According to her biographies[1], Madge Thurlow Macklin excelled in mathematics, graduated from Goucher College, received a fellowship to study physiology at Johns Hopkins University, and then went on graduate with honors from the Johns Hopkins Medical School, in 1919.  Along the way, she acquired a husband, Charles C. Macklin, an associate professor of anatomy at Hopkins, and had her first child.

In 1921, the Macklins moved to London, Ontario, to take positions at the University of Western Ontario.  Charles received an appointment as a professor of histology and embryology, and went on to distinguish himself in pulmonary pathology. Madge Macklin received an appointment as a part-time instructor at Western, but faced decades of resistance because of her sex and her marriage to a professor. She was never promoted beyond part-time assistant professor, at Western.

Despite the hostile work environment, Madge Macklin published and lectured on statistical and medical genetics.  Her papers made substantial contributions to the inheritable aspects of human cancer and other diseases.

Macklin advocated tirelessly for the inclusion of medical genetics in the American medical school curriculum. See, e.g., Marge T. Macklin, “Should The Teaching Of Genetics As Applied To Medicine Have A Place In The Medical Curriculum?” 7 J. Ass’n Am. Med. Coll. 368 (1932); “The Teaching of Inheritance of Disease to Medical Students: A Proposed Course in Medical Genetics,” 6 Ann. Intern. Med. 1335 (1933). Her advocacy largely succeeded both in medical education and in the recognition of the importance of genetics for human diseases.

Macklin’s commitment to medical genetics led her to believe that physicians had a social responsibility to engage in sensible genetics counseling, and reasonable guidance on procreation and birth control. In 1930, Macklin helped found the Eugenics Society of Canada, and went on to serve as its Director in 1935. Her writings show none of the grandiosity or pretensions that lie in creating a master race, as much as avoiding procreation among imbeciles. See, e.g., Madge Macklin, “Genetical Aspects of Sterilization of the Mentally Unfit,” 30 Can. Med. Ass’n J. 190 (1934).

Some of her biographers suggest that Macklin lost her position at Western due to her views on eugenics, and others suggest that her trenchant criticisms of the inequity of the University’s sexism led her to go to Ohio State University in 1946, as a cancer researcher, funded by the National Research Council. Macklin taught genetics at Ohio State, something that Western never permitted her to do. In 1959, three years before her death, Macklin was elected president of the American Society for Human Genetics.

By all accounts, Macklin was an extraordinary woman and a gifted scientist, but my interest in her work stems from her recognition in the 1930s and 1940s, for the need for greater rigor in drawing etiological inferences in medical science.  Well ahead of her North American colleagues, Macklin emphasized the need to rule out bias, confounding, and chance before accepting apparent associations as causal. She wrote with unusual clarity and strength on the subject, decades before Sir Austin Bradford Hill. Her early mathematical prowess served her well in rebutting case reports and associations that were often embraced uncritically.

 *  *  *  *  *  *  *

In 1939, Professor Max Klotz of the University of Toronto, reported a very crude analysis from which he inferred a putative association between silicosis and lung cancer. Max O. Klotz, “The Association of Silicosis and Carcinoma of the Lung, 35 Am. J. Cancer 38 (1939). Klotz was a pathologist, and he worked with autopsy series, without statistical tools or understanding, as was common at the time. Macklin wrote a thorough refutation, which amply illustrates her abilities and her clear thinking:

“Another type of improper control for analysing cancer data arises through ignoring the fact that every cancer has a specific age incidence, and sex predilection. I have already mentioned breast, uterine and prostatic cancers, but other types of cancer, not of the generative organs,  have marked sex predilection. Cancer of the lung is a good example. It occurs four times as frequently in the male as in the female. If we desire to make any study of causative factors in lung cancer we must be sure that our control group is comparable to our experimental group. Again I will take an example from the literature. A worker was investigating the possible role of silicosis in inducing lung cancer. He compared the incidence of lung cancer in a group of 50 cases of silicosis, and in a large necropsy group of 4500 ‘unselected’ cases from a general hospital. He found that lung cancer was 7 times as frequent in the silicosis group as in the unselected necropsies. This is an excellent example of misunderstanding as to what is meant by ‘random’ sample. Because the 4500 necropsies were ‘unselected’ the worker thought that he had a good control group. As a matter of fact, in order to have a good control, he needed to select very carefully from these 4500 necropsies, those which he was to use as his standard. He forgot two things:

(1) that lung cancer is 4 times as common in the male as in the female and that all his silicosis cases were males, therefore his unselected necropsies should have been highly selected to contain only males. Assuming that half of his 4500 necropsies were females, and that among them one fifth of the lung cancers occurred, one can easily show that had his control group been all males as was his silicosis group, lung cancer would have been only 4.8 times as common among the silicosis patients as among the general necropsy group instead of 7 times as he found it.

(2) The second thing he forgot is that silicosis does not develop until 15 or 20 years of exposure have passed by. That placed all his silicosis patients in the late forties or early fifties, just when lung cancer becomes most common. Many of his general necropsy group were in the age range below 45, hence not in the lung cancer age. He should have selected only those males from the necropsy group who matched the age distribution of his silicosis patients. If he then found a significantly higher percentage of lung cancer among his silicosis patients he could have suggested a relationship between the two. Until that control group is properly studied, his results are valueless.”

****

SUMMARY

* * *

“The second point to be noted is that the control group should correspond as nearly as possible in all respects with the group under investigation, with the single exception of the etiologic factor being investigated. If silicosis is being considered as a causative agent in lung cancer, the control group should be as nearly like the experimental or observed group as possible in sex, age distribution, race, facilities for diagnosis, other possible carcinogenic factors, etc. The only point in which the control group should differ in an ideal study would be that they were not exposed to free silica, whereas the experimental group was. The incidence of lung cancer could then be compared in the two groups of patients.

This necessity is often ignored; and a ‘random’ control group is obtained for comparison on the assumption that any group taken at random is a good group for comparison. Fallacious results based on such studies are discussed briefly.”

Madge Thurlow Macklin, “Pitfalls in Dealing with Cancer Statistics, Especially as Related to Cancer of the Lung,” 14 Diseases Chest 525 532-33, 529-30 (1948).

The recognition that uncontrolled, or improperly controlled, research was worthless was a great advance in thinking about medical causation.  In the 1940s, Macklin was ahead of her time; indeed, if she were alive today, she would be ahead of many contemporary epidemiologists.

——

[1]Barry Mehler, “Madge Thurlow Macklin,” from Barbara Sicherman and Carl Hurd Green, eds., Notable American Women: The Modern Period 451-52 (1980); Laura Lynn Windsor, Women in Medicine: An Encyclopedia 134 (2002).

 

 

 

 

 

 

ITERATIVE DISJUNCTIVE SYLLOGISM

Basic propositional logic teaches that the disjunctive syllogism (modus tollendo ponens) is a valid argument, in which one of its premises is a disjunction (P v Q), and the other premise is the negation of one of the disjuncts:

P v Q

~P­­­_____

∴ Q

See Irving Copi & Carl Cohen Introduction to Logic at 362 (2005). If we expand the disjunctive premise to more than one disjunction, we can repeat the inference (iteratively), eliminating one disjunct at a time, until we arrive at a conclusion that is a simple, affirmative proposition, without any disjunctions in it.

P v Q v R

~P­­­_____

∴ Q v R

~Q­­­_____

∴ R

Hence, the term, “iterative disjunctive syllogism.” Fans of Sir Arthur Conan Doyle will recognize that iterative disjunctive syllogism is nothing other than the process of elimination, as explained by Doyle’s fictional detective, Sherlock Holmes. See, e.g., Doyle, The Blanched Soldier (“…when you have eliminated all which is impossible, then whatever remains, however improbable, must be the truth.”); Doyle, The Beryl Coronet (“It is an old maxim of mine that when you have excluded the impossible, whatever remains, however improbable, must be the truth.”); Doyle, The Hound of the Baskervilles (1902) (“We balance probabilities and choose the most likely. It is the scientific use of the imagination.”); Doyle, The Sign of the Four, ch 6 (1890)(“‘You will not apply my precept’, he said, shaking his head. ‘How often have I said to you that when you have eliminated the impossible, whatever remains, however improbable, must be the truth? We know that he did not come through the door, the window, or the chimney. We also know that he could not have been concealed in the room, as there is no concealment possible. When, then, did he come?”)

The process of elimination sometimes surfaces in court cases in which expert witnesses attempt to attribute a health outcome in a specific person to that person’s prior environmental, occupational, or lifestyle exposures.  A few general conclusions can be advanced about this mode of reasoning:

1. Differential Etiology NOT Differential Diagnosis

Although courts and expert witnesses sometimes refer to this process of ruling out as “differential diagnosis,” their terminology is a misnomer.  Their usage is not an innocent diction error because diagnosis is almost never involved, and the usage attempts to suggest that the causal attribution is part of a process typically conducted by a treating physician, when in fact, the treating physician rarely determines the actual cause in the person. Etiology is usually not needed to determine the nature of the disease or the proper course of treatment. Biomarkers, other than diagnostic criteria, rarely point to a specific cause(s) in a given case. The “differential diagnosis” misnomer tends to obscure clear reasoning about physician witnesses, who are often not experts in epidemiology or other sciences needed to assess general causation, not familiar with systematic reviews, not published on the scientific issue of general causation.  The specific causal attribution is analogous to differential diagnosis, in its process of ruling in, and then ruling out, and therefore is sometimes called differential etiology. See, e.g., Michael D. Green, D. Michal Freedman, and Leon Gordis, Reference Guide on Epidemiology 549, 617 & n.211, in Reference Manual on Scientific Evidence (3ed ed. 2011)[RMSE].

2. Differential Etiology Assumes, and Cannot Establish, General Causation

The differential etiology process assumes that each disjunct – each putative specific cause – has itself been established as a known cause of the disease in general. Id. at 618 (“Although differential etiologies are a sound methodology in principle, this approach is only valid if general causation exists … .”). In the case of a novel putative cause, the case may give rise to a hypothesis that the putative cause can cause the outcome, in general, and did so in the specific case.  That hypothesis must, of course, then be tested and supported by appropriate analytical methods before it can be accepted for general causation and as a putative specific cause in a particular individual.

3.  Differential etiology typically fails when a substantial percentage of cases are idiopathic in origin

When one of the disjuncts is “no known cause,” then it will be virtually impossible to negate and remove from the disjunction. If very few cases have idiopathic causes, the error rate may be low, and tolerable. Take for example, asbestosis, a diffuse interstitial lung disease caused by chronic, excessive inhalation of asbestos.  Clinically asbestosis will look similar to idiopathic pulmonary fibrosis (IPF), a lung disease of unknown origin.  IPF may remain a differential diagnosis in every case because it cannot be ruled out, clinically.  The likelihood of IPF, however, will be relatively low in a cohort of asbestos miners, and thus not a serious source of error.  In a study of household exposure cases, in which the exposure resulted from a family member’s bringing home dust from work, IPF may be a much likelier alternative, and the failure to rule it out may invalidate conclusions about the asbestosis diagnosis in every case in the cohort.

With respect to differential etiology, the same principle applies: the iterative disjunctive syllogism requires ruling out “unknown,” or at least minimizing the number of cases in the unknown disjunct that are not ruled out.  See RMSE at 618 (“Although differential etiologies are a sound methodology in principle, this approach is only valid if … a substantial proportion of competing causes are known. Thus, for diseases for which the causes are largely unknown, such as most birth defects, a differential etiology is of little benefit.”)(internal citations omitted). Accordingly, many cases reject proffered expert witness testimony on differential etiology, when the witnesses fail to rule out idiopathic causes in the case at issue. What is a substantial proportion?  Unfortunately, the RMSE does not attempt to quantify or define “substantial.” The inability to rule out unknown etiologies remains the fatal flaw in much expert witness opinion testimony on specific causation.

More Nonsense on Differential Diagnosis

The Supreme Court recently addressed differential etiology in Matrixx Initiatives, in stunningly irrelevant and errant dicta:

“We note that courts frequently permit expert testimony on causation based on evidence other than statistical significance. See, e.g., Best v. Lowe’s Home Centers, Inc., 563 F. 3d 171, 178 (6^th Cir 2009); Westberry v. Gislaved Gummi AB, 178 F. 3d 257, 263–264 (4^th Cir. 1999) (citing cases); Wells v. Ortho Pharmaceutical Corp., 788 F. 2d 741, 744–745 (11^th Cir. 1986). We need not consider whether the expert testimony was properly admitted in those cases, and we do not attempt to define here what constitutes reliable evidence of causation.”

Matrixx Initiatives, Inc. v. Siracusano, 131 S. Ct. 1309, 1319 (2011).  The citation to Wells was clearly wrong in that the plaintiffs in that case had, in fact, relied upon studies that were nominally statistically significant, and so the Wells court could not have held that statistical significance was unnecessary.[1]

The two other cases cited by the Supreme Court, however, were both about “differential diagnosis,” and had nothing to do with statistical significance.  Both cases assumed that general causation was established, and inquired into whether expert witnesses could reasonably attribute the health outcome in the case to the exposures that were established causes of such outcomes.  The Court’s selection of these cases, quite irrelevant to its discussion, appears to have come from the Solicitor General’s amicus brief in Matrixx.[2]

Although cited for an irrelevant proposition, the Supreme Court’s selection of the Best’s case was puzzling because the Sixth Circuit’s discussion of the issue is particularly muddled. Here is the relevant language from Best:

“[A] doctor’s differential diagnosis is reliable and admissible where the doctor

(1) objectively ascertains, to the extent possible, the nature of the patient’s injury…,

(2) ‘rules in’ one or more causes of the injury using a valid methodology,

and

(3) engages in ‘standard diagnostic techniques by which doctors normally rule out alternative causes” to reach a conclusion as to which cause is most likely’.”

Best v. Lowe’s Home Centers, Inc., 563 F.3d 171, 179, 183-84 (6th Cir. 2009).

Of course, a physicians rarely use this iterative process to arrive at causes of diseases in an individual; they use it to identify the disease or disease process that is responsible for the patient’s signs and symptoms. See generally Harold C. Sox, Michael C. Higgins, and Douglas K. Owens, Medical Decision Making (2d ed. 2014).  The Best court’s description does not make sense in that it characterizes the process as ruling in “one or more” causes, and then ruling out alternative causes.  If an expert had ruled in only one cause, then there would be no need or opportunity to rule out an alternative cause.  If the one ruled-in cause was ruled out for other reasons, then the expert witness would be left with a case of idiopathic disease.[3]

We can take some solace in the Supreme Court’s disclaimer that it was not attempting reliable evidence of causation. Differential etiology, however, is irrelevant to general causation, which is the context in which statistical significance arises.  The issue of statistical significance was not addressed; nor could it have been addressed in either Best or Westberry.

What follows is an incomplete selection of cases on differential etiology, good and bad.

Differential Etiology for Specific Causation

FIRST CIRCUIT

Baker v. Dalkon Shield Claimaints Trust, 156 F.3d 248, 252-53 (1st Cir. 1998) (stating that “ ‘differential diagnosis’ is a standard medical technique”)

District Courts within 1st Circuit

Whiting v. Boston Edison Co., 891 F. Supp. 12, 21 n.41 (D. Mass. 1995) (noting that differential diagnosis cannot be used to support conclusion of specific causation when 90% disease cases are idiopathic)

Polaino v. Bayer Corp., 122 F. Supp. 2d 63, 70 & n.7 (D. Mass. 2000) (“differential diagnosis is a useful means of distinguishing one disease from another with similar symptoms, it is not a technique typically used to investigate the cause of an illness”)

Plourde v. Gladstone, 190 F. Supp. 2d 708, 722-723 (D. Vt. 2002) (excluding testimony where expert failed to rule out causes of plaintiff’s illness other than exposure to herbicides)

Allen v. Martin Surfacing, 263 F.R.D. 47, 56 (D. Mass. 2008) (admitting general and specific causation testimony of ALS, to be tested by adversary process, rather than excluded altogether, despite paucity of epidemiologic evidence)

Milward v. Acuity Specialty Products Group, Inc., Civil Action No. 07–11944–DPW, 2013 WL 4812425 (D. Mass. Sept. 6, 2013)

SECOND CIRCUIT

McCullock v. H.B. Fuller Co., 61 F.3d 1038, 1043–44 (2d Cir.1995) (defining differential etiology as an analysis “which requires listing possible causes, then eliminating all causes but one”) (affirming admission of a treating doctor’s testimony despite his inability to “point to a single piece of medical literature that says glue fumes cause throat polyps”) (upholding admission of treating physician who relied upon his “care and treatment of McCullock; her medical history (as she related it to him and as derived from a review of her medical and surgical reports); pathological studies; review of [Defendant] Fuller’s [Material Safety Data Sheet], his training and experience, use of a scientific analysis known as differential etiology (which requires listing possible causes, then eliminating all causes but one); and reference to various scientific and medical treatises”)

United States v. Zuchowitz, 140 F.3d 381, 385-87 (2d Cir. 1998) (“[d]isputes as to . . . faults in [the] use of differential etiology as a methodology, or lack of textual authority for [an] opinion, go to the weight, not the admissibility of [the] testimony”)

Wills v. Amerada Hess Corp., 379 F. 3d 32, 45-46 (2d Cir. 2004)(noting that expert witness failed to account for other possible causes), cert. denied, 126 S.Ct. 355 (2005)

Ruggiero v. Warner-Lambert Co., 424 F.3d 249, 254 (2d Cir. 2005) (“Where an expert employs differential diagnosis to ‘rule out other potential causes’ for the injury at issue, he must also ‘rule in the suspected cause’ and do so using ‘scientifically valid methodology’.”) (quoting Cavallo v. Star Enter., 892 F. Supp. 756, 771 (E.D. Va. 1995), aff’d on this ground, rev’d on other grounds, 100 F.3d 1150 (4th Cir. 1996))

District Courts within 2d Circuit

Becker v. National Health Products, 896 F.Supp. 100 (N.D.N.Y. 1995).

Mancuso v. Consolidated Edison Co. of New York, Inc., 967 F. Supp. 1437, 1450 (S.D.N.Y. 1997)(“it is improper for an expert to presume that the plaintiff ‘must have somehow been exposed to a high enough dose to exceed the threshold [necessary to cause the illness], thereby justifying his initial diagnosis.’ This is circular reasoning.”)

Zwillinger v. Garfield Slope Hous. Corp., 1998 WL 623589, at *20 (E.D.N.Y. Aug. 17, 1998) (excluding testimony and granting summary judgment where expert failed to rule out alternative causes of plaintiff’s immunotoxicity syndrome)

Prohaska v. Sofamor, S.N.C., 138 F. Supp. 2d 422, 439 (W.D.N.Y. 2001) (excluding expert’s opinion and granting summary judgment where expert “was unable to rule out, to a reasonable degree of medical certainty, [plaintiff’s] pre-existing condition, scoliosis, as a current cause of her pain”)

Martin v. Shell Oil Co., 180 F. Supp. 2d 313, 320 (D. Conn. 2002)

Figueroa v. Boston Scientific Corp., 254 F.Supp. 2d 361, 368 (S.D.N.Y. 2003)(“failure to rule out alternative causes is not determinative of admissibility of evidence but goes to weight, which is for a jury to decide”)

Perkins v. Origin Medsystems, Inc., 299 F. Supp. 2d 45, 57-61 (D. Conn. 2004)

In re Rezulin Prods. Liab. Litig., No. MDL 1348, 00 Civ. 2843(LAK), 2004 WL 2884327, at *3-4 (S.D.N.Y. Dec. 10, 2004) (holding that differential etiology may not be used to prove general causation) (“differential diagnosis does not ‘speak to the issue of general causation. [It] assumes that general causation has been proven for the list of possible causes’ that it rules in and out in coming to a conclusion.”)

In re Ephedra Prods. Liab. Litig., 393 F. Supp. 2d 181, 187 (S.D.N.Y. 2005) (Rakoff, J.)

THIRD CIRCUIT

In re Paoli R.R. Yard PCB Litig., 916 F.2d 829, 862 (3d Cir.1990)

In re Paoli R.R. Yard PCB Litig., 35 F.3d 717, 758 (3d Cir. 1994) (“[D]ifferential diagnosis generally is a technique that has widespread acceptance in the medical community, has been subject to peer review, and does not frequently lead to incorrect results …. )

Wade-Greaux v. Whitehall Labs., Inc., 874 F. Supp. 1441 (D.V. I.), aff’d, 46 F.3d 1120 (3d Cir. 1994) (excluding testimony of expert who failed to rule out alternative causes of plaintiff’s birth defects)

Kannankeril v. Terminex Int’l, Inc., 128 F.3d 802, 807 (3d Cir. 1997)

Heller v. Shaw Indus., Inc., 167 F.3d 146, 154 (3d Cir. 1999) (a medical expert need not “always cite published studies on general causation in order to reliably conclude that a particular object caused a particular illness” so long as there are good grounds, such as differential diagnosis, for the conclusion)

District Courts within 3d Circuit

Wade-Greaux v. Whitehall Labs., Inc., 874 F. Supp. 1441 (D.V. I.), aff’d, 46 F.3d 1120 (3d Cir. 1994) (excluding testimony of expert who failed to rule out alternative causes of plaintiff’s birth defects)

Diaz v. Matthey, Inc., 893 F. Supp. 358, 376-377 (D.N.J. 1995) (excluding testimony and granting summary judgment where expert failed to rule out alternative causes for plaintiff’s asthma)

Rutigliano v. Valley Bus. Forms, 929 F. Supp. 779, 787 (D.N.J. 1996) (excluding expert’s testimony and granting summary judgment where the “record is replete with evidence, including [the expert’s] own admissions, that [plaintiff’s] symptoms could be attributable to medical conditions other than formaldehyde sensitization”)

Reiff v. Convergent Technologies, 957 F. Supp. 573, 582-83 (D.N.J. 1997) (excluding expert’s testimony and granting summary judgment where expert failed to rule out alternative causes of plaintiff’s carpal tunnel syndrome)

O’Brien v. Sofamor, 1999 WL 239414, at *5 (E.D. Pa. Mar. 30, 1999) (excluding expert’s testimony and granting summary judgment where plaintiff “offer[ed] no evidence that [plaintiff’s experts] performed a differential diagnosis, or even considered other potential causes” of plaintiff’s back condition)

Kent v. Howell Elec. Motors, 1999 WL 517106, at * 5 (E.D. Pa. July 20, 1999) (excluding expert testimony and granting summary judgment because expert could “not rule out reasonable alternative theories of what caused the retaining ring to fail”)

Schmerling v. Danek Med., Inc., 1999 WL 712591, at *9 (E.D. Pa. Sept. 10, 1999) (excluding expert’s testimony and granting summary judgment on the grounds that expert’s failure to rule out alternative causes “alone warrants a determination that the expert’s methodology is unreliable”)

Turbe v. Lynch Trucking Inc., 1999 WL 1087026, at *6 (D.V.I. Oct. 7, 1999) (excluding expert’s testimony where expert “expressed awareness of obvious alternative causes” yet “did not investigate any other possible causes”)

In re Paoli R.R. Yard PCB Litig., 2000 WL 274262, at *5 (E.D. Pa. March 1, 2000) (expert’s opinion should be excluded “because she failed to rule out alternative causes” of plaintiff’s injuries)

Magistrini v. One Hour Martinizing Dry Cleaning, 180 F. Supp. 2d 584, 608-610 (D.N.J. 2002) (excluding testimony of expert who sought to testify that dry cleaning fluid caused leukemia, but failed to rule out smoking as an alternative cause) (holding expert witness’s differential methodology unreliable when objection to the opinion points to a plausible alternative cause, and the expert witness offers no explanation for his conclusion that the exposure was a substantial factor in causing plaintiff’s injury)

Yarchak v. Trek Bicycle Corp., 208 F. Supp. 2d 470, 498 (D.N.J. 2002)

Soldo v. Sandoz Pharms. Corp., 244 F.Supp. 2d 434, 554-56, 567 (W.D. Pa. 2003) (excluding experts’ specific causation testimony based on a differential diagnosis because the witnesses “did not demonstrate any valid diagnostic methodology–any ‘sufficient diagnostic technique’–for excluding” other plausible causes as the sole cause of the plaintiff’s injury) (holding that the differential “diagnostic” process is not reliable, and not admissible, unless it reliably rules out reasonable alternative causes or idiopathic causes of the alleged harm); see id. at 524 (differential diagnosis cannot establish general causation)

Perry v. Novartis, 564 F. Supp. 2d 452, 469 (E.D. Penn. 2008)(Dalzell, J.) (“Standing alone, the presence of a known risk factor is not a sufficient basis for ruling out idiopathic origin in a particular case, particularly where most of the cases of the disease have no known cause.”)

FOURTH CIRCUIT

Benedi v. McNeil-P.P.C. Inc., 66 F.3d 1378, 1384 (4th Cir. 1995) (upholding admission of differential diagnosis , reasoning circularly that diagnosing physicians use it)

Cavallo v. Star Enter., 892 F. Supp. 756, 771, (E.D. Va. 1995) (noting that it is not sufficient for an expert to rule out other possible causes if he has no sound evidence that allows him to “rule in” the purported cause), aff’d in relevant part, rev’d in part on other grounds, 100 F.3d 1150 (4th Cir. 1996)

Oglesby v. General Motors Corp., 190 F.3d 244, 250 (4th Cir. 1999) (affirming exclusion of testimony where “as a matter of logic, [the expert] could not eliminate other equally plausible causes” of cracked plastic inlet)

Westberry v. Gislaved Gummi AB, 178 F.3d 257, 262-263 (4th Cir. 1999) (“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”)

Cooper v. Smith & Nephew, Inc., 259 F.3d 194, 202 (4th Cir.2001) (holding that an expert’s opinion based on a differential diagnosis is generally admissible but that there must be adequate evidence that the differential is a cause of the disease)

District Courts within 4th Circuit

Higgins v. Diversey Corp., 998 F. Supp. 598, 603 (D. Md. 1997), aff’d, 135 F.2d 769 (4th Cir. 1998) (excluding expert’s testimony that the accidental inhalation of a bleach caused plaintiff’s injuries, where expert “admit[ted] that he [could] not rule out several other possible causes”)

Driggers v. Sofamor, S.N.C., 44 F. Supp. 2d 760, 765 (M.D.N.C. 1998) (excluding expert’s testimony and granting summary judgment where “expert failed to rule out other possible causes of [plaintiff’s back] pain”)

Aldridge v. Goodyear Tire & Rubber Co., 34 F. Supp. 2d 1010, 1024 (D. Md. 1999), vacated on other grounds, 223 F.3d 263 (4th Cir. 2000) (excluding testimony of plaintiffs’ experts where they “failed to adequately address possible alternative causes of plaintiffs’ illnesses”)

Fitzerald v. Smith & Nephew Richards, Inc., 1999 WL 1489199 (D. Md. Dec. 30, 1999) (excluding expert’s testimony and granting summary judgment where expert “failed to rule out what could have been another cause of [plaintiff’s] condition”)

Shreve v. Sears, Robuck & Co., 166 F. Supp. 2d 378, 397-98 (D. Md. 2001) (excluding testimony where expert failed to rule out other causes of plaintiff’s injury other than an alleged defect in snow thrower)

Smith v. Wyeth-Ayerst Laboratories Co., 278 F.Supp. 2d 684, 692 (W.D.N.C. 2003)(inexplicably rejecting argument that idiopathic causes prevent the use of “differential etiology” method to ascertain specific causation)

Roche v. Lincoln Property Co., 278 F.Supp. 2d 744 (E.D. Va. 2003) (excluding in part expert witness’s testimony that mold caused the plaintiffs’ allergy-like symptoms because he failed “to rule out the Roches’ significant allergies to cats, dust mites, grasses, weeds, and trees as potential causes for the Roches’ symptoms,” which pre-existed moving to the defendant’s apartment)

Doe v. Ortho-Clinical Diagnostics, Inc., 440 F.Supp. 2d 465, 476-78 (M.D.N.C. 2006) (excluding improperly conducted differential diagnosis in thimerosal vaccine autism case)

Hines v. Wyeth, Inc., 2011 WL 2792436, at *3 (S.D.W.V. July 14, 2011) (excluding expert witness who failed properly to rule out alternative causes of breast cancer in hormone therapy case)

FIFTH CIRCUIT

Moore v. Ashland Chem. Inc., 151 F.3d 269, 278-79 (5th Cir. 1998)(en banc), cert. denied, 526 U.S. 1064 (1999)(holding that trial court has discretion to conclude that an expert’s differential diagnosis was insufficiently reliable to be submitted to the jury)

Curtis v. M&S Petroleum, Inc., 174 F.3d 661, 670 (5th Cir. 1999)

Michaels v. Avitech, Inc., 202 F.3d 746, 753 (5th Cir. 2000) (excluding testimony when “plaintiff’s experts wholly fail[ed] to address and rule out the numerous other potential causes” of an aircraft disaster)

Black v Food Lion, Inc, 171 F3d 308 (5th Cir 1999) (expert witness, purporting to use a differential diagnosis, testified that plaintiff’s slip in the supermarket caused fibromyalgia, which is largely idiopathic) (“This analysis amounts to saying that because [the physician] thought she had eliminated other possible causes of fibromyalgia, even though she does not know the real ‘cause,’ it had to be the fall at Food Lion. This is not an exercise in scientific logic but in the fallacy of post-hoc propter-hoc reasoning, which is as unacceptable in science as in law.”)

Johnson v. Arkema, Inc., 685 F.3d 452, 467–68 (5th Cir. 2012) (suggesting that a proper differential diagnosis may be admissible)

District Courts within 5th Circuit

Bennett v. PRC Public Sector, 931 F. Supp. 484, 492 (S.D. Tex. 1996) (excluding testimony of expert who failed to consider and rule out alternative causes of plaintiff’s repetitive motion disorders)

Conger v. Danek Med., Inc., 1998 WL 1041331, at *5-6 (N.D. Tex. Dec. 14, 1998) (excluding expert’s testimony and granting summary judgment when expert “had not attempted to rule out [other potential sources] as causes for [plaintiff’s back] pain”);

Nobles v. Sofamor, 1999 WL 1129661 (S.D. Tex June 30, 1999) (Rosenthal, J.)

Leigh v. Danek Med., Inc., 1998 WL 1041329, at *4-5 (N.D. Tex. Dec. 14, 1998) (excluding expert’s testimony and granting summary judgment where expert failed to rule out alternative causes of plaintiff’s back pain)

In re Propulsid Products Liability Litigation, 261 F. Supp. 2d 603, 618 (E.D. La. 2003)(“They also cannot rule out other explanations for the measurements that form the predicate of the QTc, the heart rate, or heart rate variability)

Cano v. Everest Minerals Corp., 362 F. Supp. 2d 814, 844-46 (W.D. Tex. 2005) (addressing specific causation in context of known carcinogen (radiation), and holding that expert witness’s methodology of concluding that any cause that could have been a cause was in fact a cause and a substantial factor was invalid)

Ridgeway v. Pfizer Inc., No. 2:09-cv-02794, 2010 WL 1729187, *4 (E.D.La. April 27, 2010) (using “differential diagnosis,” or res ipsa loquitur, the proponent bears the burden of “excluding  reasonable explanations for the accident other than defendant’s negligence”)

SIXTH CIRCUIT

Glaser v. Thompson Med. Co., 32 F.3d 969, 978 (6th Cir. 1994) (differential diagnosis defined as “standard diagnostic tool used by medical professionals to diagnose the most likely cause or causes of illness, injury and disease”)

Hardyman v. Norfolk & W. Ry. Co., 243 F.3d 255, 260 (6th Cir.2001) (“Differential diagnosis … is a standard scientific technique of identifying the cause of a medical problem”)

Downs v. Perstorp Components, Inc., 26 F. Appx. 472, 476–77 (6th Cir. 2002) (holding that exclusion of expert’s opinion was appropriate when arrived at by a “methodology primarily [that] involved reasoning backwards from Downs’ condition and, through a process of elimination, concluding that [defendant’s product] must have caused it”)

Best v. Lowe’s Home Centers, Inc., 563 F. 3d 171, 178-80 (6th Cir. 2009)

Gass v. Marriott Hotel Servs., 558 F.3d 419, 426 (6th Cir. 2009) (“the ability to diagnose medical conditions is not remotely the same as the ability to deduce … in a scientifically reliable manner the causes of those medical conditions”)(internal citations omitted)

Tamraz v. BOC Group Inc., No. 1:04-CV-18948, 2008 WL 2796726 (N.D. Ohio July 18, 2008) (denying Rule 702 challenge to treating physician’s causation opinion), rev’d sub nom., Tamraz v. Lincoln Elec. Co., 620 F.3d 665, 673 (6th Cir. 2010) (carefully reviewing record of trial testimony of plaintiffs’ treating physician; reversing judgment for plaintiff based in substantial part upon treating physician’s speculative causal assessment created by plaintiffs’ counsel; “Getting the diagnosis right matters greatly to a treating physician, as a bungled diagnosis can lead to unnecessary procedures at best and death at worst. But with etiology, the same physician may often follow a precautionary principle: If a particular factor might cause a disease, and the factor is readily avoidable, why not advise the patient to avoid it? Such advice—telling a welder, say, to use a respirator—can do little harm, and might do a lot of good. This low threshold for making a decision serves well in the clinic but not in the courtroom, where decision requires not just an educated hunch but at least a preponderance of the evidence.”) (internal citations omitted), cert. denied, ___ U.S. ___ , 131 S. Ct. 2454, 2011 WL 863879 (2011)

Thomas v. Novartis Pharm. Corp., 443 Fed. App’x 58, 61-62 (6th Cir. 2011) (excluding expert witnesses in cases involving osteonecrosis of the jaw, allegedly caused by bisphosphonate medication, for failing to conduct proper differential analysis; emphasizing “the importance of correctly determining the cause of the osteonecrosis … does nothing to establish that [the doctor] can in fact, reliably determine the cause of a patient’s [osteonecrosis]”)

District Courts within 6th Circuit

Nelson v. Tennessee Gas Pipeline Co., 1998 WL 1297690, at *6 (W.D. Tenn. Aug. 1, 1998) (excluding testimony of expert who “failed to engage in adequate techniques to rule out alternative causes and offers no good explanation as to why his opinion is nevertheless reliable in light of other potential causes of the alleged injuries”)

Downs v. Perstorp Components, 126 F. Supp. 2d 1090, 1127 (E.D. Tenn. 1999) (excluding expert testimony as to whether exposure to chemicals caused plaintiff’s injuries where expert failed to rule out alternative causes)

Huffman v. SmithKline Beecham Clinical Lab., Inc., 111 F. Supp. 2d 921, 930 (N.D. Ohio 2000)

Asad v. Continental Airlines, Inc., 314 F. Supp. 2d 726 (N.D. Ohio 2004)

SEVENTH CIRCUIT

O’Connor v. Commonwealth Edison, 13 F.3d 1090, 1106 (7th Cir. 1994) (holding that physician’s testimony that  cataracts were caused by radiation exposure based upon visual examination of the plaintiff’s was not reliably supported by clinical examination), cert. denied, 114 S.Ct. 2711 (1994).

Ervin v. Johnson & Johnson, Inc., 492 F.3d 901, 904 (7th Cir.2007)(noting that “[a] differential diagnosis satisfies a Daubert analysis if the expert uses reliable methods”) (excluding differential etiological testimony that was based upon ruling a particular potential specific cause based on temporal proximity)

District Courts within 7th Circuit

Schmaltz v. Norfolk & Western Ry., 878 F.Supp. 1122 (N.D. Ill. 1995)

Lennon v. Norfolk & Western Ry., 123 F.Supp.2d 1143, 1153 (N.D.Ind. 2000) (excluding neurologist’s unreliable causal attribution of multiple sclerosis to fall)

Eve v. Sandoz Pharm. Corp., No. IP 98-1429, 2001 U.S. Dist. LEXIS 4531 (S.D. Ind. 2001)

Caraker v. Sandoz Pharms., 188 F. Supp. 2d 1026, 1030 (S.D. Ill. 2001) (when a differential diagnosis is employed “in the practice of science (as opposed to its use by treating physicians in the practice of medicine out of necessity) it must reliably ‘rule in’ a potential cause”)

Bickel v. Pfizer, Inc., 431 F.Supp. 2d 918, 923 (N.D. Ind. 2006) (“the Plaintiff cannot rely on [differential] diagnosis to establish general causation”)

EIGHTH CIRCUIT

National Bank of Commerce v. Assoc. Milk Producers, 22 F. Supp. 2d 942, 963 (E.D. Ark. 1998), aff’d, 191 F.3d 858 (8th Cir.1999) (excluding testimony and granting summary judgment where expert did “not successfully rule out other possible alternative causes” for cancer)

Turner v. Iowa Fire Equip. Co., 229 F.3d 1202, 1208-09 (8th Cir. 2000) (“[A] medical opinion about causation, based upon a proper differential diagnosis, is sufficiently reliable to satisfy Daubert.”)(“If a properly qualified medical expert performs a reliable differential diagnosis through which, to a reasonable degree of medical certainty, all other possible causes of the victims’ condition can be eliminated, leaving only the toxic substance as the cause, a causation opinion based on that differential diagnosis should be admitted.”)

Bonner v. ISP Technologies, Inc., 259 F.3d 924, 1208 (8th Cir. 2001)

Glastetter v. Novartis Pharms. Corp., 252 F.3d 986, 989 (8th Cir. 2001) (per curiam) (“[T]he district court excluded the differential diagnoses performed by Glastetter’s expert physicians because they lacked a proper basis for ‘ruling in’ Parlodel as a potential cause of [an intracerebral hemorrhage] in the first place. . . . We agree with the district court’s conclusion.”)

Jazairi v. Royal Oaks Apts., 217 Fed. Appx. 895 (8th Cir. 2007) (excluding differential etiological testimony that was based upon ruling a particular potential specific cause based on temporal proximity)

Bland v. Verizon Wireless, L.L.C., 538 F.3d 893, 897 (8th Cir. 2008) (affirming exclusion of treating physician’s differential diagnosis)

District Courts within 8th Circuit

Stover v. Eagle Products, 1996 WL 172972, at *11 (D. Kan. Mar. 19, 1996) (excluding testimony of expert who “[did] not explain in any meaningful detail how he [was] able to exclude the numerous multiple alternative causes” of injury to plaintiff’s dogs) (excluding expert testimony for failing to rule out alternative causes)

Bruzer v. Danek Med., Inc., 1999 WL 613329, at *8 (D. Minn. Mar. 8, 1999) (excluding expert’s testimony and granting summary judgment where expert did “not attempt to rule out any alternative potential causes for [plaintiff’s] continuing and increasing [back] pain”) (excluding expert testimony for failing to rule out alternative causes)

Thurman v. Missouri Gas Energy, 107 F. Supp. 2d 1046, 1058 (W.D. Mo. 2000) (expert’s opinion “that the pipeline failed because of corrosion” was excluded and summary judgment granted where expert reached the conclusion “without eliminating other causes”) (excluding expert testimony for failing to rule out alternative causes)

Jisa Farms, Inc. v. Farmland Indus., No. 4:99CV3294, 2001 U.S. Dist. LEXIS 26084 (D. Neb. 2001) (excluding expert testimony for failing to rule out alternative causes)

In re Viagra Prod. Liab. Litig., 658 F. Supp. 2d 950, 957 (D. Minn. 2009)

NINTH CIRCUIT

Kennedy v. Collagen Corp., 161 F.3d 1226, 1228-30 (9th Cir. 1998)

Clausen v. M/V NEW CARISSA, 339 F.3d 1049, 1057 (9th Cir. 2003)

Messick v. Novartis Pharms., ___ F.3d. ___, 2014 WL 1328182 (9th Cir. 2014)

District Courts within 9th Circuit

Hall v. Baxter Healthcare Corp., 947 F.Supp. 1387, 1413 (D.Ore. 1996) (explaining that differential diagnosis assumes general causation has been established) (“differential diagnosis does not by itself prove the cause, even for the particular patient. Nor can the technique speak to the issue of general causation.”)

TENTH CIRCUIT

Hollander v. Sandoz Pharms. Corp., 289 F.3d 1193, 1211 (10th Cir. 2002) (stating that “experts would need to present reliable evidence that the drug can cause strokes” before differential diagnosis could be admissible)

Goebel v. Denver & Rio Grande W. RR., 346 F.3d 987, 999 (10th Cir. 2003)

Tingey v. Radionics, 193 Fed. Appx. 747, 763 (10th Cir. 2006)

District Courts within 10th Circuit

Stover v. Eagle Products, 1996 WL 172972, at *11 (D. Kan. Mar. 19, 1996) (excluding testimony of expert who “[did] not explain in any meaningful detail how he [was] able to exclude the numerous multiple alternative causes” of injury to plaintiff’s dogs)

In re Breast Implant Lit., 11 F. Supp. 2d 1217, 1230, 1234 (D. Colo. 1998) (excluding expert testimony where expert failed to “explain what alternative causes he considered, or how he ruled out other possible causes” of plaintiffs’ auto- immune disease) (“Differential diagnosis may be utilized by a clinician to determine what recognized disease or symptom the patient has, but it is incapable of determining whether exposure to a substance caused disease in the legal sense.”)

ELEVENTH CIRCUIT

McClain v. Metabolife Int’l, Inc., 401 F.3d 1233, 1252-53 (11th Cir.2005) (detailing a reliable differential diagnostic process)(“A valid differential diagnosis, however, only satisfies a Daubert analysis if the expert can show the general toxicity of the drug by reliable methods.”)

Rink v. Cheminova, Inc., 400 F.3d 1286, 1295 (11th Cir. 2005) (holding that a differential diagnosis alone does not support a finding of causation where no expert testimony from a treating physician or toxicologist is presented, or any toxicological evidence produced; specifically rejecting the Westberry)  (“[I]n the context of summary judgment . . . differential diagnosis evidence by itself does not suffice for proof of causation.”)

Guinn v. AstraZeneca Pharms. LP, 602 F.3d 1245 (11th Cir. 2010), aff’g 598 F. Supp. 2d 1239, 1243 (M.D. Fla. 2009) (excluding expert witness’s specific causation opinion for failing “to articulate any scientific methodology for assessing whether, and to what extent, Seroquel contributed to Guinn’s weight gain and diabetes”)

Hendrix v. Evenflo Co., 609 F.3d 1183, 1194-95 (11th Cir. 2010), aff’g, 255 F.R.D. 568, 596 (N.D. Florida, 2009)(differential etiology not diagnosis)

Kilpatrick v. Breg, Inc., 613 F.3d 1329, 1342 (11th Cir. 2010) (noting that differential diagnosis “assumes the existence of general causation”)

District Courts within 11th Circuit

Coleman v. Danek Med., Inc., 43 F. Supp. 2d 637, 650 n. 23 (S.D. Miss. 1999) (stating that “in reaching his conclusion that these plaintiffs were injured by Danek’s product, Dr. Aldreti did not rule out other causes of their alleged injuries. Thus, his conclusion that their injuries were caused by Danek’s product is based on pure speculation – and is not a valid differential diagnosis.”)

Siharath v. Sandoz Pharms. Corp., 131 F. Supp. 2d 1347, 1356-71 (N.D. Ga. 2001) (holding that differential diagnosis cannot rule in a general causal factor, and noting in Parlodel case that “[e]xperts must do something more than just ‘rule out’ other possible causes. They must explain how they were able to ‘rule in’ the product in question”), aff’d sub nom., Rider v. Sandoz Pharm. Corp., 295 F.3d 1194 (11th Cir. 2002).

D.C. CIRCUIT

Ambrosini v. Labarraque, 101 F.3d 129, 140 (D.C.Cir.1996) (describing the appropriate use of differential diagnosis to prove specific causation)

Meister v. Med. Eng’g Corp., 267 F.3d 1123, 1129, 347 U.S. App. D.C. 361 (D.C. Cir. 2001)(“whatever factors remain after other alternative causes have been eliminated [must be] at least capable of causing the disease in question”)

STATE COURT CASES

ALASKA

John’s Heating Service v. Lamb, 46 P.3d 1024 (Alaska 2002) (“[a] differential diagnosis that fails to take serious account of other potential causes may be so lacking that it cannot provide a reliable basis for an opinion on causation,” but not in this case involving carbon monoxide poisoning)

ARIZONA

Lofgren v. Motorola, No. CV 93-05521, 1998 WL 299925, at *24 (Ariz. Super. Ct. June 1, 1998) (differential diagnosis as a method of determining the cause of disease has been “unequivocally rejected by the scientific community”)

IOWA

Ranes v. Adams Labs., Inc., 778 N.W.2d 677, 690 (Iowa 2010)(general causation for each differential should be established by adequate evidence)

KANSAS

Kuhn v. Sandoz Pharms., 14 P.3d 1170, 1173-78 (Kan. 2000) (Frye test not applicable to “pure opinion” testimony such as differential diagnosis)

LOUISIANA

Keener v. Mid-Continent Cas., 817 So. 2d 347 (La. Ct. App. 5th Cir. 2002), writ denied, 825 So. 2d 1175 (La. 2002)

MINNESOTA

Zandi v. Wyeth, 2009 Minn. App. Unpub. LEXIS 785, at *17-18 (Minn. Ct. App. July 21, 2009), petition denied, 2009 Minn. LEXIS 648 (Minn. Sept. 29, 2009)

NEW JERSEY

Creanga v. Jardal, 185 N.J. 345, 886 A.2d 633 (2005) (holding that properly conducted differential diagnosis was admissible; reversing exclusion of physician testimony in case)

OHIO

Terry v. Ottawa Cty. Bd. of Mental Retardation & Developmental Delay, 658, 847 N.E.2d 1246 (Ohio Ct. App. 2006) (“We agree with the trial court: Dr. Bernstein did not conduct a scientifically valid differential diagnosis, because his method relied primarily upon temporal relationships and because he did not rule out other possible causes. He was properly barred from testifying to specific causation.”)

TEXAS

Mitchell Energy Corp. v. Bartlett, 958 S.W.2d 430, 448 (Tex. App.–Fort Worth 1997, pet. denied) (“Dr. Basset’s failure to rule out other causes of the presence of hydrogen sulfide in appellees’ water renders his opinion ‘little more than speculation.’”)

Weiss v. Mechanical Associated Services, Inc., 989 S.W.2d 120, 126 (Tex. App.– San Antonio 1999, pet. denied) (affirming summary judgment for the defendants in a case involving injuries allegedly caused by exposure to a chemical, because “none of Weiss’ experts were able to rule out other potential causes of Weiss’ illness with reasonable certainty”)

Williams v. NGF, Inc., 994 S.W.2d 255, 257 (Tex. App.–Texarkana 1999, no pet. h.) (affirming summary judgment for defendant because plaintiffs “failed to produce evidence which excluded the possibility that . . . other flowers or chemical agents used on them were the cause of her injuries”)

Austin v. Kerr-McGee Refining Corp., 25 S.W.3d 280, 293 (Tex. App.-Texarkana 2000, no pet.) (affirming summary judgment for defendants; trial court properly excluded plaintiffs’ scientific evidence because, among other reasons, plaintiffs “failed to exclude other plausible causes with reasonable certainty”)

Martinez v. City of San Antonio, 40 S.W.3d 587, 595 (Tex. App.–San Antonio 2001, no pet.) (“The opinions of Matson and Baynes, when offered to prove Alamodome site lead caused appellants’ injuries, constitute no evidence because Matson, in arriving at his lead calculation, failed to rule out alternative sources of the lead contamination.”)

Neal v. Dow Agrosciences L.L.C., 74 S.W.3d 468, 473 n. 3 (Tex. App. – Dallas 2002, no pet.)(describing “differential diagnosis” as a patient-specific process of elimination) (citing Minnesota Min. And Mfg. Co. v. Atterbury, 978 S.W.2d 183, 194 n. 9 (Tex. App. – Texarkana 1998, pet. denied)

Coastal Tankships, USA, Inc. v. Anderson, 87 S.W.3d 591, at 609-10 (2002)(“In the toxic-tort context, a plaintiff must establish general causation for a differential diagnosis to be relevant to show specific causation.”)

UTAH

Alder v. Bayer Corp., AGFA Div., 61 P.3d 1068, 1084–85 (Utah 2002)

VERMONT

Blanchard v. Goodyear Tire & Rubber Co.,  2011 Vt. 85, 30 A.3d 1271 (2011)(holding that plaintiff’s claim that his NHL was caused by benzene was not reliably supported by differential diagnosis when a large percentage of NHL cases have no known cause)

WYOMING

Easum v. Miller, 92 P.3d 794, 802 (Wyo. 2004) (“Most circuits have held that a reliable differential diagnosis satisfies Daubert and provides a valid foundation for admitting an expert opinion. The circuits reason that a differential diagnosis is a tested methodology, has been subjected to peer review/publication, does not frequently lead to incorrect results, and is generally accepted in the medical community.”) (quoting Turner v. Iowa Fire Equip. Co., 229 F.3d 1202, 1208 (8th Cir. 2000)

COMMENTATORS

Conley & Garver,  “William C. Keady and the Law of Scientific Evidence,” 68 Miss. L.J. 39, 51 (1998) (differential diagnosis is “a mixture of science and art, far too complicated for its accuracy to be assessed quantitatively or for a meaningful error rate to be calculated”)

Wendy Michelle Ertmer, “Just What the Doctor Ordered: The Admissibility of Differential Diagnosis in Pharmaceutical Product Litigation,” 56 Vand. L. Rev. 1227 (2003)

Joe G. Hollingsworth & Eric G. Lasker, “The Case Against Differential Diagnosis: Daubert, Medical Causation Testimony, and the Scientific Method,” 37 J. Health Law 85, 98 (2004)

Edward J. Imwinkelried,, “The Admissibility and Legal Sufficiency of Testimony about Differential Diagnosis (Etiology): Of Under‑ and Over‑Estimations,” 56 Baylor L. Rev. 391, 406 (2004)

Michael B. Kent Jr., “Daubert, Doctors and Differential Diagnosis: Treating Medical Causation Testimony as Evidence,” 66 Def. Couns. J. 525 (1999)

Joseph Sanders, “Applying Daubert Inconsistently? Proof of Individual Causation in Toxic Tort and Forensic Cases,” 75 Brooklyn L. Rev. 1367 (2010)

Joseph Sanders & Julie Machal-Fulks, “The Admissibility of Differential Diagnosis Testimony to Prove Causation in Toxic Tort Cases: The Interplay of Adjective and Substantive Law,” 64 Law & Contemp. Prob. 107 (2001)

Ian S. Spechler, “Physicians at the Gates of Daubert: A Look at the Admissibility of Differential Diagnosis Testimony to Show External Causation in Toxic Tort Litigation,” 26 Rev. Litig. 739 (2007)

Teratology Society, Public Affairs Committee, “Teratology Society Public Affairs Committee Position Paper Causation in Teratology-Related Litigation,” 73 Birth Defects Research (Part A) 421, 423 (2005) (“7. Biologic plausibility is an essential element in establishing causation. *** The consideration of alternative explanations is sometimes misused by expert witnesses to mean that failure to find an alternative explanation for an outcome is proof that the exposure at issue must have caused the outcome. A conclusion that an exposure caused an outcome is, however, based on positive evidence rather than on lack of an alternative explanation.”)