Medical Negligence

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Applied forensic epidemiology, part 1: medical negligence

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Methods Development MD Freeman *, PJ Cahn , FA Franklin

Abstract Conclusion demiology, is generally described as Introduction Causation in cases of alleged medi- concerning the intersection of epide- The evaluation of the causal relation- cal malpractice is commonly disput- ship between an alleged act of medical provides a systematic approach to the negligence and an adverse health out- causation is not a viable alternative miology and law. More specifically, FE come is an essential element of a med- (i.e.ed. Inthe cases diagnosis in which can directhave multiple specific causation in civil and criminal mat- ical malpractice legal action. In such causes), the indirect evaluation of tersinvestigation3–5. In a clinical of general setting, and the specific evalu- an action, the question of causation is ation of causation is invariably per- also known as the “but-for” question; described in this article provides a formed by clinicians (e.g. a patient’s i.e. but for the negligent act, would the reliablespecific methodologic causation via framework the methods for ischaemic stroke was caused by his plaintiff still have suffered the adverse uncontrolled high blood pressure), outcome at the same point in time? of causation suitable for presenta- and as such it is rare that a causal de- Forensic epidemiology provides a sys- tionthe quantificationin a court of law. of the probability termination is ever revisited or chal- tematic approach to the investigation lenged. In the legal setting, however, of causation, with conclusions suitable Introduction causation is routinely disputed. FE for presentation in a medicolegal set- Causation plays a pivotal role in the - ting. Such an evaluation relies on the evaluation of legal actions involving fers from the clinical evaluation of following steps: (1) the application an allegation of medical negligence. causationevaluation in of that specific the former causation focuses dif Once it is established that an action on an analysis of the risk of injury or conclusion that an investigated negli- (either commission or omission) has disease from the investigated hazard gentof the action Hill criteriawas a plausible to first cause arrive of at an a occurred and that an adverse health versus the competing risk of the inju- adverse outcome; (2) an assessment outcome has followed that action, ry or disease absent in the exposure of the temporo-spatial relationship there are two questions that must to the hazard, whereas the latter fo- between the negligent action and the be answered in order for the claim to cuses more on the differential diag- advance legally. First, the action (al- nosis and patient history6. - leged ‘hazard’) must be plausibly re- In many instances, there is no need ityfirst of indication causation of via the an adverse estimate outcome of the lated to the adverse outcome. In legal for an FE evaluation of causation in riskand (3)of quantificationinjury associated of the with probabil negli- settings, this relationship is often re- a legal setting; e.g. it is unlikely that gent action versus the risk of known ferred to as general causation1. Next, there will be a dispute over cause of contemporaneous alternative causes it must be demonstrated, on a more death when the hazard is a gunshot likely than not basis (>50% probabil- wound to the head. This form of spe- of a three-part series on applied fo- ity), that in the absence of exposure direct, since there rensicof the epidemiology, adverse outcome. we demonstrate In this first to the hazard, the outcome would not - forensic epidemiology methods with a have occurred in the individual1,2. In tweencific causation the diagnosis is of the condition description of the investigation of the a tort action for personal injury, this andis a the high cause degree of the of specificitycondition; bei.e. probability of causation in three cases is known as the ‘but-for’ question; the death was caused by a gunshot of serious neurologic injury following but for the hazard, would the plaintiff wound, and such wounds are only an alleged act of medical negligence. still have suffered the adverse outcome at the same point in time? The causation is only practical when the process of answering this question is diagnosiscaused by and gunshots. the cause Direct are specificessen- * Corresponding author declared in the article. Conflict of interests: Email: [email protected] tially inseparable. 1 Oregon Health & Science University School causation. With this information, a In circumstances in which medical of Medicine, Departments of Public Health & referred to as specific or individual- negligence is alleged as a cause of an Preventive Medicine and Psychiatry, Portland, mination of negligence and damages. adverse outcome, it is rare that there Oregon, USA 2 Forensic Research & Analysis, Portland, factThe finder practice can makeof forensic a further epidemiol deter- are not at least several alternative ex- Oregon, USA ogy (FE), also referred to as legal epi- planations for the outcome, including

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Freeman MD, Cahn PJ, Franklin FA. Competing interests: none declared. interests: Competing the final manuscript. preparation, read and approved and design, manuscript conception to All authors contributed rules of disclosure. ethical Ethics (AME) for Medical the Association All authors abide by For citation purposes: Applied forensic epidemiology, part 1: medical negligence. OA Epidemiology 2014 Jan 18;2(1):2. Page 2 of 11

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that it was a natural consequence of likelihood that the conduct falls with- predictive characteristics. This le- the disease or injury necessitating in the scope of liability. As a result, whether the defendant’s conduct is a In such cases, there will be differ- proximate cause of harm becomes a inquirygally accepted process approach used in toFE specificknown ingthe opinions medical careon causation, in the first typically place. function of risk probability. The court ascausation differential reflects aetiology the counterfactual11. Unlike the provided by clinicians on either side must ask what risks the defendant differential diagnosis approach of of the legal dispute. The differences should have anticipated at the time medical causation, differential ae- of opinion often stem from disputes he acted and compare those risks tiology generally does not rely on a over the magnitude of the competing with the injury that actually occurred. single case and frequently offers a causes of the outcome, and described The ‘risk rule’ approach adopted by more robust examination of causal (either quantitatively or qualitative- the law provides an analytical basis risk. Although inherently designed to ly) in terms of competing risks. This for consistent decision-making. address general causation, the juris- The RR is an epidemiologic metric prudential view of epidemiological is indirect, in that there is nothing used to quantify general causation or studies is that they are strong evi- form of specific causation evaluation the association between an exposure 9. to only one possible cause. Risk is and the risk probability of disease or aabout population-based the diagnosis thatparameter, is specific in- injury (i.e. harm)8. Given that proxi- Thedence Hill of specificcriteria: causation indirect tended to describe the probability of mate cause and general causation are estimation of the probability of a particular outcome, and opinions conceptually linked by the probability specific cause regarding risk are ultimately based of risk, then, inherently, epidemiology on epidemiologic concepts and data. becomes the most suitable tool to as- via adaptation of the Hill criteria to Thus, the purpose of FE in medical sess proximate cause and, ultimately, theSpecific circumstances causation isof assessed an individual in FE negligence actions is to provide an inform the legal question of liability. case3,12. The Hill criteria, named for evidence-based foundation for opin- If there is no direct evidence of causa- a 1965 publication by Sir Austin ions of comparative or relative risk tion for either an investigated or al- Bradford-Hill, consist of nine criteria (RR) intended to indirectly address ternative cause then a general causal or ‘viewpoints’ by which population- - based determinations of causation causation. tion determination1,9. Epidemiological can be made when there is substan- the ultimate question of specific inference can inform a specific causa- tial epidemiologic evidence linking a three-part series on the applications sation by providing the probability or disease or injury with an exposure13. of InFE the in present civil and article, criminal the first courts, of a likelihoodevidence of that a RR the informs exposure specific caused cau The nine criteria, and how they can we describe the methods and data harm in a randomly selected case is at sources used in the investigation least the proportion described by the are as follows: attributable fraction (AF) and indicat- 1.apply Strength to a specific of association: causation Strengthanalysis, cases of alleged medical negligence ed by effect magnitude of the RR. To- of association is generally con- andof general illustrate and the specific methods causation with the in gether, the RR and AF inform the read- sidered to be the most important analyses of three actual cases. er of the minimum number of excess determinant of causation. Most cases among the exposed population simply stated, a strong associa- Causation and the law that can be attributed to the exposure tion is more likely to indicate a In the law, a legal element of negli- and not the total or maximum num- causal relationship than is a weak gence is whether or not the plaintiff’s ber of cases that can be attributed to association. Strength of associa- exposure to the defendant’s conduct the exposure10. proximately caused the plaintiff’s in- A study presenting a RR supports (the frequency of the condition juries7. Negligence law operationalis- amongtion is typicallythe exposed quantified versus byunex RR- es the proximate cause element as a actual cause), particularly when ac- posed populations), but can also showing of harmful conduct that falls a finding of specific causation (i.e. be measured in general causa- within the scope of liability (i.e. risk, that supports causation and rules tion by the percentage decrease used here qualitatively). Whether the outcompanied independent by case-specific alternate causes evidence as of an illness or injury in society declared in the article. Conflict of interests: harmful conduct is within the scope more probable. The extent to which a if the injury cause were to be of risk is gauged by the concept of eliminated. foreseeability. As the probability of the increased risk to an individual risk increases, the more foreseeable dependsgroup-based on the study individual’s outcome similar reflects- strength of association is evalu- that harm becomes and, in turn, a ity to the subjects in the study pop- ated In by specificcomparing causation, the risk of thein- greater foreseeability enhances the ulation, with regard to substantial jury or disease associated with

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exposure with the hazard to the a. Temporal plausibility: The out- increase in injury response is risk of the same injury or disease come may not occur before - occurring at the same point in time or after the effect range of the tion in an individual case. - hazard. For example, some food- 6. Biologicalstrong evidence plausibility: of specific The causa ob- dividual, but absent the hazard. borne illnesses (i.e. campylo- served association can be plausi- as the exposure in the specific in bacteriosis) only manifest after causation is closely associated a matter of hours or days of in- principles. Hill put little stock in withStrength the ofproximity, association either in specifictempo- cubation, and thus an individu- plausibility,bly explained asserting by known that scientific it was ral or spatial, between the expo- al who falls ill within minutes of a criterion ‘that I am convinced sure and the outcome. Absent con- eating undercooked chicken at we cannot demand’, as detailed founding, the closer the exposure a restaurant in which C. jejuni is to a plausibly related outcome in is found on the food prepara- injury or disease mechanism may time or space, the more likely it is tion surfaces was not plausibly lagscientific behind evidence observational describing evidence an that there is a causal association. made ill by the consumption of a consistently observed causal 2. Consistency: The repetitive ob- of the chicken, despite other association8. Although Hill only servation of a causal relation- collateral evidence suggest- referred to this criterion as plau- ship in different circumstances ing causality. Alternatively, the sibility, for the purposes of this strengthens the causal inference. otherwise unexplained death discussion, we are referring to it Evidence of consistency can come of a patient occurring 3 days as biological plausibility in order from multiple studies of varied after receiving an injection of a to distinguish this criterion from short-acting opiate (i.e. hydro- general plausibility, as discussed consistency may also come from morphone) is not plausibly re- later in this article. As a practical evidencepopulations. gathered In specific in case causation, clusters lated to the injection. matter, biological plausibility is or outbreaks. b. Temporal latency: For an out- typically easily established for the 3. Specificity: In general causation, come that occurs within the majority of causal assessments. A this refers to the degree to which hazard period (HP), the quanti- common error with plausibility an exposure is associated with assessments is to transpose low a particular outcome or popula- - pre-event probability of injury cationfication of of disease the latency or injury between can and implausibility of injury7. is a relatively rare attribute, as bethe importantexposure andin assessingthe first indi the As an example, laceration of mosttion. Specificityexposures can of acause high various degree causal association. As an exam- the iliac artery during a total hip diseases or injuries (e.g. cigarette ple, a death in a hospital patient replacement procedure is very smoking does not only cause lung that occurs within 20 min of an rare15. The rarity of such a com- . cancer). The concept of reverse injection of hydromorphone is plication does not make it implau- much more likely to be asso- sible that the injury would occur an outcome is associated with ciated with the injection than in a surgery that requires the anspecificity, exposure, the is degreeone that to may which be one that occurs 3 h later, largely use of sharp instruments in the - because the cumulative risk of vicinity of the iliac artery. In the ations as well. For example, meso- competing causes of the death context of causation, plausibility theliomaimportant is in only specific associated causal evalu with is directly related to the latency and implausibility should not be asbestos exposure, and therefore period between the exposure considered as complements with evidence of the disease is equal to no middle ground (as is the case evidence of the cause14. of the adverse outcome. with possibility [a probability of 4. Temporality: Hill only described 5. Biologicalto the hazard gradient: and The the firstoutcome sign >0] and impossibility [probability sequence with regard to tempo- increases monotonically with in- of 0]). A causal relationship that rality; that the ‘horse not come be- creasing dose of exposure (also may not be generally considered fore the cart’. Temporal sequence known as ‘dose–response’). This biologically plausible (reason- Conflict of interests: declared in the article Conflict of interests:

is the sine qua non criterion has most relevance in able) is not necessarily consid- . causation that must be present ered implausible (unreasonable), in order to proceed withof specificfurther adverse drug reactions and expo- as the mechanism by which the analysis. Two other parameters surespecific to toxiccausation substances. assessments Multiple of relationship exists may simply be of temporality are also important exposures to increasing levels of a unknown at the present time. This drug or other harmful substance is not to say, however, that when causation: that result in a corresponding implausibility is well established to consider in evaluating specific Licensee OA Publishing London 2014. Creative Commons Attribution License (CC-BY)

Freeman MD, Cahn PJ, Franklin FA. Competing interests: none declared interests: Competing the final manuscript. preparation, read and approved and design, manuscript conception to All authors contributed rules of disclosure. ethical Ethics (AME) for Medical the Association All authors abide by For citation purposes: Applied forensic epidemiology, part 1: medical negligence. OA Epidemiology 2014 Jan 18;2(1):2. Page 4 of 11

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that it should or can be ignored. (where there will not be a re-expo- coherence, analogy and consist- Implausibility is present when a sure), but in the context of medical ency. There is no set number of well-established biological prin- negligence, it is ideal for evaluating criteria that must be met to sat- ciple must be violated in order to causation between repeated expo- isfy a conclusion of general plau- proceed with a causal assessment. sures and adverse events. sibility; this is a judgement to be An example of an implausible re- Steps to the assessment and quan- made by the investigator1. lationship would be the new onset tification of the probability of specific (2) The risk of injury associated of a Parkinson’s disease-related causation when medical negligence with the hazard (hazard risk tremor within hours of a biopsy has been alleged as the cause of an ad- performed under local anaesthet- verse outcome epidemiologic data or study. This ic. To attribute the tremor to the (1) A generally plausible relation- evidence[HR]) is quantified may come via from available previ- biopsy simply because it followed ship between the alleged act of ously published well-designed it closely in time, and at the same negligence and the adverse out- epidemiologic study, or it may time ignore the implausibility of come from analysis of informa- the relationship, is to commit the present. This is accomplished in tion from existing data. There are post hoc ergo propter hoc fallacy. onecome or must both be of first two deemed ways: (i) to the be some situations in which there is 7. Coherence: A causal conclusion relationship is widely accepted no need to quantify the risk of in- should not fundamentally contra- as generally plausible, a fact jury from a hazard because there dict present substantive knowl- that is typically established via is no reasonable dispute that the edge—it should ‘make sense’ giv- review of previously published injury is certain when the hazard en current knowledge. biomedical literature or (ii) via is present. An example would be 8. Experiment: In some cases, application of the seven Hill cri- death following the alleged fail- there may be evidence from ran- teria that address the question ure to provide treatment for a domised experiments on animals of general causation. In order of cardiac arrest. Common sense, or humans. Absence of experi- decreasing utility and/or avail- as well as cardiac physiology and mental evidence of an injury or ability of evidence, these crite- medical experience, tells us that disease mechanism should not be ria are as follows: coherence, it is nearly certain (>95% prob- confused with evidence against an ability) that an untreated cardiac investigated causal relationship. biologic plausibility, experiment arrest will result in death21. The 9. Analogy: An analogous exposure andanalogy, biologic consistency, gradient). specificity, General causation question in such a case and outcome may be translatable plausibility in the context of a might relate to the strength of a to the circumstances of a previous- competing cause of death (e.g. ly unexplored causal investigation. refers to what is both possible sepsis) for which it is alleged An additional causal criterion that was (i.e.specific not established causation evaluationas impos- that the injury would have oc- not mentioned by Hill but which has sible) and reasonable. It is not curred regardless of the expo- been included by subsequent authors the same as Hill’s use of plausi- sure to the hazard. - bility, (3) The temporal proximity between sation when an exposure is repeated to the biologic mechanism by the hazard and the outcome overas an time important is cessation/dechallenge–re feature of specific cau- which whichthe hazard was acted more in specific order challenge16–20. The concept of dechal- to cause the outcome (and thus - lenge–rechallenge is straightforward: is sometimes referred to as bio- icallyis quantified gleaned (thefrom HP)a careful via there- does the adverse effect improve or logic plausibility). A hypothetical viewevidence of the specific medical to therecord, case, and/ typ resolve in a temporally appropriate example of a generally plausible or interview of fact witnesses. manner when the exposure is stopped relationship that cannot meet (4) The base rate at which the injury or the degree of exposure is lessened Hill’s plausibility criterion would or condition would be expected (dechallenge) and does it return in a be an outbreak of gastroenteritis to occur during the HP absent temporally appropriate manner when among independent patrons of the exposure (the base risk or Conflict of interests: declared in the article. Conflict of interests: the exposure is reinstated or the de- a restaurant. Even if the micro- BRHP - gree of exposure is increased? The organism responsible for the logic data or study. Two assump- dechallenge–rechallenge criterion is tions) isare quantified inherent via in epidemioassessing obviously unhelpful for evaluating thus biologic plausibility cannot causal associations for traumatic in- beoutbreak examined), is not the identified general plau (and- base rate is relatively consist- jury, or single exposures to drugs and sibility question is easily satis- entthe BR;over first time, that and the second, underlying that other potentially noxious substances the risk posed by the hazard is

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independent of the BR. A ba- plaintiff to the extent that the predic- HR and/or a BR. The database used sis for estimating BR may come tive characteristics of both the haz- for the analyses was the Nationwide from previously published well- ard and the plaintiff as he would have Inpatient Sample (NIS) of the Health- designed epidemiologic study, or been pre-exposure, relative to the care Utilisation Project of the Agency it may come from ad hoc analysis adverse outcome, are adequately ac- for Healthcare Research and Qual- of information from an existing counted for in the study populations. ity of the U.S. Department of Health 23 database. In many cases, the BR The two types of error that can be and Human Services . The NIS is the will be derived from annual in- made with an indirect assessment largest inpatient care database in the cidence data, and thus, in order to derive an estimate of the daily which it is concluded that there is a sample of approximately 20% of hos- or even hourly risk (depending causalof specific relationship causation when are there Type is I,not, in pitalisationsUnited States, from containing community a stratified hospi- on the HP) the annual rate must and Type II, in which it is concluded tals in the country, which amounts to

be relatively stable, or it must be that there is not a causal relationship approximately 8 million hospitalisa- when there is. It is important that a tions that are recorded annually. The description of the potential for each sampling frame for the NIS is a sam- theadjusted individual. to reflect the alteration type of error that is inherent in a ple of hospitals that comprises ap- (5) Theof base risk rate of over injury time associatedspecific to causal analysis is presented for the proximately 95% of all hospital dis- with the hazard is compared - charges in the United States. The data with the risk of injury absent the racy of the conclusion. are weighted to provide a national hazard, resulting in a ratio that fact finder to help assess the accu estimate of the annual incidence of describes comparative risk (CR), Case presentations diagnoses, treatments, outcomes - In the following section of this report and other recorded variables for pa- dence interval. CR is similar in are three case studies in which we de- tients admitted to all US community conceptwith an to associated a RR or odds 95% ratio confi and scribe serious neurologic injuries fol- hospitals. in some cases is identical, but it lowing alleged acts of negligence. The All of the statistical analyses de- differs in that it only compares cases serve as exemplars to illustrate scribed for the cases were performed substantive competing risks that the previously described method for using SAS Version 9.2; SAS Institute are relevant to the individual at Inc., Cary, NC. the time of the exposure. The causation in medical negligence legal equation for CR is actionsthe indirect in which evaluation the primary of specificdispute Case 1 HR was the CR of competing explana- Partial paralysis following alleged = CR BRHP tions for the adverse outcome, and failure to treat acute ischaemic stroke the general plausibility of the rela- with thrombolytic therapy resulting . The CR ratio is related to the at- tionship between the alleged hazard in permanent paralysis tributable risk percent, also known and the adverse outcome was pre- A 46-year-old female, with history as the probability of causation (PC), viously established. The cases are of recent transient ischaemic attack, 22 as follows : described in the following fashion: experienced sudden onset of right fa- CR −1 ×=100% PC (1) a brief history of the salient and cial droop and right-sided extremity CR undisputed facts is provided; (2) the weakness (hemiparesis). Paramedics The result of the analysis, either a alleged negligent act is described; (3) arrived 6 min later and found her on CR or PC, is compared with a stand- the opposing or defending theory is - ard of what is ‘more likely true than described; (4) the CR elements are sic). She was transported to a pri- marythe floor stroke and centre unable within to speak 1 h (apha of the >1.0 lower boundary), or a PC of the alleged hazard and adverse out- onset of symptoms, and following not’, and thus a CR of ≥2.0 (95% CI come,given, includingan assessment the identification of the HP be of- computed tomography (CT) scan of - the head that was negative for haem- entation≥50%, serves in a aslegal indirect setting. evidence A PC of manifestation of the adverse outcome orrhage, she was diagnosed with an Conflict of interests: declared in the article Conflict of interests:

>50%specific indicates causation that suitable a randomly for pres se- andtween an the estimation alleged hazard of both and the theHR firstand early ischaemic stroke in progress. . lected individual from a population The emergency department phy- of exposed and injured people would and presented as a PC. See Table 1. sician did not order thrombolytic not have the injury if the exposure theIn BR all of and the (5) cases, the an CR ad is hoc quantified analysis therapy with tissue plasminogen had not occurred, on a more prob- of data abstracted from a US national activator (t-PA). A repeat CT scan re- able than not basis. The results of the hospital database was conducted vealed a new area of acute ischaemia in order to provide an estimate of a in the distribution of the left middle analysisLicensee are applicable OA Publishing to a specific London 2014. Creative Commons Attribution License (CC-BY)

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Table 1 Causal elements in the three described case studies Case 1 Case 2 Case 3 Failure to timely treat Failure to timely diagnose and Investigated an ischaemic stroke with Cervical spine manipulation treat a brainstem herniation hazard thrombolytic agent after lumbar puncture Vertebral artery dissection and Adverse outcome Hemiparalysis Upper cervical spinal cord infarct associated stroke Injury is not predictable and Alternate hazard/ Injury would have occurred Injury was of unknown cause occurs regardless of lumbar explanation regardless of treatment and coincidental to manipulation puncture Hazard period 1.5 h 2 h 2 h Frequency of adverse outcome Frequency of adverse outcome Frequency of adverse outcome Hazard risk given no treatment given manipulation given lumbar puncture Frequency of adverse outcome Frequency of adverse outcome Frequency of adverse outcome Base risk given treatment given no treatment prior to lumbar puncture Comparative risk 2.13 to 1 163 to 1 10.8 to 1 Probability of 53 >99 91 causation (%) cerebral artery. Eighteen days later, and pregnancy. Standard logistic the patient was discharged from the access data from the NIS for women regression was used for patient with hospital to a rehabilitation unit. At agedcodes 18–50 were identifiedyears with and ischaemic used to a ‘good’ versus ‘bad’ outcome (paral- discharge, she remained aphasic and stroke discharged living in a 4-year ysis coded 0/1 vs. 2/3) and paralysed with right hemiparesis. period that culminated with the year versus not, collapsed outcome binary The plaintiff alleged that the failure of the plaintiff’s stroke (2005–2008). models. The analysis was performed to treat the patient with thrombolyt- with SAS 9.2 procedure Surveylogis- ic therapy resulted in the observed using 434.×1, t-PA administration tic to account for the complex sam- permanent neurologic sequelae, Thromboembolic stroke was defined pling design of the NIS and adjusted whereas the defence countered that outcomes of interest were paralysis for haemorrhage, coma, PTT status, the patient would have suffered the thatwas was identified categorised with as 99.10 follows: and the anticoagulant use, prior stroke, sei- permanent neurologic injury regard- 0: No paralysis zure, previous MI, hypertension and less of the thrombolytic therapy, had abnormal glucose. it been given. It was agreed by both by 344.3×, 344.4×, 344.5, 438.3×, The analysis yielded an estimated sides that the t-PA could have been 438.41: Minimal×, 438.50, paralysis438.51, 438.52. as defined 85,586 women aged 18–50 years administered within 90 min of the with ischaemic stroke admitted to US onset of the symptoms, as contrain- by 344.1, 344.2, 438.2×, 438.53. hospitals who would have been eligi- dications to administration had been 2: Moderate paralysis as defined ble for treatment with t-PA. Among ruled out by this time. 344.0×, 344.81. these women, there were 82,840 with Plausibility of the putative cause is The3: Severe following paralysis parameters as defined for by good outcome and 2,745 with a bad well established, as treatment with inclusion or adjustment were identi- outcome and 2,758 who were treated t-PA is generally accepted as improv- - with t-PA. After accounting for all of ing favourable outcome in ischaemic tions and contraindications for t-PA the contraindications for t-PA admin- stroke when administered up to 4.5 h administration,fied based on the using published the appropri indica- istration, the adjusted odds ratio of a 24–26 27 following the onset of symptoms . ate ICD-9 codes : Age < 17, intrac- good versus bad outcome when t-PA declared in the article. Conflict of interests: In order to assess the CR of the ad- ranial haemorrhage, coma, elevated was administered versus when it was verse outcome given treatment ver- partial thromboplastin time [PTT], not was 2.13 (95% CI 1.09, 4.14). sus no treatment, an analysis of data anticoagulant use, history of prior The OR of 2.13 was accepted as from the Nationwide Inpatient Sam- stroke, seizure at stroke onset, his- ple was undertaken. First, relevant tory of hypertension, abnormal glu- to a PC of 53%. As a result, it was ICD-9 diagnostic and therapeutic cose levels, myocardial infarction concludedthe case-specific that the CR most and convertedprobable

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cause of the plaintiff’s permanent The relationship was deemed - hemiparesis was the failure to ad- plausible in as much as explanation gardless of cause, was used for the CR minister t-PA. that rotation of the neck will produce estimateThis figure, in order based to on again all strokesreduce the re strain on the vertebral artery (making chance of Type I error. The annual Case 2 the injury explanation coherent). Ad- incidence equates to a BR of approxi- Manipulation of the cervical ditionally, the injury mechanism is mately 1 in 948 million during the spine followed by vertebral artery analogous to other forms of low-level 2-h HP. dissection and stroke resulting in neck trauma that have been associ- The CR resulting from this analy- permanent paralysis ated with vertebral artery dissec- sis is thus 1 in 5.8 million/1 in 948 A 28-year-old previously healthy tion28. Consistency is also present, million = 163 to 1 (95% CI 10, 2,613) as the injury has been demonstrated in favour of the manipulation as the to a chiropractor for a recent onset of consistently in a variety of popula- cause of the stroke. This value was kneemale presentedpain. As part for ofa firstthe therapyevaluation of tions exposed to the hazard29,30. Fur- converted to a PC of >99%. As a re- ther, despite some controversy, the sult, it was concluded that the most a manipulation of the cervical spine relationship is generally accepted in probable cause of the plaintiff’s ver- thatthe first included visit, therapid patient rotation underwent of the the biomedical literature as being at tebrobasilar artery dissection and head and neck. Approximately 2 h least plausibly causal31. associated stroke was the cervical following the manipulation, the pa- For the CR assessment, the risk spine manipulation. tient began to feel that the left side of dissection/stroke from a cervical of his body was numb and weak. manipulation was estimated from Case 3 The next morning his condition had the literature. Such estimates range Failure to timely diagnose and treat a worsened and he was unable to sum- from as frequent as 1 in 20,000 pa- neurologic complication of meningitis mon assistance. He was transported tients to as little as 1 in 5,846,381 resulting in spinal cord stroke and to an emergency department where manipulations32 - paralysis he was found to have left hemipare- ure was selected for the analysis to An 18-year-old previously health sis, facial paresis and dysarthria. A reduce the chance. The of Type lower I error. risk fig male college student fell ill with fever, CT angiogram of the head and neck In order to evaluate the BR of spon- chills, nausea and vomiting and over revealed a dissection of the right taneous stroke during the 2-h HP, NIS a 24-h period became incoherent and vertebral artery, and an MRI of the data were accessed for men with combative. He was transported to brain demonstrated an acute infarct vertebrobasilar stroke (ICD-9 codes a hospital and after evaluation was of the right basal ganglia. Upon dis- 433.2×) in the 25–29 age group for diagnosed with a suspected case of charge from the hospital, the patient the same year in which the stroke meningococcal meningitis. A head remained partially paralysed. The occurred (2009). These values were CT scan demonstrated oedema in the . patient had no known risk factors for compared with the number of men in brain. The following day, a lumbar stroke or arterial disease. the United States in the same year in puncture was performed on the pa- The plaintiff alleged that the ro- the same age group33. The results of - tational manipulation of the cervi- this analysis were as follows: in 2009, sis, and 2 h later his condition deteri- cal spine was performed prior to an there were an estimated 42 cases oratedtient in dramatically; order to confirm he was the agitateddiagno examination that demonstrated that of vertebrobasilar stroke among all and combative despite sedation. Af- the procedure could be performed men aged 25–29 who were admitted ter 6 h, his condition worsened fur- safely on the patient (generally ac- to US hospitals. Of note, there were ther; his pupils were unequal and he cepted best practice), and the ensu- only six cases that did not result from was not responding to painful stimu- ing improper manipulation resulted some external trauma and thus could li. A subsequent CT scan demonstrat- in a dissection of the right vertebral be considered spontaneous (20 were ed increased oedema and herniation artery, which in turn resulted in the of the base of the brain through the formation of a thrombus that embo- foramen magnum (the opening at the lised into the vertebrobasilar vascu- wereassociated due to with unarmed a traffic assault). crash, The 11 base of the skull through which the Conflict of interests: declared in the article Conflict of interests: lature and caused the subsequent samedue to year assault there with were a firearman estimated and 5 spinal cord passes). Approximate- . ischaemic stroke. 9,744,000 men of the same age liv- ly 12 h after the lumbar puncture, The defence countered with the as- ing the United States. Thus, the an- intravenous mannitol therapy was sertion that the stroke was secondary nual incidence of all vertebrobasilar initiated to reduce the intracranial to unknown factors, and the timing of stroke was approximately 1 stroke - it in relationship to the cervical ma- per 216,533 men in the 25–29 age tient was found to be a complete up- nipulation was purely coincidental. group in the United States in 2009. perpressure, cervical but quadriplegicwith no benefit. secondary The pa

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to an infarct of the high spinal cord, CR of 10.8 was converted to a PC of with no sensation or movement from interval 8.5 to 117.3). As the authors 91%, indicating that the most likely the chin down, and dependent upon providedtest; odds informationratio 32.6 (95% regarding confidence the cause was the lumbar puncture. As mechanical ventilator for respiration. frequency of herniation in the 6 h a secondary conclusion, the defence The plaintiff alleged that the failure prior to and following the lumbar theory that the spinal cord infarct to rapidly recognise and reverse the puncture, a post hoc analysis of the was unpreventable given the pres- brainstem herniation resulting from data indicated that, among those pa- ence of the brainstem compression the combination of increased intrac- tients with herniation, the condition was also rejected as unlikely. ranial pressure (evidenced by the was 10.8 times more frequent in the 6 h following puncture (95% CI 1.4, Discussion and the sudden decrease in spinal 85.2). The three cases described in this ar- canalcerebral pressure oedema following in the first the CT lumbar scan), A second approach to the CR ques- ticle give a varied but limited view puncture, was the cause of the high tion in this case was from the BR of the applicability of the methods spinal cord injury. The defence as- perspective; i.e. how likely is it that a described herein as a means of asserted that brainstem herniation is patient with a brainstem herniation a relatively common and unpredict- will suffer from a permanent injury, in medical malpractice actions. In able complication of meningitis, and including an infarct of the spinal cord allsessing the three indirect cases, specific causation causation was as such an unpredictable and unpre- with associated paralysis, or a neu- the primary contested issue, and in ventable complication, unrelated to rologic injury of similar severity, as- none of the cases was there a basis the lumbar puncture. The defence suming prompt clinical recognition - further asserted that once the brain- of the condition? ment. The medical experts on either stem compression had occurred, the An analysis of NIS data for 2000– sidefor aof direct the cases specific either causal opined assess re- adverse outcome was unpreventable. 2010 was undertaken to address this garding which of the possible causes It is widely recognised in clinical question. First, the relevant ICD-9 they deemed to be most likely (both medicine that herniation of the brain diagnostic codes for meningitis (all plaintiff and defence experts), or stem may occur during or after a lum- causes), brain compression and seri- they opined that there was no way bar puncture, and most typically in a ous adverse events, including stroke, to know which of the possible causes patient with increased intracranial was the most likely (only defence ex- pressure34. Even if it was not well doc- and then the corresponding data perts). Although in all the three cases umented, the relationship meets the wereparalysis pulled and forcoma, patients were identified,aged 30 the analysis supported the theory of coherence, consistency, plausibility, and less. The results of the analysis causation put forth by the plaintiff analogy and dose–response criteria. were as follows: there were a to- (that the allegedly negligent conduct The CR analysis in this case was tal of 684,654 hospitalised patients was the cause of the adverse out- approached from two different per- with a diagnosis of meningitis. Out of come), the methods described herein this group, there were 2,991 (0.4%) are unrelated to the side (plaintiff or perspective; i.e. if a patient with men- who were diagnosed with brainstem defendant) for which the analysis is ingitisspectives; suffers the from first wasa brainstem from hazard her- compression/herniation. Among the performed, and thus the outcome of niation following a lumbar puncture patients with brainstem compres- the analysis is, by design, non-parti- how likely is it that the complication sion, there were 345 cases of cer- san. If the underlying predictive facts was due to the procedure rather than ebral stroke (11.5% total), with 168 of the case are accurately detailed, the natural course of the disease? cases of associated hemiplegia and the confounding factors are identi- no cases of spinal cord stroke. Based was found in a previously published on this analysis, it was concluded analysis is adequately matched to the studyThe answer of the CT to scans this of first 445 questionchildren that (1) brainstem compression is a relevantfied and accountedfacts of the for, case, and thenthe data the with bacterial meningitis admitted rare complication of meningitis and results of the indirect assessment of to a large paediatric referral centre (2) when brainstem compression/ hospital35. The authors documented herniation occurs during hospitali- - time from lumbar puncture to her- sation and the condition is (presum- cationspecific of causationthe true causal described relationship herein declared in the article. Conflict of interests: niation in 19 episodes of herniation. ably) diagnosed and treated rapidly, betweenshould be the the allegedmost accurate hazard quantifi and the Twelve of the 19 herniations oc- in 88.5% of cases there is no serious adverse outcome available. adverse outcome. In these cases, and in the authors’ puncture, whereas the seven others In order to evaluate the probabil- experience generally, there is a lack occurredcurred in overthe firstsix other 10 h 10-hafter periodslumbar ity that the lumbar puncture was re- of scrutiny regarding how causal as- (P < 0.001, two-tailed Fisher’s exact lated to the brainstem herniation, the sessments are made in medicolegal

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settings. Most often, they are simply is because of prior experience with unlikely that he will suffer a stroke given by medical experts as a per- similar fact patterns, or because the (i.e. the probability of stroke given a sonally held belief as to what seems competing explanations are obvi- manipulation is low). This is not the most likely - ously quite remote. In cases in which causation question, however. ‘What tion of how likely. This approach is the initial impression is that there is is the risk of a stroke associated with often referred without to incorrectly any quantifica as the not likely to be a demonstrable caus- a manipulation?’ is a different ques- ‘differential diagnosis’ approach to al relationship, there is typically no tion than ‘the patient had a stroke causation. The name is incorrect, as subsequent analysis. Thus, the cases minutes after having a manipula- the medical expert is not differenti- that undergo a full analysis are also tion; what is the probability the ating between possible diagnoses to those cases most likely to result in manipulation was the cause of the explain a set of signs and symptoms a conclusion that is aligned with the stroke?’ It is only by comparing the in a patient; rather, the expert is interests of the party requesting the risk of the injury associated with the choosing between possible causes of analysis. This is not always the case, manipulation to the risk of the injury a diagnosis based on an assessment however, and in cases with unique due to all other causes acting on the of which cause presents the high- causation questions for which no pri- individual at the same point in time est risk. If this practice sounds like or analysis has been performed and that the meaning of a 1 in 5.8 million an intuitive or speculative approach no literature exists, the results of the risk of injury is given context for a to the evaluation of CR described in analysis may be disappointing to the causation assessment. this article, it is because that is pre- retaining party. This is not to say that the indi- cisely what it is. In all the three case The concept of CR versus RR rect method of assessing specific studies presented herein, there were is one that is largely unique to a causation described in this article medical experts who opined on CR of medicolegal application. CR con- is without potential error or weak- cause based on either personal ex- sists of a comparison between two nesses. The indirect evaluation of perience or their understanding of or more plausible causes that are specific causation is Bayesian at its previously published epidemiologic core; based on the modification or study. The courts tend to allow such case, whereas RR is a comparison conditioning of probabilities with testimony without question, in part betweenknown to exposure be present and in non-expo a specific- relevant evidence that is specific because there are no widely known sure. As a practical matter, common to the investigated case. Possible alternatives, and also because causal competing causes of injury can be causes must be considered or re- determinations are most commonly eliminated from an investigation jected in an unbiased and fair man- made by the same clinicians who di- by the medical facts in a case, and ner. A failure to consider relevant agnosed the condition in question. it is solely the opposing theories of and predictive evidence may result The lack of a systematic approach causation put forth by the plaintiff in a fatally flawed and incorrect . to causal determinations in medico- and defendant that require quanti- causation analysis. Conversely, the legal settings serves as an invitation - judgement as to what is relevant for speculation, and even abuse, giv- gency makes a CR evaluation a more and predictive in the analysis of pragmatic,fication and economical comparison. and Thisaccurate exi a specific case is by its nature a experts who provide causation testi- - subjective process, based on the monyen the in financial court. incentives to medical sation in a medicolegal setting than experience and knowledge of the A common theme in all the three RR,approach in many to evaluatingcircumstances. specific cau forensic epidemiologist. A basic cases described here is the fact that It is worth noting that a causa- understanding of the physiologic, the analysis was performed on be- tion assessment is accomplished via therapeutic and pathologic pro- half of the injured party bringing assessment of comparative, rather cesses at the centre of an alleged suit, and the result of the analysis fa- than absolute risk, and that the two act of medical malpractice is crucial voured the injured party. This should are easily confused in a legal setting. prior to embarking on an analysis not be taken as a sign of a biased or As an example, in the second case of a general or specific causation. unfair analysis, but rather repre- study described above in which a Conflict of interests: declared in the article Conflict of interests: sentative bias in the selection pro- manipulation of the cervical spine Conclusion . cess by which cases are accepted for was closely followed in time by Epidemiology is a science that is analysis. In most instances, the initial a vertebral artery dissection and primarily directed at the investiga- impression of a demonstrable causal stroke, the HR used for the CR as- tion of effects in populations given relationship gleaned from a sum- sessment was 1 in 5,846,381. Thus, known causes. FE, on the other hand, mary of the case facts is born out by it is reasonable to conclude that if is focused on the investigation of the the subsequent analysis. Often, this a patient is manipulated, it is very most probable cause given known

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