Shoulder, 32 Orthopedics 215 (June 2009); D. Bailie & T. Ellenbeeker, Severe Chondrolysis After Shoulder Arthroscopy: A Case Series, — J. Shoulder Elbow Surg.-(Jan.2009). Further, researchers have conducted in vitro and animal studies on the chondrotoxicity of local anesthetics. N. Dogan et al., The Effects of Bupivacaine and Neostigmine on Articular Cartilage and Synovium in the Rabbit Knee Joint, 32 J. Int’l Med. Res. 513 (Sept.2004); C. Chu et al., In Vitro Exposure to 0.5% Bupivacaine is Cytotoxic to Bovine Articular Chondrocytes, 22 Arthroscopy 693 (July 2006) [Chu I]; A. Gomoll et al., Chondrolysis After Continuous Intra-Articular Bupivacaine Infusion, 22 Arthroscopy 813 (Aug.2006) [Gomoll I]; J. Karpie & C. Chu, Lidocaine Exhibits Dose- and Time-Dependent Cytotoxic Effects on Bovine Articular Chondrocytes In Vitro, 35 Am. J. Sports. Med. 1621 (Oct.2007); S. Piper & H. Kim, Comparison of Ropivacaine and Bupivacaine Toxicity in Human Articular Chondrocytes, 90 J. Bone & Joint Surg. 986 (May 2008); Chu et al., The In Vitro Effects of Bupivacaine on Articular Chondrocytes, 90 J. Bone & Joint Surg. 814 (U.K.) (June 2008) [Chu II]; J. Dragoo et al., The Effect of Local Anesthetics Administered Via Pain Pump on Chondrocyte Viability, 36 Am. J. Sports Med. 1484 (Aug.2008); Go-moll et al., Long-Term Effects of Bupivacaine on Cartilage in a Rabbit Shoulder Model, 37 Am. J. Sports Med. 72, 75-76 (Jan.2009) [Gomoll II]; Lo et al., Local Anesthetics Induce Chondrocyte Death in Bovine Articular Cartilage Disks in a Dose- and Duration-Dependent Manner, 25 Arthroscopy: J. Arthroscopic & Related Surg. 707 (July 2009). Finally, authors have published reviews of the relevant medical literature. B. Bus-field & D. Romero, Pain Pump Use After Shoulder Arthroscopy as a Cause of Glenohumeral Chondrolysis, 25 Arthroscopy 647 (Jan.2009); E. Fester & F. Noyes, Postoperative Chondrolysis of the Knee: 3 Case Reports and Revieiv of the Literature, — Am. J. Sports Med. 1 (July 2009); R. Kang et al., Complications Associated with Anterior Shoulder Instability Repair, 25 Arthroscopy 909 (Aug.2009). In November 2009, the Food and Drug Administration (FDA) issued a bulletin entitled “Information for Healthcare Professionals — Chondrolysis Reported with Continuously Infused Local Anesthetics.” Horwitz Decl. in Supp. Defs.’ Suppl. Mem., Ex. H (updated Feb. 16, 2010). The bulletin states that upon reviewing 35 reports of chondrolysis, “[t]he significance of this injury to otherwise healthy young adults warrants notification to health care professionals ... to follow the instructions for use of elastomeric infusion devices, and to not use these devices for continuous intraarticular infusion of local anesthetics after orthopedic surgery.” Id. Ex. H, p. 1. The FDA made clear that “[n]either local anesthetics nor infusion devices are approved for an indication of continuous intra-articular infusion.” Id. The FDA further announced that it “is requiring the drug manufacturers to update their product labels to warn healthcare professionals about this potential serious adverse effect” and “is also exploring possible options for addressing the safety issues with the infusion devices (e.g., labeling changes, etc.).” Id. On August 31, 2007, the first pain pump products liability action was filed in this district, and 23 cases are now pending before the court. Plaintiffs allege that the intra-articular use of pain pumps to administer a continuous infusion of local anesthetics [hereinafter referred to as “continuous infusion”] either caused or substantially contributed to their development of glenohumeral chondrolysis. Plaintiffs bring suit against the manufacturers and distributors of the accused pain pumps, including Stryker Corp., Stryker Sales Co., McKinley Medical L.L.C., DJO, L.L.C., I-Flow Corp., and Pacific Medical, Inc. Plaintiffs allege claims of defective design and labeling, failure to warn, and negligence based on defendants’ failure to warn physicians of the risks associated with the intra-articular use of pain pumps and defendants’ manufacture and promotion of pain pumps for intra-articular uses that were not approved by the FDA. The parties agree that plaintiffs must present evidence of both general and specific causation to prevail on their claims. “General causation is established by demonstrating, often through a review of scientific and medical literature, that exposure to a substance can cause a particular diseasef,]” while specific causation “is established by demonstrating that a given exposure is the cause of an individual’s disease[.]” Reference Manual On Scientific Evidence, 444 (Fed. Judicial Ctr.2d ed. 2000) [Reference Manual] (emphasis added); see also Golden v. CH2M Hill Hanford Group, Inc., 528 F.3d 681, 683 (9th Cir.2008). Thus, plaintiffs must present expert testimony to show by a preponderance of the evidence that continuous infusion can and did cause plaintiffs’ chondrolysis. See Joshi v. Providence Health Sys. of Oregon Corp., 198 Or.App. 535, 536-37, 108 P.3d 1195 (2005) (when causation involves a complex medical question, Oregon law requires expert testimony establishing “a reasonable medical probability” of causation). Per the parties’ agreement, the instant motions are limited to whether plaintiffs’ experts offer reliable testimony on general causation. APPLICABLE LAW Federal Rule of Evidence 702 (Rule 702) governs the admissibility of expert testimony. Rule 702 permits a qualified expert to present testimony that “will assist the trier of fact” in understanding the evidence or in determining a factual issue, so long as “(1) the testimony is based upon sufficient facts or data, (2) the testimony is the product of reliable principles and methods, and (3) the witness has applied the principles and methods reliably to the facts of the case.” Fed.R.Evid. 702; see also Daubert, 509 U.S. at 593-95, 113 S.Ct. 2786. “In short, an expert’s conclusion must meet the ‘trilogy of restrictions on expert testimony: qualification, reliability and fit.’ ” In re Human Tissue Prods. Liab. Litig., 582 F.Supp.2d 644, 655 (D.N.J.2008) (quoting Schneider v. Fried, 320 F.3d 396, 404 (3d Cir.2003)). The proponent of the evidence must prove its admissibility by a preponderance of the evidence. Daubert, 509 U.S. at 592 n. 10, 113 S.Ct. 2786. Rule 702 codifies the reliability requirements set forth in Daubert and subsequent Supreme Court decisions. See Kumho Tire Co. v. Carmichael, 526 U.S. 137, 119 S.Ct. 1167, 143 L.Ed.2d 238 (1999); Gen. Elec. Co. v. Joiner, 522 U.S. 136, 118 S.Ct. 512, 139 L.Ed.2d 508 (1997). Prior to Daubert, the admissibility of expert testimony was governed by “the traditional ‘general acceptance’ test enunciated in Frye v. United States, which required that a scientific technique be generally accepted in the relevant scientific community to be admissible.” In re Fosamax Prods. Liab. Litig., 645 F.Supp.2d 164, 172 (S.D.N.Y.2009). In finding the Frye test superceded by the Federal Rules of Evidence, the Supreme Court in Daubert explained that “a rigid general acceptance requirement would be at odds with the liberal thrust of the Federal Rules and their general approach of relaxing the traditional barriers to opinion testimony.” Daubert, 509 U.S. at 588, 113 S.Ct. 2786 (quotation marks and citations omitted). At the same time, the Supreme Court recognized the limits of “purportedly scientific evidence.” Id. at 589,113 S.Ct. 2786. Under Daubert, the trial judge bears the responsibility of “gatekeeper” to ensure “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. 2786. This inquiry requires “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.” Id. at 592-93, 113 S.Ct. 2786. “Pertinent evidence based on scientifically valid principles will satisfy those demands.” Id. at 597,113 S.Ct. 2786. Reliable testimony must be grounded “in the methods and procedures of science,” and signify knowledge beyond “subjective belief or unsupported speculation.” Daubert, 509 U.S. at 590, 113 S.Ct. 2786. Generally, the court’s analysis focuses on the methodology underlying an expert’s testimony rather than the expert’s ultimate conclusions. Daubert, 509 U.S. at 595, 113 S.Ct. 2786. At the same time, “conclusions and methodology are not entirely distinct from one another,” and “[a] court may conclude that there is simply too great an analytical gap between the data and the opinion proffered.” Joiner, 522 U.S. at 146,118 S.Ct. 512. Daubert identifies four factors that the court may consider in assessing reliability, including: 1) whether a theory or technique can be and has been tested; 2) whether a theory has been subjected to peer review and publication; 3) whether a “particular scientific technique” has a known or potential rate of error; 4) and whether the theory or technique enjoys general acceptance within the “relevant scientific community.” Daubert, 509 U.S. at 593-94, 113 S.Ct. 2786. However, “Daubert makes clear that the factors it mentions do not constitute a ‘definitive checklist or test.’ ” Kumho, 526 U.S. at 150, 119 S.Ct. 1167 (quoting Daubert, 509 U.S. at 593,113 S.Ct. 2786). Rather, these factors “may or may not be pertinent in assessing reliability, depending on the nature of the issue, and expert’s particular expertise,” and the subject matter of the proffered testimony. Id. (citation omitted). Relevant expert testimony “logically advances a material aspect of the proposing party’s case.” Daubert v. Merrell Dow Pharm., Inc., 43 F.3d 1311, 1315 (9th Cir.1995) (Daubert II). An expert’s testimony must assist the trier of fact and relate to, or “fit,” the underlying facts of the case. Id. at 591, 113 S.Ct. 2786. Though the court must ensure that an expert’s opinion is supported by sufficient data and reliable methodology, the inquiry is “a flexible one,” depending on “the particular circumstances of the particular case at issue.” Kumho, 526 U.S. at 150, 119 S.Ct. 1167. In other words, an expert’s testimony must rest on “good grounds, based on what is known.” Daubert, 509 U.S. at 590, 113 S.Ct. 2786. Ultimately, the court must ensure that an expert “employs in the courtroom the same level of intellectual rigor that characterizes the practice of an expert in the relevant field,” Kumho, 526 U.S. at 152, 119 S.Ct. 1167, such that the expert’s “work product amounts to ‘good science.’ ” Daubert II, 43 F.3d at 1315 (quoting Daubert, 509 U.S. at 593, 113 S.Ct. 2786). DISCUSSION At first glance, the reliability of plaintiffs’ experts’ testimony seems fairly straightforward. Plaintiffs’ experts opine that, to a reasonable degree of medical probability, continuous infusion can cause chondrolysis. Eminently qualified, plaintiffs’ experts base their opinions on their knowledge and experience, in vitro (laboratory) and animal studies demonstrating the chondrotoxicity of local anesthetics typically used with continuous infusion, case reports associating continuous infusion with chondrolysis, and the temporal relationship between the use of continuous infusion and the increased and unprecedented reports of chondrolysis. Yet, defendants assert numerous challenges against the admission of plaintiffs’ expert testimony. Defendants argue that medical science lacks sufficient facts or data regarding the cause of chondrolysis, and no conclusive evidence, such as epidemiological studies, establishes a causal link. Absent such evidence, defendants maintain that plaintiffs’ opinions are unreliable products of litigation research that lack peer review, general acceptance in the profession, or any hallmark of scientific validity. Given their broad application, I address these arguments before discussing the opinions of individual experts. A. Certainty of Evidence Supporting General Causation Defendants argue that plaintiffs’ experts erroneously and unreliably “rule in” continuous infusion as a cause of chondrolysis, despite the prevalence of uncertain and inconclusive data. In support of their argument, defendants cite several chondrolysis studies, including Dr. Beck’s, which submit that the exact cause of chondrolysis and its biological mechanism is “unclear,” “unknown,” “speculative,” “multifactorial,” and requires “further study.” Hansen, p. 1628; Bailie, p. 2; Greis, p. 1338; Busfield, p. 651; Levy, p. 384; Go-moll I, p. 814, Solomon, pp. 1339-41; see also Basamania Dep., Aug. 15, 2009, p. 410-11 (“[T]he best we can say at this point in time is that it appears multifactorial. It could be a dilution, it could be pH, it could be inhibition of the synovial cells to produce more fluids.”). While defendants concede that some of the medical literature supports an association between continuous infusion and chondrolysis, they maintain that association is distinct from and cannot reliably support causation. See Siharath v. Sandoz Pharm. Corp., 131 F.Supp.2d 1347, 1372 (N.D.Ga.2001) (“Doctors in their day-today practices stumble upon coincidental occurrences and random events and often follow human nature, which is to confuse association and causation.”). Absent conclusive evidence of causation, defendants insist that plaintiffs’ experts’ opinions are unreliable “ ‘leaps of faith’ unsupported by good science.” Kilpatrick v. Breg, Inc., 2009 WL 2058384, at *3 (S.D.Fla. June 25, 2009) (quoting Rider v. Sandoz Pharm., 295 F.3d 1194, 1202 (11th Cir.2002)). Defendants’ mantra of conclusive causal evidence repeats throughout their various arguments. Whether challenging the scientific validity of expert methodologies, the general acceptance of expert opinion, or the influence of litigation, defendants repeatedly and consistently revert to what is the essence of their Daubert motions: plaintiffs’ experts cannot testify that continuous infusion causes glenohumeral ehondrolysis because no medical or epidemiological study conclusively says it does. Taking defendants’ argument to its logical conclusion, defendants would have plaintiffs prove causation to a medical certainty before expert testimony could be admitted. I find defendants’ argument wholly inconsistent with Daubert and the fundamental premise of Rule 702. Rule 702 permits expert testimony that is helpful to the trier of fact, reliable, and relevant. To that end, Daubert was intended to exclude “junk science” — unsupported testimony or evidence cloaked in the credentials of a testifying expert — that would confuse or mislead rather than “assist the trier of fact.” Best v. Lowe’s Home Ctrs., Inc., 563 F.3d 171, 176-77 (6th Cir.2009) (“Daubert attempts to strike a balance between a liberal admissibility standard for relevant evidence on the one hand and the need to exclude misleading ‘junk science’ on the other.”). Daubert did not, however, impose an “exacting standard of causality” beyond the preponderance of the evidence “simply because scientific issues are involved.” In re Ephedra Prods. Liab. Litig., 393 F.Supp.2d 181, 190 (S.D.N.Y.2005). “It would be unreasonable to conclude that the subject of scientific testimony must be ‘known’ to a certainty; arguably, there are no certainties in science.” Daubert, 509 U.S. at 590, 113 S.Ct. 2786; see also Basamania Dep. Aug. 15, 2009, p. 435 (“There’s [sic] very few things in medie[ine] where it’s absolutely established that X [causes] Y.”). Moreover, “[l]ack of certainty is not, for a qualified expert, the same thing as guesswork.” Primiano v. Cook, — F.3d -, -, 2010 WL 1660303, at *5 (9th Cir. Apr.27, 2010). Consequently, the proper focus under Daubert is whether an expert’s testimony rests on evidence reliably derived from scientific methodology and is relevant to the facts of the case, not whether plaintiffs’ experts can prove the point of their testimony. Ambrosini v. Labarraque, 101 F.3d 129, 135 (D.C.Cir.1996) (“The dispositive question is whether the testimony will ‘assist the trier of fact to understand the evidence or to determine a fact in issue,’ not whether the testimony satisfies the plaintiffs burden on the ultimate issue at trial.”) (citation omitted). Indeed, establishing reliability should not mean that plaintiffs “have to prove their case twice— they do not have to demonstrate to the judge by a preponderance of the evidence that the assessments of their experts are correct, they only have to demonstrate by a preponderance of evidence that their opinions are reliable.” In re Paoli R.R. Yard PCB Litig., 35 F.3d 717, 744 (3d Cir.1994); Allison v. McGhan Med. Corp., 184 F.3d 1300, 1312 (11th Cir.1999) (accord); In re Ephedra, 393 F.Supp.2d at 193 (“Daubert’s dictum about scientific validity” is not “authority for increasing the burden of proof imposed by substantive law”). Reliability under Daubert does not depend on “the correctness of the expert’s conclusions but [on] the soundness” of the methodology. Daubert II, 43 F.3d at 1318. Thus, even if the medical evidence asserts “only” an association between continuous infusion and chondrolysis, plaintiffs’ experts’ testimony should not be excluded if they adequately explain why the association is valid and how causation can be inferred from it. Kennedy v. Collagen Corp., 161 F.3d 1226, 1229-30 (9th Cir.1998); see also United States v. W.R. Grace, 504 F.3d 745, 766 (9th Cir.2007); Heller v. Shaw Indus., Inc., 167 F.3d 146, 154-55 (3d Cir.1999); In re Ephedra, 393 F.Supp.2d at 190 (Rule 702 is one of threshold admissibility and does not preclude evidence of a kind typically relied on by experts in the relevant field). “A trial court should admit medical expert testimony if physicians would accept it as useful and reliable, but it need not be conclusive because medical knowledge is often uncertain.” Primiano, — F.3d at-, 2010 WL 1660303, at *5 (quotation marks and citation omitted). This is particularly true where plaintiffs’ experts need only testify to a medically reasonable probability of causation between continuous infusion and chondrolysis. Baughman v. Pina, 200 Or. App. 15, 18, 113 P.3d 459 (2005). Defendants nonetheless argue that plaintiffs’ experts cannot “rule in” continuous infusion as a cause of chondrolysis through the differential diagnosis methodology without conclusive evidence of causation. Defendants maintain that a differential diagnosis typically “rules out” suspected causes to establish specific causation, but only after the accused product or agent has been “ruled in” as a causative factor. See Ruggiero v. Warner-Lambert Co., 424 F.3d 249, 254 (2d Cir. 2005); see, e.g., Norris v. Baxter Healthcare Corp., 397 F.3d 878, 885 (10th Cir.2005); In re Rezulin Prods. Liab. Litig., 2004 WL 2884327, at *4 (S.D.N.Y. Dec. 10, 2004); Hall v. Baxter Healthcare Corp., 947 F.Supp. 1387, 1413 (D.Or.1996). Thus, because continuous infusion has not been proven as a cause of chondrolysis, defendants argue that differential diagnosis is not reliable to establish general causation. I disagree. “Differential diagnosis, or differential etiology, is a standard scientific technique of identifying the cause of a medical problem by eliminating the likely causes until the most probable one is isolated.” Westberry v. Gislaved Gummi AB, 178 F.3d 257, 262 (4th Cir.1999); Reference Manual, p. 443. Here, several of plaintiffs’ experts applied differential diagnosis in developing their opinions that continuous infusion can cause chondrolysis. See Badylak Expert Report, p. 3; Beck Expert Report, pp. 13-15; Swanson Expert Report, p. 4; Trippel Expert Report, p. 14; Beck Grossnickle testimony, Mar. 3, 2009, Yol. 5A, p. 1107 (“I believe there’s an association with this same condition because I can’t find any other reason for it.”); Basamania Dep. Aug. 15, 2009, p. 428 (“[C]hondrolysis was an exceedingly rare occurrence until the introduction of these [pain pumps].”). Several courts agree that the differential diagnosis methodology “does not (necessarily) support an opinion on general causation, because, like any process of elimination, it assumes that the final, suspected ‘cause’ remaining after this process of elimination must actually be capable of causing the injury.” See Ruggiero, 424 F.3d at 254 (quotation marks and citation omitted); Henricksen v. ConocoPhillips Co., 605 F.Supp.2d 1142, 1158 (E.D.Wash. 2009) (“[D]ifferential diagnosis cannot demonstrate general causation, because it assumes, without proving, that all of the potential causes considered are capable of causing the condition at issue.”); Hall, 947 F.Supp. at 1413 (“Indeed, differential diagnosis assumes that general causation has been proven for the list of possible causes it eliminates!.]”). At the same time, “[t]here may be instances where, because of the rigor of differential diagnosis performed, the expert’s training and experience, the type of illness or injury at issue, or some other case-specific circumstance, a differential diagnosis is sufficient to support an expert’s opinion in support of both general and specific causation.” Ruggiero, 424 F.3d at 254. I find this to be one of those instances. Unlike the majority of cases in which differential diagnosis was held insufficient to rule in a potential causative factor, plaintiffs here do not allege toxic exposure through air, water, or groundwater contamination, or through the ingestion of a pharmaceutical drug. See, e.g., Ruggiero, 424 F.3d at 251; Henricksen, 605 F.Supp.2d at 1148-49; Bickel v. Pfizer, 431 F.Supp.2d 918, 923-24 (N.D.Ind.2006); In re Rezulin Prods. Liab. Litig., 369 F.Supp.2d 398, 436-37 (S.D.N.Y.2005); Siharath, 131 F.Supp.2d at 1349-50; Cavallo v. Star Enter., 892 F.Supp. 756, 771 (E.D.Va.1995). Nor do plaintiffs allege that exposure to toxins, medications, or medical products caused cancer, stroke, birth defects, or other systemic disease or injury unrelated to the area or purpose of exposure. See, e.g., Hollander v. Sandoz Pharm. Corp., 289 F.3d 1193, 1210-11 (10th Cir.2002); Raynor v. Merrell Pharm. Inc., 104 F.3d 1371, 1375-76 (D.C.Cir.1997); Doe v. Ortho-Clinical Diagnostics, Inc., 440 F.Supp.2d 465, 476-77 (M.D.N.C.2006); Glastetter v. Novartis Pharm. Corp., 107 F.Supp.2d 1015, 1027-28 (E.D.Mo.2000); In re Breast Implant Litig., 11 F.Supp.2d 1217, 1229-30 (D.Colo.1998); Hall, 947 F.Supp. at 1412. In such cases, a whole host of potential causal factors — medical, environmental, occupational — may be implicated, such that the connection between the accused product and resulting injury is not readily apparent, if not tenuous. Depending on the specific facts of alleged injury and the relevant evidence cited to support causation, the differential diagnosis methodology might well be inappropriate and insufficient to reach Daubert’s reliability threshold for general causation. In other words, “the basis for establishing the scientific validity of a differential diagnosis will vary depending on the type of injury” and whether it involves a “complicated biological explanation,” “a long latency period,” or “the lack of a single sharp exposure event.” Marcum v. Adventist Health System/West, 345 Or. 237, 249, 193 P.3d 1 (Or.2008) (en banc) (citation omitted); see also Heller, 167 F.3d at 154 (the “overall determination” of whether an expert opinion is based on “good grounds” will depend on the strength of case-specific factors such as temporal relationship); In re Ephedra Prods. Liab. Litig., 478 F.Supp.2d 624, 633 (S.D.N.Y.2007). In contrast, plaintiffs allege the localized injury of glenohumeral chondrolysis after anesthetics were continuously and directly infused into their shoulder joints — a part of the human body that is encased and has no blood supply. Further, plaintiffs and other patients developed chondrolysis within a relatively short time after arthroscopies with continuous infusion, and reports of chondrolysis increased dramatically after physicians began administering local anesthetics via pain pumps. Thus, not only does a direct physical correlation exist between the point of exposure and the resulting injury to the shoulder joint, there is an appreciable temporal relationship between the exposure to continuous infusion and the development of chondrolysis. See Best, 563 F.3d at 180-81 (finding differential diagnosis admissible regarding cause of loss of smell because of temporal proximity to chemical exposure and evidence that accused chemical caused mucous membrane irritation); Westberry, 178 F.3d at 262 (admitting expert testimony based on differential diagnosis despite lack of “studies showing that talc, at any threshold level, causes sinus disease”); Perkins v. Origin Medsystems, Inc., 299 F.Supp.2d 45, 58-61 (D.Conn.2004) (finding differential diagnosis reliable for purposes of establishing general causation where plaintiff alleged pain and injury from placement of surgical tacks). In fact, numerous courts have approved opinions based on differential diagnosis to show general causation, despite the absence of conclusive causal evidence. See Clausen v. M/V New Carissa, 339 F.3d 1049, 1058-59 (9th Cir.2003); Mattis v. Carlon Elec. Prods., 295 F.3d 856, 861 (8th Cir.2002). Turner v. Iowa Fire Equip. Co., 229 F.3d 1202, 1208-09 (8th Cir.2000) (approving differential diagnosis for general causation but finding testimony inadmissible on other grounds); see also Heller, 167 F.3d at 154; Kennedy, 161 F.3d at 1229-30; Zuchowicz v. United States, 140 F.3d 381, 387 (2d Cir.1998); Benedi v. McNeil-P.P.C., Inc., 66 F.3d 1378, 1384 (4th Cir.1995); McCullock v. H.B. Fuller Co., 61 F.3d 1038, 1043-44 (2d Cir.1995); In re Paoli, 35 F.3d at 744; In re Fosamax, 645 F.Supp.2d at 178-79 (a physician need not rely on controlled studies to “rule in” a suspected cause); Yarchak v. Trek Bicycle Corp., 208 F.Supp.2d 470, 499 (D.N.J.2002) (expert testimony on general causation should be admitted when based on a “thorough differential diagnosis [that] reliably flows from the underlying facts of the case”). For example, in Kennedy, the plaintiffs expert Dr. Spindler opined that Zyderm, a collagen product comprised of bovine tissues injected under the skin for a “smoother appearance,” could cause the autoimmune disorder of atypical systemic lupus erythematosus (SLE). 161 F.3d at 1228. Dr. Spindler’s proffered expert testimony was “based on his knowledge of the connection between collagen and various autoimmune disorders, combined with his observation of [the plaintifffs injuries and her medical history and laboratory tests.” Id. at 1229-30. The distinct court excluded Dr. Spindler’s testimony, focusing “on the lack of specific studies proving Zyderm causes lupus, and the absence of consensus in the medical community on this point.” Id. at 1230. The Ninth Circuit reversed, finding that “the district court ignored the scientific studies relied upon by Dr. Spindler that reinforce the validity of the methodology Dr. Spindler relied upon in reaching his conclusion.” Id. In particular, the court noted that Dr. Spindler relied on peer-reviewed studies establishing “that Zyderm induces the body to produce the same autoimmune antibodies that are the hallmark of autoimmune diseases like SLE.” Kennedy, 161 F.3d at 1228. ■ While recognizing that Dr. Spindler’s opinion could be viewed with skepticism, the court nonetheless found Dr. Spindler’s methodology reliable: The fact that a cause-effect relationship betiueen Zyderm and lupus in particular has not been conclusively established does not render Dr. Spindler’s testimony inadmissible .... Dr. Spindler’s analogical reasoning was based on objective, verifiable evidence and scientific methodology of the kind traditionally used by rheumatologists. This is precisely what DaubeH requires. Id. at 1230 (citations omitted) (emphasis added). Although the Ninth Circuit did not employ the terms “differential diagnosis” or “general causation,” such was the methodology employed by Dr. Spindler in asserting a general causation opinion. Id. at 1228 (“Dr. Spindler relied upon a wide variety of objective, verifiable evidence in forming his opinion that Zyderm causes autoimmune disorders such as atypical SLE.”); see also Clausen, 339 F.3d at 1058-60 (holding that “a lack of specific scholarly support” did not prevent the admission of differential diagnosis testimony ruling in oil toxicity as cause of oyster morbidity, where the expert relied on field studies, laboratory studies, history of the oyster site, findings of oil contamination, and the temporal relationship between the oil spill and oyster morbidity). Similar to the facts in Kennedy, plaintiffs’ experts here rely on “objective, verifiable evidence” of in vitro and animal studies demonstrating the ehondrotoxicity of local anesthetics, case series describing an association between continuous infusion and chondrolysis, the temporal relationship between continuous infusion and chondrolysis, and reports of continuous infusion as an isolated or common factor. Cf. Joiner, 522 U.S. at 145-46, 118 S.Ct. 512 (medical evidence relied on was “far removed,” suggested “no link” between exposure and injury, and provided “no grounds for associating” exposure and injury). Given these facts, I find that plaintiffs’ experts need not present conclusive evidence of causation, and that they offer “independently reliable evidence” to rule in continuous infusion as a cause of chondrolysis. Hollander, 289 F.3d at 1210 (citing Zuchowicz, 140 F.3d at 385-87 and Kennedy, 161 F.3d at 1228-30); In re Ephedra, 393 F.Supp.2d at 187-88 (discussing Zuchowicz and McCulloch generally). Finally, I remain unpersuaded by defendants’ reliance on Kilpatrick. There, the district court excluded an expert’s proffered testimony that continuous infusion can cause chondrolysis, because no evidence cited by the expert “proved” causation. Kilpatrick 2009 WL 2058384, at *7-9. In particular, the district court found that the “unsettled” state of the medical literature — the Hansen/Beck Study, the Greis case series, and Gomoll I — was insufficient to establish causation. Id. Further, the district court found that the expert’s reliance on patient records and the medical literature had no “known rate of error.” Id. at *7-9. The court even went so far as to criticize the expert’s failure to account for the 7 of 19 shoulders in the Hansen/Beck Study that received continuous infusion but did not develop chondrolysis, characterizing the expert’s lack of explanation as “an unexplained 40% error rate.” Id. at *5. If 100% of patients receiving continuous infusion must develop chondrolysis before an expert may reliably opine on causation, expert testimony would hardly be necessary. Given that the court did not cite statistical or epidemiological evidence in assessing a “40% error rate,” one can only surmise that it was the court’s own finding, one made without evidentiary support. However, Rule 702 imposes on the court neither “the obligation” nor “the authority to become [an] amateur seientist[] in order to perform” its gatekeeping role. See Daubert, 509 U.S. at 600-01, 113 S.Ct. 2786 (Rehnquist, C.J., concurring in part). I find that the district court in Kilpatrick went far beyond its gatekeeping function and “failed to distinguish between the threshold question of admissibility of expert testimony and the persuasive weight to be accorded such testimony by a jury.” Kennedy, 161 F.3d at 1228. Importantly, it is not the court’s role to decide whether the proffered expert testimony sufficiently proves that continuous infusion can cause chondrolysis; rather, it is the court’s duty to ensure that the proffered expert testimony is sufficiently reliable to be admitted at trial for consideration by the trier of fact. “Under Daubert, the district judge is ‘a gatekeeper, not a fact finder.’ ” Primiano, — F.3d at-, 2010 WL 1660303, at *4 (quoting United States v. Sandoval-Mendoza, 472 F.3d 645, 654 (9th Cir. 2006)). In keeping with the court’s proper role and the “liberal thrust” of Rule 702, I will not exclude plaintiffs’ expert testimony simply because the evidence supporting it does not establish causation to a scientific or medical certainty. Daubert, 509 U.S. at 588,113 S.Ct. 2786. B. Sufficiency of Facts and Data Supporting General Causation Defendants punctuate the lack of epidemiological studies on chondrolysis and maintain that plaintiffs’ experts impermissibly extrapolate causal connections from in vitro studies, animal studies, and case series, such that the “analytical gap” between the medical evidence and them opinions grows too wide to meet the reliability threshold of Rule 702. Defendants further argue that plaintiffs’ experts unsuccessfully attempt to fill the “gaps” between the medical evidence and their opinions through generalized references to the whole of medical evidence. 1. Epidemiological Evidence Plaintiffs’ experts do not cite an epidemiological study in support of their general causation opinions, to defendants, a “fatal evidentiary flaw” that precludes expert testimony on general causation. Defendants argue that without a prospective, controlled epidemiological study to establish the background rate and relative risk of chondrolysis in the general population, plaintiffs’ experts’ opinions are merely “untested hypothes[e]s” unsupported by “good science.” Hall, 947 F.Supp. at 1401-02. Plaintiffs respond that epidemiological evidence is not necessary to support their claims. Nonetheless, plaintiffs contend that statistical analysis of the Hansen/Beck Study provides sufficient epidemiological evidence of the background rate and relative risk of chondrolysis for purposes of general causation. The Hansen/Beck Study reported surgical results of 152 shoulder arthroscopies. Pain pumps were inserted in 19 shoulder joints to deliver a continuous infusion of local anesthetics, and 12 of those, or 63%, developed chondrolysis. Hansen/Beck Study, p. 1632. Patients who were not exposed to the continuous infusion did not develop chondrolysis, and the authors found no common factor in patients with chondrolysis except their exposure to continuous infusion. Id. Plaintiffs experts’ Dr. Sander Greenland, an epidemiologist, and Dr. Martin Wells, a bio-statistician, opine that the Hansen/Beck Study, though published as a case series, is comprised of retrospective cohort data comparing the occurrence of chondrolysis in two patient populations — those who were exposed to continuous infusion and those who were not. Based on their analysis, they assert that the high association between continuous infusion and chondrolysis reflected in the Hansen/Beck Study is statistically significant and cannot be attributed to chance. Defendants dispute the characterization of the Hansen/Beck Study as an epidemiological cohort study. “Epidemiology is the field of public health and medicine that studies the incidence, distribution, and etiology of disease in human populations. The purpose of epidemiology is to better understand disease causation and to prevent disease in groups of individuals.” Reference Manual, p. 335. Epidemiology thus focuses on general rather than specific causation. Id. at 336. While “epidemiologic evidence can justify an inference that an agent causes a disease,” id. at 336 n. 8, “epidemiology cannot objectively prove causation; rather, causation is a judgment for epidemiologists and others interpreting the epidemiologic data.” Id. at 374. An epidemiological cohort study involves the study of two populations — or “cohorts” — to determine whether a population exposed to a particular agent is more likely to develop disease than the population which was not exposed. Id. at 340, 389. A retrospective cohort study occurs where “the researcher gathers historical data about exposure and disease outcome of the exposed cohort.” Id. at 340 n. 19. The possibility of bias and error is generally minimized through study design, usually developed before data is gathered, and involves selection of the study group under defined criteria. Id. at 341, 364, 371. A cohort study is considered Level II scientific evidence, while a case series is considered Level IV. It is undisputed that Dr. Beck did not design the Hansen/Beck Study as a Level II retrospective cohort and did not account for selection bias or confounding factors. Greenland Dep., Sept. 24, 2009, p. 48 (“In fact, I know [Hansen and Beck] didn’t take any procedures to try and adjust for possible selection bias.”). Dr. Beck did not conduct epidemiological or statistical analysis, he did not consult with an epidemiologist, and he did not intend to “perform a Level II paper.” Beck Dep., Aug. 31, 2009, p. 450. Rather, Dr. Beck reported on the occurrences of chondrolysis in his patients and “presented them for the review.” Beck Grossnickle testimony, Mar. 3, 2009, Vol. 5B, p. 1225. In other words, the Hansen/Beck Study was not designed as a “highly rigid, highly scientific study of A versus B.” Id. In fact, Dr. Beck considers his study to be a Level IV case series, and it was published as such after a peer-review process. Beck Dep., Aug. 31, 2009, p. 445 (stating he had “no quarrel” with the Hansen/Beck Study published as a Level IV case series. “It is what it is.”). Several experts in this litigation also consider the Hansen/Beck Study a Level IV case series. Although Drs. Greenland and Wells claim the Hansen/Beck Study data is similar to a Level II cohort, neither of them analyzed the underlying data of the study or performed independent analysis of potential biases or confounding factors. See Greenland Dep., Sept. 24, 2009, p. 91, 167-68. Further, Drs. Greenland and Wells both admit that the high association they discerned is limited to the patient population in the Hansen/Beck Study and cannot be generalized or applied to other patient populations who were exposed to continuous infusion. Finally, Dr. Greenland testified that the biggest limitation of the Hansen/Beck Study was its emphasis on continuous infusion without considering other potential causes of chondrolysis. Transcript of Proceedings, Nov. 18, 2009, p. 183, 212-13, 216-17; see also Wells Dep., Oct. 5, 2009, p. 48-49. Thus, I find it questionable whether the Hansen/Beck Study constitutes helpful or relevant epidemiological evidence to support an opinion of general causation between continuous infusion and chondrolysis. Regardless, the lack of epidemiological evidence is not fatal to the admission of plaintiffs’ experts’ testimony, particularly in a case where no epidemiology “rules out” continuous infusion as a cause of chondrolysis. See W.R. Grace, 504 F.3d at 765 (“[T]he fact that a study is associational — rather than an epidemiological study-intended to show causation — does not bar it from being used to inform an expert’s opinion____”); Norris, 397 F.3d at 882 (epidemiological studies are not always necessary); Glastetter v. Novartis Pharm. Corp., 252 F.3d 986, 992 (8th Cir.2001) (accord); Kennedy, 161 F.3d at 1229 (finding expert’s opinion reliable despite the lack of epidemiological studies linking Zyderm to atypical SLE); Grant v. Pharmative, 452 F.Supp.2d 903, 908 (D.Neb.2006); In re Ephedra, 393 F.Supp.2d at 189-90 (explaining that “the absence of definitive scientific studies” should not “deprive a jury of having before it scientific opinions,” though “less definitive and more qualified”); In re Phenylpropanolamine (PPA) Prods. Liab. Litig., 289 F.Supp.2d 1230, 1242 (W.D.Wash.2003) (“Non-epidemiological sources are frequently utilized by experts in rendering scientific opinions and, under Daubert, should be considered by the court in assessing the reliability of those opinions.”). Further, “ ‘[t]he human body is complex, etiology is often uncertain, and ethical concerns often prevent double-blind studies to calculate statistical proof.’ ” Primiano, — F.3d at-, 2010 WL 1660303, at *5 (quoting Sandovalr-Mendoza, 472 F.3d at 655). It is undisputed that chondrolysis is a rare disease, with few people exposed to potential causes and fewer actually developing the disease; consequently, “the opportunities for scholarly research are few. In such a situation, a lack of published studies should not bar otherwise scientifically valid testimony.” Clausen, 339 F.3d at 1060. Moreover, ethical considerations preclude randomized, controlled epidemiological studies of continuous infusion given the potential for irreversible harm. Basamania Dep., Aug. 15, 2009, p. 434 (“[Tjhere will be no [prospective Level I, II, or III, studies] because it would not be ethical to perform those studies based on what we know from our Level IV evidence.”). Therefore, while epidemiological evidence is significant and can be helpful, it is not necessary to establish general causation. 2. Medical Studies Supporting Causation Opinions Plaintiffs’ experts universally rely on in vitro and animal studies demonstrating the chondrotoxic effects of local anesthetics and case series associating continuous infusion with chondrolysis. Defendants argue that plaintiffs’ experts impermissibly extrapolate causal facts from these studies in a flawed attempt to support general causation. a. In Vitro and Animal Studies Defendants take issue with several in vitro and animal studies cited by plaintiffs’ experts, including those conducted by Drs. Dogan, Chu, Dragoo, Karpie, Gomoll, and Lo. Dr. Dogan conducted animal studies involving the effects of bupivaeaine when injected into the articular cartilage and synovium membranes of rabbit knee joints. Dogan, p. 513. Dr. Dogan observed “histopathological changes” to the joint and suggested that “physicians should be cautious when administering intra-artieular bupivaeaine.” Id. at 518. In her first study, Dr. Chu assessed the laboratory effects of 0.5% bupivaeaine on bovine articular chondrocytes and found that such dosage was “cytotoxic” to bovine chondrocytes after 15 to 30 minutes of exposure. Dr. Chu concluded that while “the effects of bupivaeaine on human cartilage may differ from the results obtained in vitro with bovine tissue, these results suggest that caution is needed in the intraarticular use of 0.5% bupivaeaine solution.” Chu I, p. 697. In her second study, Dr. Chu found that prolonged, continuous doses of bupivaeaine increased the toxicity to human and bovine articular chondrocytes and asserted that “intra-articular bupivacaine should be used at the lowest dosage and for the shortest period of time necessary.” Chu II, pp. 818-20. Dr. Karpie, with Dr. Chu, conducted an in vitro study of bovine articular chondrocytes after exposure to lidocaine and found that “[ajlthough lidocaine chondrotoxicity was less than previously reported with bupivacaine, these data suggest a negative class effect of local anesthetics on articular chondrocyte viability.” Karpie, p. 1626. Ms. Piper and Dr. Kim studied the effects of bupivacaine and ropivacaine on human articular chondrocytes. The results of their study “demonstrate that a thirty-minute exposure to 0.5% bupivacaine is cytotoxic to human articular chondrocytes,” both in intact cartilage and in cultured chondrocytes. Piper, pp. 989-90. Similarly, Dr. Dragoo conducted research on the effects of bupivacaine on human cartilage cells harvested from patients undergoing knee replacement surgery. Dr. Dragoo noted that “[ajlthough a direct link of anesthetic-induced chondrolysis has not been established, multiple studies have shown the detrimental effects of local anesthetics on chondrocyte viability.” Dragoo, p. 1484. Dr. Dragoo’s study showed “significant loss of chondrocyte viability at all time points with medications containing epinephrine,” particularly when exposed to 0.5% bupivacaine for 72 hours. Dragoo, p. 1487. Dr. Lo analyzed the chondrotoxic effects of local anesthetics through the use of a bovine disk model. Dr. Lo concluded that local anesthetics such as bupivacaine can have “a detrimental effect on chondrocyte viability in a time and dose-dependent manner.” Lo, pp. 709, 712, 714. Finally, Dr. Gomoll conducted two animal studies on the toxic effects of bupivacaine injected into rabbit shoulder joints. In his 2006 study, Dr. Gomoll found that “[cjontinuous intra-articular infusion of bupivacaine with and without epinephrine led to significant histopathologic and metabolic changes in articular cartilage.” Gomoll I, p. 818. “In particular, bupivacaine showed profound chondrotoxic effects in an experimental model that closely followed the current clinical application of postoperative pain pumps.” Id. In his 2009 study, Dr. Gomoll found “no permanent impairment of cartilage function” three months after intra-articular infusion of bupivacaine in the rabbit shoulder model, although “20% to 30% of chondrocytes appeared nonviable 1 week after infusion with bupivacaine.” Gomoll II, pp. 75-76. Defendants maintain that plaintiffs’ experts cannot reliably extrapolate data from these in vitro and animal studies to demonstrate causation in humans, particularly when the findings of the studies do not espouse a causal connection between continuous infusion and chondrolysis. See In re Bausch & Lomb, Inc. Contact Lens Solution Prods. Liab. Litig., 2009 WL 2750462, at *12 (D.S.C. Aug. 26, 2009) (“In vitro tests generate hypotheses but lack sufficient reliability, standing alone, to demonstrate causation in humans.”). Defendants emphasize that the studies’ authors themselves cautioned against extrapolating the results to humans in a clinical setting. However, “analogy, inference and extrapolation can be sufficiently reliable” when the expert’s opinion is the “kind that a reasonable scientist or physician would make in a decision of importance arising in the exercise of his profession outside the context of litigation.” In re Ephedra, 393 F.Supp.2d at 189. Without question, physicians consider “the medical and scientific literature as well as information about a patient’s condition to best determine causality.” Reference Manual, p. 470; Metabolife Int’l, Inc. v. Wornick, 264 F.3d 832, 842 (9th Cir.2001) (noting that animal studies can provide “useful data about human health.”). In fact, many of the peer-reviewed articles cited by plaintiffs and their experts include discussions of in vitro and animal studies, including those conducted by Dr. Chu and Dr. Gomoll. Several articles not only cite Dr. Chu’s studies, but give credence to the correlation between chondrocyte damage and exposure to local anesthetics. See, e.g., Greis, p. 1343; see also Hopkins v. Dow Corning, Corp., 33 F.3d 1116, 1125 (9th Cir.1994) (finding admissible testimony based on scientific studies and “corroborating evidence found in studies conducted on animals”); In re Silicone Gel Breast Implants Prods. Liab. Litig., 318 F.Supp.2d 879, 910-11 (C.D.Cal.2004) (noting reliance by researchers and agencies on relevant animal studies). Thus, defendants cannot credibly argue that the reliance on in vitro and animals studies is scientifically invalid in this ease. Whatever inadequacies arise from extrapolation will no doubt be addressed through vigorous cross-examination by defense counsel. I further find that the cited in vitro and animal studies lend support to the opinions of plaintiffs’ experts by establishing the chondrotoxicity of local anesthetics. Such toxicity is significant given that chondrolysis results from the degeneration and eventual death of cartilage cells. Solomon, p. 1330. Granted, plaintiffs’ experts are not certain why bupivacaine is chondrotoxic or how the damage is caused, though some opine that displacement of the synovial fluid robs the cartilage matrix of nutrients necessary for its renewal. See infra, pp. 1130, 1133-34. However, “[n]ot knowing the mechanism whereby a particular agent causes a particular effect is not always fatal to a plaintiffs claim. Causation can be proved even when we don’t know precisely how the damage occurred, if there is sufficiently compelling proof that the agent must have caused the damage somehow.” Daubert II, 43 F.3d at 1314; Domingo ex rel. Domingo v. T.K., 289 F.3d 600, 607 (9th Cir.2002) (“[I]t is not necessary to show how a particular act or event caused an injury.”); see also Primiano, — F.3d at -, 2010 WL 1660303, at *5 (“Lack of certainty is not, for a qualified expert, the same thing as guesswork.”); In re Neurontin Mktg. Sales Practices & Prods. Liab. Litig., 612 F.Supp.2d 116, 149 (D.Mass.2009) (“biologic plausibility” supported opinion on causation despite “robust debate in the scientific community” on the proposed mechanism); In re PPA, 289 F.Supp.2d at 1247 (“The fact that the mechanism remains unclear does not call the reliability of the opinion into question.”). The cited studies also demonstrate a basic dose-response relationship in that higher doses and longer exposure to bupivacaine result in increased chondrotoxicity. See Chu I, pp. 693, 696; Chu II, pp. 814, 818-20; Dragoo, pp. 1487-88; see also Badylak Dep. July 27, 2009, pp. 328, 349 (“I think everybody would agree the higher the dose and the longer exposure, the worse you’re going to get. So we understand the relationship to be dose depend— dose and time dependent. What we don’t know is what the — the threshold is. We don’t know what — what’s too much.”). While plaintiffs’ experts cannot identify the precise threshold dose of bupivacaine or the length of exposure that triggers irreparable chondrocyte damage, “Daubert does not require that every aspect of a theory of medical causation be supported by research on the identical point.” Domingo, 289 F.3d at 607 (quotation marks and citation omitted); see also Westberry, 178 F.3d at 264 (the precise “exposure necessary to cause specific harm to humans” is not “always available, or necessary, to demonstrate” toxicity and “need not invariably provide the basis for an expert’s opinion on causation”) (quoted with approval in Clausen, 339 F.3d at 1058-59). Defendants next argue that plaintiffs’ experts failed to reconcile their opinions with Gomoll II. Defendants are not entirely correct. In particular, Dr. Badylak, when asked if Gomoll II did not support the finding that local anesthetics were chondrotoxic, explained: Oh no, I — -just the opposite. It is chondrotoxic. What [Gomoll’s] 2000 — his 2006 study showed it was chondrotoxic, so he did the 2009 study to — to look for longer terms. He doesn’t change his opinion that it’s not chondrotoxic. What he says in the 2009 [study] is that in the model that was used, which was [sic] these young rabbits, that perhaps a reparative response was — -was taking place and that we should not necessarily extrapolate that to humans. Badylak Dep. July 27, 2009, p. 286; see also Dragoo Dep., June 12, 2009 pp. 207-OS, 228 (explaining that rabbits can regenerate cartilage tissue). Whether other physicians, such as Dr. Basamania, interpret Gomoll II differently is properly addressed on cross-examination. See Basamania Dep., Aug. 15, 2009, p. 474. I recognize that, as Dr. Badylak conceded, in vitro and animal studies are not “perfect.” Badylak Dep., July 27, 2009, p. 287 (“There is — until you do the human clinical trial, you just never know.”). However, such studies are relied on in the medical profession and provide useful information, as Dr. Dragoo explained: [B]y ethical standards, we cannot [test for the chondrotoxicity of local anesthetics] in [a live] human model. So therefore, we will use an animal model, and therefore, we would have to extrapolate to say that the animal models are a good