AU2004200693B2 - System and Method for Evaluating Pretest Probabilities of Life-threatening Diseases - Google Patents

Description

S&F Ref: 667251

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT Name and Address of Applicant: Actual Inventor(s): Address for Service: Invention Title: Charlotte-Mecklenburg Hospital Authority d/b/a Carolinas Medical Center P.O.Box 32861 Charlotte North Carolina 18232-2861 United States of America Jeffrey A. Kline Spruson Ferguson St Martins Tower Level 31 Market Street Sydney NSW 2000 (CCN 3710000177) System and Method for Evaluating Pretest Probabilities of Life-threatening Diseases The following statement is a full description of this invention, including the best method of performing it known to me/us:- 5845c SYSTEM AND METHOD FOR EVALUATING PRETEST PROBABILITIES OF LIFE-THREATENING

DISEASES

BACKGROUND OF THE INVENTION 1. Field of Invention The present invention generally relates to a system and method for evaluating potentially fatal diseases and, more particularly, for determining the pretest probability and confidence interval that a patient has a potentially fatal disease.

2. Description of the Prior Art 1 0 As technology produces more rapid methods of evaluating a patient's risk for contracting a life threatening disease, physicians will avail themselves of these technologies more often, leading to an increase in resource use. Owing to new research in imaging and laboratory testing over the past five years, protocols for testing patients with complaints suggestive of the possibility of a life threatening- illness in the emergency department have changed substantially at many centers. Three examples are the probability of pulmonary embolism (PE) in a patient with chest pain and/or shortness of breath, the probability of an acute coronary syndrome in a patient with anterior chest pain, and the probability of subarachnoid hemorrhage in a patient with a headache. For these conditions, emergency physicians are becoming more reliant on the use of specific tests and diagnostic protocols. For patients with possible PE, physicians can order a Ddimer assay and contrast-enhanced computerized tomography To rule out acute coronary syndrome, physicians can invoke a diagnostic protocol that includes serial blood chemistry studies and cardiac imaging. Finally, to rule out subarachnoid hemorrhage, physicians can perform CT scanning followed by lumbar puncture for evaluation of the cerbrospinal fluid. The problem with each of these examples includes increased time and cost required to complete the evaluation, and the possibility of false positive testing that can lead to more invasive and potentially more dangerous diagnostic studies and false positive diagnoses. The probability of adverse events related to false positive testing will increase in proportion to the frequency with which patients with a very pretest low probability are evaluated for these diseases.

Under the pressure of constant overcrowding and medical/legal concerns, emergency physicians are ready to embrace more rapid and streamlined systems to screen for a common and potentially fatal disease. At the same time, emergency medicine physicians are taught during residency, in the textbooks, and in continuing medical 1 5 education courses, that they must have an unwavering suspicion for the potential that every patient with chest pain, shortness of breath or headache may have an undiagnosed fatal disease process, including acute coronary syndrome, pulmonary embolism (PE) and subarachnoid hemorrhage, respectively. As a result, many physicians working in the emergency department setting maintain the position that the liberal use of screening tests is ethically and medically/legally warranted.

As a result of these influences, the frequency of objective screening for acute coronary syndromes, PE, and subarachnoid hemorrhage has increased sharply, even as U.S. emergency departments become even more overcrowded. In 1998, when the scintillation ventilation-perfusion (VQ) lung scanning was the primary mode of evaluating PE, 0.39 percent of 96,000 emergency department patients underwent a VQ scan. However, in 2000, after implementation of CT scanning as the primary method of evaluation for PE, CT scans were performed to evaluate for PE in 0.69 percent of 102,000 emergency department patients. When the PI implemented a "rapid PE rule out" system in 2001 (consisting of a decision rule plus a whole-blood D-dimer plus an alveolar deadspace measurement) the rate of screening for PE increased to 1.14% of 108,000 patients.

When physicians in Canada used a scoring system and D-dimer as the first step to screen for PE in 946 ED patients, the resulting overall probability of PE in the study was reduced to 9.5 percent (the lowest yet reported), suggesting very liberal use of testing.

Increased screening for PE may have negative consequences. A study by Goldstein et al, demonstrated that the implementation of a rapid D-dimer method to screen for PE produced a net increase in the rate of VQ scanning among inpatients.

These findings show that as technology produces more rapid and easier methods of evaluating for PE, that physicians.will avail themselves of these technologies more often, potentially leading to an increase in resource use. As the frequency of screening for PE increases in relatively low-risk groups, the number of adverse events related to contrast allergy, radiation exposure, and anticoagulant treatment of false positive cases 2 0 may increase. In other words, more rapid tests offer the option of easier evaluation for life-threatening illness, but at the risk of being overused in an extremely low-risk population. Moreover, as the rate and breadth of screening for potentially fatal disease increases in relatively low-risk groups, the number of adverse events related to contrast allergy, radiation exposure, and treatment of false positive cases will also increase.

The diagnostic accuracy of theobjective tests, such as a computed tomography xray of the chest, can be defined by their likelihood ratio. Likelihood ratios are relatively precise variables that are arithmetically defined fiom sensitivity and specificity data provided by clinical studies. Moreover, meta-analysis techniques allow the aggregation of the results of many separate studies of one test, to estimate a composite likelihood ratio negative for the diagnostic test. However, no method exists to calculate a relatively precise estimate of the pretest probability of life-threatening diseases.

Traditional methods of pretest determination of life-threatening diseases involve a particular physician's remembered cases, the use of practice databases, planned research, and population prevalence. Although remembered cases offers an immediate and constantly available method, this "gestalt" metiod lacks reproducibility and is likely to vary with training level and can be subject to bias. Practice databases and population prevalence may be helpful for a gross estimate for a patient based upon one or two symptoms, but current strategies lack the ability to provide specialized consideration of age, gender, race, vital sign data, and the mosaic of clinical data for any given patient.

The bulk of published methods for pretest assessment fall into the area of planned research. Multiple schemes and scoring systems have been devised to estimate the pretest probability of life-threatening diseases, including neural network systems scoring systems and various criteria based upon analysis of clinical factors with Boolean operators. These systems are logically designed and are relatively straight-forward to use. The drawback to existing methods of pretest assessment is that they either underfit or overfit individual patients, and only provide ranges of probability when, within each range, there exist domains of significantly different probabilities. For example, published scoring systems targeted at PE categorize up to 50 percent of ED patients as moderate risk, providing the vague assurance that the pretest probability lies between 20 to percent. Published scoring systems are also hindered by their assumption that each variable functions independently to predict the presence or absence of disease of interest, and do not allow for a tailor-made clinical profile to be developed for every patient. As a result, patients with factors that represent a true risk for PE are overlooked in the derivation of the scoring system. Additionally, these methods do not factor the complex interdependence of predictors on the probability of the disease.

It is therefore desirable to provide physicians with an accurate method of evaluating a patient for the probability of the presence of a potentially life-threatening disease.

It is further desirable to provide a method for determining the probability of certain outcomes of a potentially life-threatening disease, including degree of severity of the disease and the probability of death within a defined interval.

It is further desirable to provide a method of evaluating a patient for the probability of the presence of a potentially life-threatening disease which reduces the likelihood of unnecessary diagnostic testing.

It is further desirable to provide physicians with a method for evaluating a patient for the probability of the presence of a potentially life-threatening disease which incorporates numerous clinical factors that can be obtained by routine clinical interview and physical examination.

It is further desirable to reduce the number of incorrect diagnoses.

It is further desirable to determine the probability of certain adverse outcomes which mandate emergent treatment or intervention.

It is further desirable to improve the documentation of cases histories to reduce or eliminate associated malpractice issues.

It is the object of the present invention to substantially overcome or at least ameliorate one or more of the disadvantages of the prior art or to meet one or more of the above desires.

Summary of the Invention Accordingly, in a first aspect, the present invention provides a method for determining a patient's pretest probability for a life-threatening disease, comprising the steps of: [R:\LIBLL] 1 8284.doc:lzv collecting reference data comprising a plurality of clinically relevant patient 0 parameters from a plurality of individuals previously tested for said disease; storing said reference data in a database; tcollecting clinical data from said patient; s comparing said clinical data to said reference data and determining the percentage of said individuals with matching parameters to said patient; determining the percentage probability of said patient having said disease based on said comparison; and IN displaying said percentage probability.

In a second aspect, the present invention provides a method for determining a patient's pretest probability for a life-threatening disease using reference data previously Ocollected from a plurality of individuals previously tested for said disease, comprising the steps of: collecting clinical data from said patient; comparing said clinical data to said reference data and determining the percentage of said individuals with matching parameters to said patient; determining the percentage probability of said patient having said disease based on said comparison; and displaying said percentage probability.

In a third aspect, the present invention provides a system for determining a patient's pretest probability for a life-threatening disease, comprising: means for collecting reference data comprising a plurality of clinically relevant patient parameters from a plurality of individuals previously tested for said disease; means for storing said reference data in a database; means for collecting clinical data from said patient; means for comparing said clinical data to said reference data and determining the percentage of said individuals with matching parameters to said patient; means for determining the percentage probability of said patient having said disease based on said comparison; and means for displaying said percentage probability.

In a fourth aspect, the present invention provides a system for determining a patient's pretest probability for a life-threatening disease, using reference data previously collected from a plurality of individuals previously tested for said disease, said system comprising: means for collecting clinical data from said patient; 6 [R:\LIBLL] I 8284.doc:lzv means for comparing said clinical data to said reference data and determining the O percentage of said individuals with matching parameters to said patient; C' means for determining the percentage probability of said patient having said tdisease based on said comparison; and means for displaying said percentage probability.

Brief Description of the Drawings rc A preferred form of the present invention will now be described by way of Nexample with reference to the accompanying drawings, wherein: Fig. 1 a flowchart of the method of the present invention.

(N Fig. 2 is an example of an electronic data form for use with the present invention.

Fig. 3 is a flowchart of a hypothetical determination of pretest probability (Ni according to the present invention.

Fig. 4 is a flowchart of an additional embodiment of the present invention.

Detailed Description Although this description refers to a pulmonary embolism (PE) as the primary disease, the method and system of the present invention may be used to predict the pretest probability of other disorders, including but not limited to, acute coronary syndrome and subarachnoid haemorrhage. The invention will also be applied to evaluate the probability of certain life-threatening diagnoses or other clinical outcomes in patients with symptoms or complaints, including, anterior chest pain, headache, syncope, symptoms consistent with transient ischemic attack, fever, minor head injury, shortness of breath, seizure, altered mental status, abdominal pain, trauma, dizziness, weakness, high blood pressure, and low blood pressure.

Referring now to the drawings in which like numerals refer to like parts through out, there is seen in Fig. 1 a flow chart of the method of present invention for determining a particular patient's pretest probability 10 for PE. Prior to starting the process for 7 [R:\LIBLL] I 8284.doc:lzv determining pretest probability 10 for a particular patient, however, it is necessary to create a reference database 20 containing clinical data for a sample population previously tested for PE which is then stored in reference database The collection of reference data 40 for reference database 30 may be performed by a variety of conventional methods, such as entering the information from a patient's Smedical history directly into a computer database. Alternatively, the present invention contemplates the use of an electronic form 50 programmed as part of an application for use, for example, on a personal digital assistance (PDA).

As seen in Fig. 2, electronic form 50 contains entry lines for a wide variety of information, from patient background information to specific clinical data relevant to diagnosis of a particular disease, such as a PE in the example case. A physician enters the answers to the numbered questions on electronic form 50 as they are obtained directly from the patient or from the patient's medical records.

Electronic form 50 is designed to allow very quick and easy input at the bedside.

1 5 The content and number of fields in the form elicit data, which represent the pretest parameters that are immediately available at the bedside, including results of 12-leadelectrocardiography. The prospective parameters that are included have previously been demonstrated to be important to the diagnosis and exclusion -of PE based upon patient samples from emergency departments in the United States, Canada and Switzerland.

2 0 Because electronic form 50 may be filled out in real-time in the PDA, its format allows the rapid entry of the key information that is most likely to help distinguish patients with PE from those without PE while minimizing the time requirement to enter the information.

After docking of the PDA containing electronic form 50 to a cradle device or other electronic means, newly created or updated electronic forms 50 are uploaded to a central computer or designated website programmed to assimilate and analyze the reference data 60. Electronic form 50 may alternatively be used to collect data from prospectively studied patients, retrospectively studied patients who were previously evaluated for PE, retrospectively studied patients with PE who were known to have been evaluated by a physician who failed to diagnose PE including patients who were the subject of civil litigaion. It should be understood that the database can be built firom as many sources as are required to provide sufficient reference data to establish a statistically significant database.

It is anticipated that a different database will be established to evaluate for the pretest probability.ofPE, acute coronary syndrome, subarachnoid hemorrhage and other life-threatening diseases. Separate databases will be assimilated to determine the probabilities of certain life-threatening diseases or outcomes for specific complaints, symptoms or signs including, anterior chest pain, headache, syncope, neurological symptoms consistent with transient brain ischemia, fever, minor head injury, shortness of breath, seizure, altered mental status, abdominal.pain, trauma, dizziness, weakness, high blood pressure, and low blood pressure.

Once an accurate reference database 30 has been established, pretest probability 10 can be calculated from a personal computer or a personal digital assistant (PDA) which can access reference database 30 and which is programmed to perform a comparison of the patient data 70 to reference database 30. As seen in Fig. 1, patient data 62 is first obtained from the patient whose pretest probability 10 Ois to be determined. The data may comprise the same information which was obtained via electronic form 50 and used to compile the reference database, or may comprise only the most relevant, "cardinal" characteristics indicative of PE as determined by assimilating and analyzing the reference data 60. For example, multivariate logistic regression analysis-or classification and regression tree analysis will be performed on reference database 30 to determine which parameters should be included as cardinal data to be used to estimate the probability of PE. Cardinal parameters may include continuous data, such as body mass index, age, gender, and vital signs as well as categorical data, such as gender, race, 1 0 and the presence or absence of other factors.

Once patient data 60 is obtained, it is compared 70 to the reference database 30 to return matching reference patient data, reference patients with corresponding data points stored in reference database 30. Comparison 70 begins by taking the patient's individual data points, age, pulse rate, respiratory rate, systolic blood pressure, pulse 1 5 oximetry, and temperature, and establishing a clinically relevant interval for each.

Clinically relevant intervals are a given range for continuous data parameters. For example, patient age may be broken into 0-30 years, 31-45 years, 46-65 years, etc. The number and width of the intervals for each relevantparameter will be chosen based upon a histogram plot of the frequency probability) of the disease versus the parameter.

The width of the interval for each continuous parameter will be set to contain no more than 33.3% of the total number of patients in the database who are disease positive. The width of the interval will vary with the specific parameter, the size of the reference database, and the frequency of the disease in the reference database population. A match is determined by searching the database to see whether any reference patients in reference database 30 have a data point within the interval established for that parameter based upon data from the new patient for whom the pretest probability is unknown.

The cardinal parameters are expected to include, but not be limited to, symptoms dyspnea, chest pain location, syncope, cough with hemoptysis, cough without hemoptysis), findings unilateral leg swelling and wheezing on auscultation of the lungs), and risk factors prior pulmonary embolism, recent surgery, malignancy, oral contraceptive use, pregnancy, and post partum status) and alternative processes smoking, history of asthma, history of COPD, or other chronic lung disease). The patient is matched unconditionally to these cardinalparameters.

The patient may also be matched to additional data, termed "conditional'" parameters, also recorded for each patient within reference database 30. Conditional parameters will have less importance in predicting the pretest probability according to the multivariate regression or classification and regression tree analysis. Conditional parameters significantly reduce the number of patients in the database that yield a match, As a result, pretest probability 10 can determined with and without conditional matches.

A large disparity between the pretest probability estimate using only cardinal parameters compared with the pretest probability obtained by matching of cardinal plus Sconditional parameters may indicate that the results of the former are not reliable. If in addition, the 95% confidence intervals for the pretestprobability estimate from the cardinal plus conditional parameter match is very wide (e.g the results of the pretest probability estimate should be considered invalid for clinical decision-making.

For the estimation of the pretest probability of PE, parameters that are likely to fall into the conditional category include, but are not limited to, duration of symptoms, the first symptom experienced, whether the patient has sought medical attention for the same complaint recently, body mass index, pregnancy, post-partum status, the presence or absence of sickle cell disease, connective tissue diseases, known coronary artery disease, congestive heart failure, family history of clots, estrogen replacement therapy, and history.

of anxiety or fibromyalgia.

By returning matching reference patients 72 using cardinal and conditional parameters, two pretest probabilities 80 with successivelymore exact matching and a decreasing number of matches can be determined. Thus, the application of method of the present invention will show the trade-off between precision of clinical matching and precision of the point estimate for pretest probability (based upon the 95% confidence interval). The first estimate will return the largest number of patients, matched for age and vital sign intervals, and exactly for cardinal features. The second will be all patients in the first group subjected to more exact matching for conditional variables.

Calculating the pretest probability and confidence interval 80 uses the traditional 0 method to compute a 95% confidence interval. Ifx equals the number of subjects matched to a new patient and d equals the number of those matched subjects previously determined to have the disease in question, then the proportion of subjects with the disease and the proportion of subjects without the disease is calculated as follows: p= d/x q=l-p The standard error is determined according to the formula: SE(p) q)/4x The formulas for calculating the upper and lower levels of the confidence intervals using a 95 th percentile critical ratio from the normal distribution (1.96) are determined, respectively, as follows: p [1.96 SE(p)] p- [1.96 SE(p)] If d is less than 5 or if x d is less than 5, then the "exact" methods as described by Newcomb and Altman, Chapter 6, Proportions and Their Differences in Statistics with Confidence, 2 nd ed. (BMJ, Bristol, UK), hereby incorporated by reference; may be used.

Alternatively, using modification of the above formulae, other confidence intervals can be selected by the user, including a 99% confidence interval or the computation of the Bayesian credible interval. Once the pretest probability and associated confidence intervals are calculated 80, the results are displayed for the treating physician.

Additionally, the query and results may be stored 110 along with date and time Stamps to accurately record the entire pretest probability 10 process in permanent electronic 1 5 storage.

As seen in Fig. 4, reference database 30 can further be configured to return other important outcome data for use in calculating probabilities helpful to a physician. This data, in conjunction with calculated pretest probability 90, may be used to calculate posttest probabilities 120, the percentage of like patients who experienced death within days of diagnosis 140, and the percentage of like patients who were ultimately diagnosed with another clinically important disease besides the disease under primary consideration 170. For example, the returned resultscould include the number of patients in the matched set who were diagnosed with a myocardial infarction as opposed to PE.

For the purpose of calculating the post-test probability 120 of PE, the PDA or electronic device can be preprogrammed with published likelihood ratio data 110 for multiple tests, and the clinician can choose the test that he or she is considering. These tests include, but are not limited to, the D-dimer assay, contrast-enhanced computerized tomography angiography of the chest, scintillation ventilation-perfusion lung scanning (broken down into four results), echocardiography, normal plain film chest radiograph, normal alveolar deadspace measurement, and normal arterial oxygen partial pressure.

The post-test probability 120 (postP) of a disease is calculated by first obtaining the pre-test probability 90 (PreP) according to the present invention. The likelihood ratio negative (LRn) for a negative test result is calculated from published sensitivity and specificity data for the selected test according to the following formula: LRn sensitivity)/specificity The pre-test odds (PreO) and post-test odds (PostO) are then be calculated as follows: PreO =PreP/ PreP) PostO PreO LRn Finally, post-test probability 120 may be.determined according to the following formula: PostP PostO (PostO 1) 2 0 The probability of death may be calculated using the instances of death within the matching reference patient data 72. For example, the present invention can report the percentage of matched patients tested for PE who survived for three or more months without sequelae. If a physician desires, he or she can use matching reference patient 72 to determine the probability of adverse outcomes that would mandate specific treatment had the outcome been foreseen at the time of patient presentation. For example, for a patient with anterior chest pain, the present invention can report the percentage of matched patients from a chest pain reference database that required acute percutaneous coronary revascularization. The calculated probabilities for any or all of the these additional calculations 120, 140, 170 may be displayed 190 and stored in memory 200 with time and date stamps for future uploading to a server or an associated network storage device.

Fig. 3 depicts a clinical example of a linear comparison to a hypothetical reference database according to the method of the present invention for determining the probabilities associated with of a specific disease, PE. The patient in the example is a 57 year old white female with history of PE one year prior, presents with shortness of breath starting yesterday, nonproductive cough for one week and sudden onset pleuritic chest pain "exactly like" the previous PE last year. She smokes cigarettes and has been previously told she has the condition of fibromyalgia. She takes estrogen replacement therapy for hot flashes. Her vital signs are as follows: pulse 103, respiratory rate 28, sBP 141, Sa02% 98%, and no leg swelling.

Figure 3 also depicts the process of matching six successive continuous parameters from an unknown patient to the database, age, pulse oximetry (Sa02%), heart rate respiratory rate systolic blood pressure (sBP), and temperature (Temp).

These parameters, their order, and the number and width of intervals for each parameter are shown for the purpose of describing the operation of the present invention and do not necessarily represent the order or criteria that will be used in actual practice.

As shown, the patient data is sorted and compared to the reference database, hypothetically containing 1,500 previously studied patients. The example patient is matched to patients in the database who also fall within the predetermined ranges shown.

(a match is represented by the darkened ovals). In this example, the process of matching the patient's age and vital signs has narrowed the number of patients in the hypothetical database down to 105 patients who have recorded clinical data similar to that of the sample patient.

The number of matches is further narrowed by matching considering the following data (with the hypothetical patient data in parenthesis): dyspnea (yes), syncope substemal chest pain pleuritic chest pain (yes), non-productive cough (yes), hemoptysis oral contraceptives prior PE or DVT (yes), active malignancy (no), recent Surgery immobility smoker (yes), asthma, COPD or other chronic lung disease unilateral leg swelling and wheezing Consideration of these factors returns fifteen patients out of the 105 who had all of the cardinal parameters 1 5 exactly the same as the patient's cardinal parameters. If one of the fifteen matches was ultimately diagnosed with PE, the example patient's pretest probability will be onefifteenth or 6.7 percent, with a 95 percent confidence interval of zero to 32 percent, using the aforementioned formulae. Consideration of conditional variables narrows the number matcheseven further, returning a smaller set of patients perhaps five) who are even more similar to the example patient.

The post-test probabilities of PE if the patient undergoes a CT scan of the chest, can be determined from the hypothetical results as follows. Assuming a likelihood ratio negative of 0.1 and likelihood ratio positive of 10, the post-test probability of PE after a negative CT scan would be 0.75% and the post-test probability of PE if the CT scan is positive would be 43%. The present invention may provide this computation for all other diagnostic tests with published likelihoods that are pertinent to the evaluation of the disease in question.

Claims (21)

1. A method for determining a patient's pretest probability for a life-threatening disease, comprising the steps of: collecting reference data comprising a plurality of clinically relevant patient parameters from a plurality of individuals previously tested for said disease; storing said reference data in a database; collecting clinical data from said patient; comparing said clinical data to said reference data and determining the percentage of said individuals with matching parameters to said patient; determining the percentage probability of said patient having said disease based on said comparison; and displaying said percentage probability.

2. The method of claim 1, further comprising the step of storing the input data and 1 5 probabilityresults in electronic memory.

3. The method of claim 1, further comprising the step of analyzing said reference data to determine the probability of death during a predetermined time interval.

4. The method of claim 1, further comprising the step of analyzing said reference data to determine the probability of an alternative life-threatening disease process.

The method of claim 1, further comprising the step of analyzing said reference data to determine the probability of other outcomes that mandate emergent treatment or intervention related to the degree of severity of the disease in question.

6. The method of claim 1, further comprisingthe step of analyzing said reference data to determine the percentage of patients in the reference database matched to the unknown patient who underwent relevant treatments.

7. The method of claim 1, further comprising the step of analyzing said reference data to determine the probability of a favorable outcome.

8. The method of claim 1, further comprising the step of analyzing said reference data to determine the relative significance of each of said patient statistics.

9. The method of claim 1, further comprising the step of computing the expected post- test probabilities for said disease using published likelihood ratio data for clinical diagnostic tests commonly used to test for said disease.

The method of claim 1, wherein the step of determining the percentage probability of said patient having said disease further comprises determining the upper and lower confidence intervals for said probability based ona predetermined confidence interval.

11. The method of claim 1, wherein said life-threatening disease is a pulmonary embolism.

12. The method of claim 5, wherein the predetermined confidence interval is ninety-five percent.

13. A method for determining a patient's pretest probability for a life-threatening disease using reference data previously collected from a plurality of individuals previously tested for said disease, comprising the steps of: collecting clinical data from said patient; comparing said clinical data to said reference data and determining the percentage of said individuals with matching parameters to said patient; determining the percentage probability of said patient having said disease based on said comparison; and displaying said percentage probability.

14. A system for determining a patient's pretest probability for a life-threatening disease, comprising: means for collecting reference data comprising a plurality of clinically relevant 2 0 patient parameters from a plurality of individuals previously tested for said disease; means for storing said reference datain a database, means for collecting clinical data from said patient; means for comparing said clinical data to said reference data and determining the percentage of said individuals with matching parameters to said patient; means for determining the percentage probability of said patient having said disease based on said comparison; and means for displaying said percentage probability.

A system for determining a patient's pretest probability for a life- threatening disease, using reference data previously collected from a plurality of individuals previously tested for said disease, said system comprising: means for collecting clinical data from said patient; means for comparing said clinical data to said reference data and determining the percentage of said individuals with matching parameters to said patient; means for determining the percentage probability of said patient having said disease based on said comparison; and means for displaying said percentage probability.

16. The system of claim 15, wherein said means for collecting comprises a personal digital assistant programmed with an electronic form for assembling data about a plurality of predetermined parameters.

17. The system of claim 15, wherein said means for comparing comprises a computer processor programmed to match said clinical data with said reference data. 21 [R:\LIBLL] 1 8284.doc:lzv

18. The system of claim 15, wherein said means for determining comprises a computer processor programmed to calculate a ninety-five percent confidence interval.

19. The system of claim 16, wherein said means for displaying comprises a personal digital assistant having a screen which is programmed to display said percentage probability on said screen.

A method for determining a patient's pretest probability for a life threatening disease, said method being substantially as hereinbefore described with reference to Figs. 1 to 3; or Fig. 4 of the accompanying drawings.

21. A system for determining a patient's pretest probability for a life threatening disease, said system being substantially as hereinbefore described with reference to Figs. 1 to 3; or Fig. 4 of the accompanying drawings. Dated 20 February, 2004 Charlotte-Mecklenburg Hospital Authority d/b/a Carolinas Medical Center to Patent Attorneys for the Applicant/Nominated Person SPRUSON FERGUSON 23 [R:\LIBTT]03563.doc:hxa