DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
Applicant has submitted the following:
Claims 1, 3-8, 10-15, and 17-20 are pending examination;
Claims 1, 3, 6, 8, 10, 14, 15, 17, and 20 are newly amended;
Claims 2, 9, and 16 are newly cancelled.
Response to Arguments
Applicant's arguments filed 10/21/2025 have been fully considered but they are not fully persuasive.
Applicant argues that newly amended independent claims 1, 8, and 15, with regard to rejection under 35 USC 101, amounts to an improvement in technology, and therefore integrates the abstract idea into a practical application.
Examiner finds the argument persuasive. The newly amended limitations “operating a laboratory analyzer to obtain a first measurement of an analyte of an outpatient”, “calibrating the laboratory analyzer in response to determining the standard deviation is greater than the threshold standard deviation resulting in a calibrated laboratory analyzer”, and “operating the calibrated laboratory analyzer on further instances of the analyte” of claims 1 and 15; and “a laboratory analyzer configure to obtain a measurement of an analyte of an outpatient”, and “an alert module that issues an alert indicating the laboratory analyzer that performed the first and second measurements needs to be re-calibrated based on the comparison” of claim 8 integrate the judicial exception into a practical application.
The rejection under 35 USC 101 is therefore withdrawn.
Applicant argues that newly amended claim 20 overcomes the rejection under 35 USC 112.
Examiner finds the amendment sufficient to overcome the rejection, and the rejection under 35 USC 112 is withdrawn.
Applicant argues that none of the prior art, alone or in combination, teaches the limitations of newly amended independent claims 1, 8, and 15. Specifically, Applicant argues that previously cited Cembrowski does not teach the method of claim 1, wherein the analyte analyzed is from an outpatient, and wherein the time delta is “an integer multiple of seven days and within a specified time of day window”. Applicant further argues that Cembrowski’s “specified time window” is a singular “filter”, as opposed to the two simultaneous “filters” of an integer multiple of seven days and within a specified time window.
Examiner respectfully disagrees. Cembrowski teaches an analogous method comprising determining where the time delta is an integer multiple of days (Fig. 2 step 206; [0025] “Many laboratory tests are repeated (e.g., hourly, every day, or other time frame between tests). Patients who have repeat testing at most every day (e.g., somewhere between sixteen and thirty-two hours between analyte collection) are probably quite stable and are not being aggressively treated. These patients and their corresponding measurements can provide a basis for analyzing whether an operating laboratory analyzer needs recalibration or needs to be further investigated, repaired, and/or recalibrated.”) and within a specified time of day window (Fig. 2 step 206; [0023] “Stability in the laboratory results of hospital patients can be seen in patients that are sampled (and analyzed) only once per day, such as between 0400 and 1200 hours in many hospitals. This stability arises from at least two different independent mechanisms: 1) for many laboratory tests, there is an implicit diurnal variation, so sampling and analyzing them on a 24 hour basis will tend to cause the least variation in their sequential results; and 2) in hospitals, patient acuity of illness is associated with more frequent testing. Thus, generally, only more stable patients will be sampled about once per 24 hours. The testing can occur in the morning because of requirements for tests in the fasting status and clinicians usually perform their testing rounds in the morning and require “fresh” laboratory results to help them determine the medical course of the patient.”).
However, even if Cembrowski does not teach the method comprising analyte of an outpatient, wherein the time delta is an integer multiple of seven days, said method is known in the art.
Newly cited Parvin et al. (US 20060129345 A1) teaches an analogous method for analyzing (Abstract) analyte ([0080] lines 6-8, “parameters are set for the frequency and character (e.g., number of QC test samples) of routine QC testing for each test (e.g., analyte).”) of an outpatient ([0091] “An identifier or other information uniquely identifying the instrument from which the data is preferably provided. If multiple instruments of the same type are used, they can be treated as a single instrument if they all process similar patient samples. However if one instrument is used for stat requests and another for routine requests, or if one serves outpatient testing and another serves emergency department patients, etc., then the patient results for each instrument are preferably analyzed separately.”), wherein the time delta is an integer multiple of seven days and within a specified time of day window ([0024] “Time of day and day of the week are used to further characterize patient population data to calculate a z-score for use by the EWMA (or CUSUM) model.”;[0080] lines 15-23, “Another configuration step includes establishing a patient data QC protocol for each test, e.g., by truncating time-interval patient data and determining a mean and standard deviation of the remaining data population by hour of day and day of week. The QC rule (e.g., EWMA) is then optimized for accepting normalized patient data to monitor the analytical process for each test. Another configuration step includes setting parameters for confirmation testing for each test.”; [0548] “Any statistical model using patient data for analytical process control should account for the time that testing occurs (hour of the day combined with day of the week or month).”).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 3-8, 10-15, and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over in Cembrowski (US 20160370394 A1, previously cited) view of Parvin et al. (US 20060129345 A1)
Regarding claim 1, Cembrowski teaches A method comprising:
operating a laboratory analyzer (laboratory analyzer 102) to obtain a first measurement ([0064] “Example 6 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-5 to include or use, wherein the consecutive measurements include a first measurement and a second measurement and the method further comprises comparing the second measurement to a range of acceptable measurement values and discarding the second measurement if the second sample is not within the range of acceptable measurement values.”) of an analyte (analyte 106) of a patient ([0037] lines 8-17, “The laboratory analyzer 102 can take an analyte 106 as an input and produce a result 108 that is a measurement of a property (e.g., height, width, volume, area, concentration, pH, or the like) of the analyte 106. The result 108 can be provided to the AoD module 104. The result 108 can include a tag that indicates the patient identity that the result 108 is associated with. The result can include a tag that indicates a time the analyte 106 was obtained from the patient.”), the analyte including one of albumin, alanine aminotransferase (ALT) ([0051] lines 1-4, “FIG. 6 illustrates, by way of example, a graph 600 of delta values vs. time for twenty-five days of measurements of an ALT analyte performed using a laboratory analyzer.”), aspartate aminotransferase (AST), bicarbonate, calcium, chloride, creatinine, phosphate (PO4), potassium, sodium, bilirubin (bili), protein composite, urea, or cholesterol;
determining a time delta between consecutive measurements, including the first measurement and a second measurement (Example 6 of [0064]; Fig. 2, step 205) of the analyte (analyte 106) made on the patient ([0037] lines 8-17, “The laboratory analyzer 102 can take an analyte 106 as an input and produce a result 108 that is a measurement of a property (e.g., height, width, volume, area, concentration, pH, or the like) of the analyte 106. The result 108 can be provided to the AoD module 104. The result 108 can include a tag that indicates the patient identity that the result 108 is associated with. The result can include a tag that indicates a time the analyte 106 was obtained from the patient.”) using the laboratory analyzer (laboratory analyzer 102);
determining whether the time delta is within an integer multiple of (Fig. 2 step 206; [0025] “Many laboratory tests are repeated (e.g., hourly, every day, or other time frame between tests). Patients who have repeat testing at most every day (e.g., somewhere between sixteen and thirty-two hours between analyte collection) are probably quite stable and are not being aggressively treated. These patients and their corresponding measurements can provide a basis for analyzing whether an operating laboratory analyzer needs recalibration or needs to be further investigated, repaired, and/or recalibrated.”) and within a specified time of day window (Fig. 2 step 206; [0023] “Stability in the laboratory results of hospital patients can be seen in patients that are sampled (and analyzed) only once per day, such as between 0400 and 1200 hours in many hospitals. This stability arises from at least two different independent mechanisms: 1) for many laboratory tests, there is an implicit diurnal variation, so sampling and analyzing them on a 24 hour basis will tend to cause the least variation in their sequential results; and 2) in hospitals, patient acuity of illness is associated with more frequent testing. Thus, generally, only more stable patients will be sampled about once per 24 hours. The testing can occur in the morning because of requirements for tests in the fasting status and clinicians usually perform their testing rounds in the morning and require “fresh” laboratory results to help them determine the medical course of the patient.”). The time delta is determined to be within a specified range at step 206, wherein the specified number of days is “every day or other time frame between tests” (i.e. the specified number of days is 0 or 1 for every day, or otherwise for other time frames), and wherein the specified time of day window is such time as “morning” or “between 0400 and 1200 hours”. One of ordinary skill in the art would recognize that the specified time window taught by Cembrowski (e.g. between sixteen to thirty-two hours) includes a combination of specified number of days window (0-1 days, wherein 1 day is 24 hours) and specified time of day window (wherein the residual hours remaining after 24 hour day is factored indicate the time of day, i.e. ±8 hours from 24 hour day);
determining a measurement value delta between the first and second measurements if the time delta is the integer multiple of within the time of day window (Fig. 2, step 212; [0039] lines 10-15, “If the time delta between consecutive results for the same patient is outside of the time delta range, the filter 110 can remove the value(s) or the delta corresponding to the value(s) from the results to be used by the AoD module 104 to calculate the AoD.”);
calculating an average of deltas (AoD module 104), the average of deltas including a measurement value delta between the consecutive measurements ([0038] lines 1-5, “The AoD module 104 can determine an AoD of the results 108. The AoD module 104 can include a filter 110. The filter 110 can implement a value delta filter and/or a time delta filter that filters based on consecutive analyte results from the same patient.”). AoD is the average of deltas;
determining the average of deltas is within a specified range of acceptable average of delta values ([0041] lines 1-6, “The compare module 114 compares the AoD 112 to one or more AoD thresholds 116. The AoD threshold 116 defines acceptable AoD values. If the compare module 114 determines that the AoD 112 is not within the range of acceptable values, an indicator signal can be provided to an alert module 118.”);
determining whether a standard deviation of a plurality of consecutive average of delta values is greater than a threshold standard deviation value ([0065] Example 7 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-6 to include or use, wherein determining whether the average of deltas is within a specified range of acceptable average of delta values includes comparing a standard deviation of a plurality of consecutive average of delta values to a threshold standard deviation value and the method further comprises determining the laboratory analyzer is to be calibrated in response to determining the standard deviation is greater than the threshold standard deviation.) ;
calibrating the laboratory analyzer ([0013] lines 3-5, “Laboratory analyzers may be calibrated with calibrating solutions where the calibration can be verified by an analysis of quality control specimens.”) in response to determining the standard deviation is greater than the threshold standard deviation resulting in a calibrated laboratory analyzer ([0065] Example 7 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-6 to include or use, wherein determining whether the average of deltas is within a specified range of acceptable average of delta values includes comparing a standard deviation of a plurality of consecutive average of delta values to a threshold standard deviation value and the method further comprises determining the laboratory analyzer is to be calibrated in response to determining the standard deviation is greater than the threshold standard deviation.); and
operating the calibrated laboratory analyzer on further instances of the analyte ([0013] lines 5-16, “ If the laboratory analyzer returns the value that is expected for the control specimen within a specified tolerance, then the laboratory analyzer is considered calibrated. If not, then operation of the laboratory analyzer is investigated, possibly repaired, and may be re-calibrated so that the analyzer returns quality control results within the specified tolerance. On such systems, once the analysis of one or more quality control specimens confirms that an analytical run is accurate, the laboratorian generally assumes that the prevalence of analytically defective testing is very low.”). The laboratory analyzer, being considered calibrated such that re-calibration, investigation, and/or repair is no longer necessary for accurate results, is operated as a calibrated laboratory analyzer on further instances of the analyte.
Cembrowski does not teach the method comprising:
operating a laboratory analyzer to obtain a first measurement of an analyte of an outpatient;
determining whether the time delta is an integer multiple of seven days and within a specified time of day window
Parvin teaches an analogous method comprising:
operating a laboratory analyzer ([0809] “Patient data: Result(s) derived from laboratory analysis of, e.g., human serum, plasma, whole blood, urine, spinal fluid, etc.: test result.”) to obtain a first measurement of an analyte ([0080] lines 6-8, “parameters are set for the frequency and character (e.g., number of QC test samples) of routine QC testing for each test (e.g., analyte).”) of an outpatient ([0091] “An identifier or other information uniquely identifying the instrument from which the data is preferably provided. If multiple instruments of the same type are used, they can be treated as a single instrument if they all process similar patient samples. However if one instrument is used for stat requests and another for routine requests, or if one serves outpatient testing and another serves emergency department patients, etc., then the patient results for each instrument are preferably analyzed separately.”);
determining whether the time delta is an integer multiple of seven days and within a specified time of day window ([0024] “Time of day and day of the week are used to further characterize patient population data to calculate a z-score for use by the EWMA (or CUSUM) model.”;[0080] lines 15-23, “Another configuration step includes establishing a patient data QC protocol for each test, e.g., by truncating time-interval patient data and determining a mean and standard deviation of the remaining data population by hour of day and day of week. The QC rule (e.g., EWMA) is then optimized for accepting normalized patient data to monitor the analytical process for each test. Another configuration step includes setting parameters for confirmation testing for each test.”; [0548] “Any statistical model using patient data for analytical process control should account for the time that testing occurs (hour of the day combined with day of the week or month).”).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Cembrowski to include the measurement of analyte of an outpatient and the time delta being an integer multiple of seven days and within a specified time of day window of Parvin because it would yield advantageous results, including calibrating laboratory analyzers based off of measurements of outpatients (who would not remain on a facility to be monitored) and across longer time deltas, thereby increasing the accuracy for calibration for timeframes on longer or different scales.
Regarding claim 3, Cembrowski in view of Parvin teaches The method of claim 1, wherein the specified time of day window includes the second measurement being within six hours of a same time of day as the first measurement (Cembrowski: [0061] “Example 3 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-2 to include or use, wherein the specified time window is between about eighteen and thirty hours.”). The time delta range being between 18 and 30 hours (which is ±6 hours from the 24 hour day) is within six hours of the same time of day as the first measurement.
Regarding claim 4, Cembrowski in view of Parvin teaches The method of claim 3, wherein the specified time of day window includes the second measurement being within four hours of the same time of day as the first measurement (Cembrowski: [0062] “Example 4 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-3 to include or use, wherein the specified time window is between about twenty and twenty-eight hours.”). The time delta range being between 20 and 28 hours (which is ±4 hours from the 24 hour day) is within four hours of the same time of day as the first measurement.
Regarding claim 5, Cembrowski in view of Parvin teaches The method of claim 4, wherein the specified time of day window includes the second measurement being within two hours of the same time of day as the first measurement ([0063] “Example 5 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-4 to include or use, wherein the specified time window is between about twenty-two and twenty-six hours.”). The time delta range being between 22 and 26 hours (which is ±2 hours from the 24 hour day) is within four hours of the same time of day as the first measurement.
Regarding claim 6, Cembrowski in view of Parvin teaches The method of claim 1, further comprising comparing the second measurement to a range of acceptable measurement values and discarding the second measurement if the second measurement is not within the range of acceptable measurement values (Cembrowski: [0064] “Example 6 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-5 to include or use, wherein the consecutive measurements include a first measurement and a second measurement and the method further comprises comparing the second measurement to a range of acceptable measurement values and discarding the second measurement if the second sample is not within the range of acceptable measurement values.”).
Regarding claim 7, Cembrowski in view of Parvin teaches The method of claim 1, wherein determining whether the average of deltas is within a specified range of acceptable average of delta values includes comparing a standard deviation of a plurality of consecutive average of delta values to a threshold standard deviation value and the method further comprises determining the laboratory analyzer is to be calibrated in response to determining the standard deviation is greater than the threshold standard deviation ([0065] Example 7 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-6 to include or use, wherein determining whether the average of deltas is within a specified range of acceptable average of delta values includes comparing a standard deviation of a plurality of consecutive average of delta values to a threshold standard deviation value and the method further comprises determining the laboratory analyzer is to be calibrated in response to determining the standard deviation is greater than the threshold standard deviation.).
Regarding claim 8, Cembrowski teaches A system (Fig. 1) comprising:
a processor (Fig. 8, processor 802);
a laboratory analyzer (laboratory analyzer 102) configured to obtain a measurement ([0064] “Example 6 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-5 to include or use, wherein the consecutive measurements include a first measurement and a second measurement and the method further comprises comparing the second measurement to a range of acceptable measurement values and discarding the second measurement if the second sample is not within the range of acceptable measurement values.”) of an analyte (analyte 106) of a patient ([0037] lines 8-17, “The laboratory analyzer 102 can take an analyte 106 as an input and produce a result 108 that is a measurement of a property (e.g., height, width, volume, area, concentration, pH, or the like) of the analyte 106. The result 108 can be provided to the AoD module 104. The result 108 can include a tag that indicates the patient identity that the result 108 is associated with. The result can include a tag that indicates a time the analyte 106 was obtained from the patient.”), the analyte including one of albumin, alanine aminotransferase (ALT) ([0051] lines 1-4, “FIG. 6 illustrates, by way of example, a graph 600 of delta values vs. time for twenty-five days of measurements of an ALT analyte performed using a laboratory analyzer.”), aspartate aminotransferase (AST), bicarbonate, calcium, chloride, creatinine, phosphate (PO4), potassium, sodium, bilirubin (bili), protein composite, urea, or cholesterol;
an average of deltas (AoD) module (AoD module 104), stored on a memory and executable by the processor (Fig. 8; [0055] lines 1-9, “The storage device 816 can include a machine readable medium 822 on which is stored one or more sets of data structures or instructions 824 (e.g., software) embodying or utilized by any one or more of the techniques or functions described herein. The instructions 824 can also reside, completely or at least partially, within the main memory 804, within static memory 806, or within the hardware processor 802 during execution thereof by the device 800.”) that:
receives pairs of consecutive measurement values ([0026] lines 5-6, “A delta can be calculated (patient 1 (0 hours)−patient 1 (16 to 32 hours later)) for each data pair.”) of an analyte of the patient ([0037] lines 8-17, “The laboratory analyzer 102 can take an analyte 106 as an input and produce a result 108 that is a measurement of a property (e.g., height, width, volume, area, concentration, pH, or the like) of the analyte 106. The result 108 can be provided to the AoD module 104. The result 108 can include a tag that indicates the patient identity that the result 108 is associated with. The result can include a tag that indicates a time the analyte 106 was obtained from the patient.”), each pair of consecutive measurement values including a first measurement of an analyte obtained from the patient at a first time and a second measurement of an analyte obtained from the patient at a second time after the first time ([0066] lines 5-13, “an average of deltas (AoD) module, stored on a memory and executable by the processor, that receives pairs of consecutive measurement values of an analyte of one or more patients, each pair of consecutive measurement values including a first measurement of an analyte obtained from a patient of the one or more patient at a first time and a second measurement of an analyte obtained from the patient at a second time after the first time,”);
determines a time of day delta and a number of days delta between each pair of consecutive measurement values (Fig. 2, step 205; [0066] lines 13-15, “determines a time delta between each pair of consecutive measurement values, determines whether the time delta is within a specified time window”; [0023] “Stability in the laboratory results of hospital patients can be seen in patients that are sampled (and analyzed) only once per day, such as between 0400 and 1200 hours in many hospitals. This stability arises from at least two different independent mechanisms: 1) for many laboratory tests, there is an implicit diurnal variation, so sampling and analyzing them on a 24 hour basis will tend to cause the least variation in their sequential results; and 2) in hospitals, patient acuity of illness is associated with more frequent testing. Thus, generally, only more stable patients will be sampled about once per 24 hours. The testing can occur in the morning because of requirements for tests in the fasting status and clinicians usually perform their testing rounds in the morning and require “fresh” laboratory results to help them determine the medical course of the patient.”; [0025] “Many laboratory tests are repeated (e.g., hourly, every day, or other time frame between tests). Patients who have repeat testing at most every day (e.g., somewhere between sixteen and thirty-two hours between analyte collection) are probably quite stable and are not being aggressively treated. These patients and their corresponding measurements can provide a basis for analyzing whether an operating laboratory analyzer needs recalibration or needs to be further investigated, repaired, and/or recalibrated.”) The time delta is determined in step 205, comprises the number of days delta, which is “every day or other time frame between tests” (i.e. the number of days is 0 or 1 for every day, or otherwise for other time frames), and the time of day delta, which includes such time as “morning” or “between 0400 and 1200 hours”. One of ordinary skill in the art would recognize that the time delta taught by Cembrowski (e.g. between sixteen to thirty-two hours) includes a combination of number of days (0-1 days, wherein 1 day is 24 hours) and time of day delta (wherein the residual hours remaining after 24 hour day is factors indicate the time of day, i.e. ±8 hours from 24 hour day);
determines whether the time of day delta is within a specified time of day window and the number of days delta is within a specified number of days window, the number of days delta is an integer multiple of (Fig. 2 step 206; [0066] lines 14-15, “determines whether the time delta is within a specified time window”; [0023] “Stability in the laboratory results of hospital patients can be seen in patients that are sampled (and analyzed) only once per day, such as between 0400 and 1200 hours in many hospitals. This stability arises from at least two different independent mechanisms: 1) for many laboratory tests, there is an implicit diurnal variation, so sampling and analyzing them on a 24 hour basis will tend to cause the least variation in their sequential results; and 2) in hospitals, patient acuity of illness is associated with more frequent testing. Thus, generally, only more stable patients will be sampled about once per 24 hours. The testing can occur in the morning because of requirements for tests in the fasting status and clinicians usually perform their testing rounds in the morning and require “fresh” laboratory results to help them determine the medical course of the patient.”; [0025] “Many laboratory tests are repeated (e.g., hourly, every day, or other time frame between tests). Patients who have repeat testing at most every day (e.g., somewhere between sixteen and thirty-two hours between analyte collection) are probably quite stable and are not being aggressively treated. These patients and their corresponding measurements can provide a basis for analyzing whether an operating laboratory analyzer needs recalibration or needs to be further investigated, repaired, and/or recalibrated.”) The time delta is determined to be within a specified range at step 206, wherein the specified number of days is “every day or other time frame between tests” (i.e. the specified number of days is 0 or 1 for every day, or otherwise for other time frames), and wherein the specified time of day window is such time as “morning” or “between 0400 and 1200 hours”. One of ordinary skill in the art would recognize that the specified time window taught by Cembrowski (e.g. between sixteen to thirty-two hours) includes a combination of specified number of integer days window (0-1 days, wherein 1 day is 24 hours) and specified time of day window (wherein the residual hours remaining after 24 hour day is factors indicate the time of day, i.e. ±8 hours from 24 hour day);
determines a measurement value deltas between each pair of consecutive measurement values that includes a time of day delta within the specified time of day window and number of days delta within the number of days window ([0066] lines 15-18, “determines a measurement value deltas between each pair of consecutive measurement values that includes a time delta with the specified time window”); and
determines an AoD using the determined measurement value deltas ([0066] lines 18-19, “determines an AoD using the determined measurement value deltas”);
determines a standard deviation of a plurality of consecutive average of delta values ([0065] Example 7 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-6 to include or use, wherein determining whether the average of deltas is within a specified range of acceptable average of delta values includes comparing a standard deviation of a plurality of consecutive average of delta values to a threshold standard deviation value and the method further comprises determining the laboratory analyzer is to be calibrated in response to determining the standard deviation is greater than the threshold standard deviation.);
a compare module, executable by the processor, that compares the determined standard deviation to a range of acceptable standard deviations ([0066] lines 19-23, “a compare module, executable by the processor, to compare the determined AoD to a range of acceptable AoDs and whether a laboratory analyzer that performed the duplicate measurements needs to be re-calibrated based on the comparison.”; [0065] Example 7 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-6 to include or use, wherein determining whether the average of deltas is within a specified range of acceptable average of delta values includes comparing a standard deviation of a plurality of consecutive average of delta values to a threshold standard deviation value and the method further comprises determining the laboratory analyzer is to be calibrated in response to determining the standard deviation is greater than the threshold standard deviation.); and
an alert module that issues an alert (alert module 118) indicating the laboratory analyzer that performed the first and second measurements needs to be re-calibrated based on the comparison ([0041] lines 15-17, “The compare module 114 can provide an indicator to the alert module 118 that causes the alert module 118 to transmit a message to the proper personnel.”). The message transmitted by the alert module, resulting from the compare module determining that the AoD is not within the range of acceptable values, which includes the comparison of standard deviations, is the issuing an alert for re-calibration based on the comparison.
Cembrowski does not teach the system comprising:
a laboratory analyzer configured to obtain a first measurement of an analyte of an outpatient;
determines whether the time of day delta is within a specified time of day window and the number of days delta is within a specified number of days window, the number of days delta is an integer multiple of seven days.
Parvin teaches an analogous system (Fig. 1), comprising:
a laboratory analyzer ([0809] “Patient data: Result(s) derived from laboratory analysis of, e.g., human serum, plasma, whole blood, urine, spinal fluid, etc.: test result.”) configured to obtain a first measurement of an analyte ([0080] lines 6-8, “parameters are set for the frequency and character (e.g., number of QC test samples) of routine QC testing for each test (e.g., analyte).”) of an outpatient ([0091] “An identifier or other information uniquely identifying the instrument from which the data is preferably provided. If multiple instruments of the same type are used, they can be treated as a single instrument if they all process similar patient samples. However if one instrument is used for stat requests and another for routine requests, or if one serves outpatient testing and another serves emergency department patients, etc., then the patient results for each instrument are preferably analyzed separately.”);
determines whether the time of day delta is within a specified time of day window and the number of days delta is within a specified number of days window, the number of days delta is an integer multiple of seven days ([0024] “Time of day and day of the week are used to further characterize patient population data to calculate a z-score for use by the EWMA (or CUSUM) model.”;[0080] lines 15-23, “Another configuration step includes establishing a patient data QC protocol for each test, e.g., by truncating time-interval patient data and determining a mean and standard deviation of the remaining data population by hour of day and day of week. The QC rule (e.g., EWMA) is then optimized for accepting normalized patient data to monitor the analytical process for each test. Another configuration step includes setting parameters for confirmation testing for each test.”; [0548] “Any statistical model using patient data for analytical process control should account for the time that testing occurs (hour of the day combined with day of the week or month).”).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Cembrowski to include the measurement of analyte of an outpatient and the time deltas being an integer multiple of seven days and within a specified time of day window of Parvin because it would yield advantageous results, including calibrating laboratory analyzers based off of measurements of outpatients (who would not remain on a facility to be monitored) and across longer time deltas, thereby increasing the accuracy for calibration for timeframes on longer or different scales.
Regarding claim 10, Cembrowski in view of Parvin teaches The system of claim 9, wherein the specified time of day window includes the second measurement being within six hours of the same time of day as the first measurement (Cembrowski: [0062] “Example 4 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-3 to include or use, wherein the specified time window is between about twenty and twenty-eight hours.”). The time delta range being between 20 and 28 hours (which is ±4 hours from the 24 hour day) is within four hours of the same time of day as the first measurement.
Regarding claim 11, Cembrowski in view of Parvin teaches The system of claim 10, wherein the specified time of day window includes the second measurement being within four hours of the same time of day as the first measurement (Cembrowski: [0062] “Example 4 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-3 to include or use, wherein the specified time window is between about twenty and twenty-eight hours.”). The time delta range being between 20 and 28 hours (which is ±4 hours from the 24 hour day) is within four hours of the same time of day as the first measurement.
Regarding claim 12, Cembrowski in view of Parvin teaches The system of claim 11, wherein the specified time of day window includes the second measurement being within two hours of the same time of day as the first measurement (Cembrowski: [0063] “Example 5 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-4 to include or use, wherein the specified time window is between about twenty-two and twenty-six hours.”). The time delta range being between 22 and 26 hours (which is ±2 hours from the 24 hour day) is within four hours of the same time of day as the first measurement.
Regarding claim 13, Cembrowski in view of Parvin teaches The system of claim 8, wherein the AoD module further compares the measurement value deltas to a range of acceptable measurement value deltas and discards the measurement value delta if the measurement value delta is not within the range of acceptable measurement value deltas (Cembrowski: [0071] “Example 13 may include or use, or may optionally be combined with the subject matter of at least one of Examples 8-12 to include or use, wherein the AoD module further compares the measurement value deltas to a range of acceptable measurement value deltas and discards the measurement value delta if the measurement value delta is not within the range of acceptable measurement value deltas.”).
Regarding claim 14, Cembrowski in view of Parvin teaches The system of claim 8, further comprising an alert module (Cembrowski: alert module 118) that issues an indication that the AoD is greater than a threshold in response to the comparison module determining the AoD is greater than the threshold (Cembrowski: [0041] lines 1-6, “The compare module 114 compares the AoD 112 to one or more AoD thresholds 116. The AoD threshold 116 defines acceptable AoD values. If the compare module 114 determines that the AoD 112 is not within the range of acceptable values, an indicator signal can be provided to an alert module 118.”).
Regarding claim 15, Cembrowski teaches A machine readable storage device comprising instructions stored thereon, which when executed by the machine, cause the machine to perform operations (Fig. 8; [0055] lines 1-5, “The storage device 816 can include a machine readable medium 822 on which is stored one or more sets of data structures or instructions 824 (e.g., software) embodying or utilized by any one or more of the techniques or functions described herein.”) comprising:
operating a laboratory analyzer (laboratory analyzer 102) to obtain a first measurement ([0064] “Example 6 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-5 to include or use, wherein the consecutive measurements include a first measurement and a second measurement and the method further comprises comparing the second measurement to a range of acceptable measurement values and discarding the second measurement if the second sample is not within the range of acceptable measurement values.”) of an analyte (analyte 106) of a patient ([0037] lines 8-17, “The laboratory analyzer 102 can take an analyte 106 as an input and produce a result 108 that is a measurement of a property (e.g., height, width, volume, area, concentration, pH, or the like) of the analyte 106. The result 108 can be provided to the AoD module 104. The result 108 can include a tag that indicates the patient identity that the result 108 is associated with. The result can include a tag that indicates a time the analyte 106 was obtained from the patient.”), the analyte including one of albumin, alanine aminotransferase (ALT) ([0051] lines 1-4, “FIG. 6 illustrates, by way of example, a graph 600 of delta values vs. time for twenty-five days of measurements of an ALT analyte performed using a laboratory analyzer.”), aspartate aminotransferase (AST), bicarbonate, calcium, chloride, creatinine, phosphate (PO4), potassium, sodium, bilirubin (bili), protein composite, urea, or cholesterol;
determining a time delta between consecutive measurements, including the first measurement and a second measurement (Example 6 of [0064]; Fig. 2, step 205) of the analyte (analyte 106) made on the patient ([0037] lines 8-17, “The laboratory analyzer 102 can take an analyte 106 as an input and produce a result 108 that is a measurement of a property (e.g., height, width, volume, area, concentration, pH, or the like) of the analyte 106. The result 108 can be provided to the AoD module 104. The result 108 can include a tag that indicates the patient identity that the result 108 is associated with. The result can include a tag that indicates a time the analyte 106 was obtained from the patient.”) using the laboratory analyzer (laboratory analyzer 102);
determining whether the time delta is within an integer multiple of Fig. 2 step 206; [0025] “Many laboratory tests are repeated (e.g., hourly, every day, or other time frame between tests). Patients who have repeat testing at most every day (e.g., somewhere between sixteen and thirty-two hours between analyte collection) are probably quite stable and are not being aggressively treated. These patients and their corresponding measurements can provide a basis for analyzing whether an operating laboratory analyzer needs recalibration or needs to be further investigated, repaired, and/or recalibrated.”) and within a specified time of day window (Fig. 2 step 206; [0023] “Stability in the laboratory results of hospital patients can be seen in patients that are sampled (and analyzed) only once per day, such as between 0400 and 1200 hours in many hospitals. This stability arises from at least two different independent mechanisms: 1) for many laboratory tests, there is an implicit diurnal variation, so sampling and analyzing them on a 24 hour basis will tend to cause the least variation in their sequential results; and 2) in hospitals, patient acuity of illness is associated with more frequent testing. Thus, generally, only more stable patients will be sampled about once per 24 hours. The testing can occur in the morning because of requirements for tests in the fasting status and clinicians usually perform their testing rounds in the morning and require “fresh” laboratory results to help them determine the medical course of the patient.”). The time delta is determined to be within a specified range at step 206, wherein the specified number of days is “every day or other time frame between tests” (i.e. the specified number of days is 0 or 1 for every day, or otherwise for other time frames), and wherein the specified time of day window is such time as “morning” or “between 0400 and 1200 hours”. One of ordinary skill in the art would recognize that the specified time window taught by Cembrowski (e.g. between sixteen to thirty-two hours) includes a combination of specified number of days window (0-1 days, wherein 1 day is 24 hours) and specified time of day window (wherein the residual hours remaining after 24 hour day is factors indicate the time of day, i.e. ±8 hours from 24 hour day);
determining a measurement value delta between the first and second measurements if the time delta is the integer multiple of within the time of day window (Fig. 2, step 212; [0039] lines 10-15, “If the time delta between consecutive results for the same patient is outside of the time delta range, the filter 110 can remove the value(s) or the delta corresponding to the value(s) from the results to be used by the AoD module 104 to calculate the AoD.”);
calculating an average of deltas (AoD module 104), the average of deltas including a measurement value delta between the consecutive measurements ([0038] lines 1-5, “The AoD module 104 can determine an AoD of the results 108. The AoD module 104 can include a filter 110. The filter 110 can implement a value delta filter and/or a time delta filter that filters based on consecutive analyte results from the same patient.”). AoD is the average of deltas;
determining whether the average of deltas is within a specified range of acceptable average of delta values ([0041] lines 1-6, “The compare module 114 compares the AoD 112 to one or more AoD thresholds 116. The AoD threshold 116 defines acceptable AoD values. If the compare module 114 determines that the AoD 112 is not within the range of acceptable values, an indicator signal can be provided to an alert module 118.”);
determining whether a standard deviation of a plurality of consecutive average of delta values is greater than a threshold standard deviation value ([0065] Example 7 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-6 to include or use, wherein determining whether the average of deltas is within a specified range of acceptable average of delta values includes comparing a standard deviation of a plurality of consecutive average of delta values to a threshold standard deviation value and the method further comprises determining the laboratory analyzer is to be calibrated in response to determining the standard deviation is greater than the threshold standard deviation.);
calibrating the laboratory analyzer ([0013] lines 3-5, “Laboratory analyzers may be calibrated with calibrating solutions where the calibration can be verified by an analysis of quality control specimens.”) in response to determining the standard deviation is greater than the threshold standard deviation resulting in a calibrated laboratory analyzer ([0065] Example 7 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-6 to include or use, wherein determining whether the average of deltas is within a specified range of acceptable average of delta values includes comparing a standard deviation of a plurality of consecutive average of delta values to a threshold standard deviation value and the method further comprises determining the laboratory analyzer is to be calibrated in response to determining the standard deviation is greater than the threshold standard deviation.); and
operating the calibrated laboratory analyzer on further instances of the analyte ([0013] lines 5-16, “ If the laboratory analyzer returns the value that is expected for the control specimen within a specified tolerance, then the laboratory analyzer is considered calibrated. If not, then operation of the laboratory analyzer is investigated, possibly repaired, and may be re-calibrated so that the analyzer returns quality control results within the specified tolerance. On such systems, once the analysis of one or more quality control specimens confirms that an analytical run is accurate, the laboratorian generally assumes that the prevalence of analytically defective testing is very low.”). The laboratory analyzer, being considered calibrated such that re-calibration, investigation, and/or repair is no longer necessary for accurate results, is operated as a calibrated laboratory analyzer on further instances of the analyte.
Cembrowski does not teach the machine comprising:
operating a laboratory analyzer to obtain a first measurement of an analyte of an outpatient;
determining whether the time delta is an integer multiple of seven days and within a specified time of day window
Parvin teaches an analogous machine readable storage device comprising instructions (see description of client system 10 in paragraph [0074]) comprising:
operating a laboratory analyzer ([0809] “Patient data: Result(s) derived from laboratory analysis of, e.g., human serum, plasma, whole blood, urine, spinal fluid, etc.: test result.”) to obtain a first measurement of an analyte ([0080] lines 6-8, “parameters are set for the frequency and character (e.g., number of QC test samples) of routine QC testing for each test (e.g., analyte).”) of an outpatient ([0091] “An identifier or other information uniquely identifying the instrument from which the data is preferably provided. If multiple instruments of the same type are used, they can be treated as a single instrument if they all process similar patient samples. However if one instrument is used for stat requests and another for routine requests, or if one serves outpatient testing and another serves emergency department patients, etc., then the patient results for each instrument are preferably analyzed separately.”);
determining whether the time delta is an integer multiple of seven days and within a specified time of day window ([0024] “Time of day and day of the week are used to further characterize patient population data to calculate a z-score for use by the EWMA (or CUSUM) model.”;[0080] lines 15-23, “Another configuration step includes establishing a patient data QC protocol for each test, e.g., by truncating time-interval patient data and determining a mean and standard deviation of the remaining data population by hour of day and day of week. The QC rule (e.g., EWMA) is then optimized for accepting normalized patient data to monitor the analytical process for each test. Another configuration step includes setting parameters for confirmation testing for each test.”; [0548] “Any statistical model using patient data for analytical process control should account for the time that testing occurs (hour of the day combined with day of the week or month).”).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the instructions of Cembrowski to include the measurement of analyte of an outpatient and the time delta being an integer multiple of seven days and within a specified time of day window of Parvin because it would yield advantageous results, including calibrating laboratory analyzers based off of measurements of outpatients (who would not remain on a facility to be monitored) and across longer time deltas, thereby increasing the accuracy for calibration for timeframes on longer or different scales.
Regarding claim 17, Cembrowski in view of Parvin teaches The storage device of claim 15, wherein the specified time of day window includes the second measurement being within six hours of a same time of day as the first measurement (Cembrowski: [0062] “Example 4 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-3 to include or use, wherein the specified time window is between about twenty and twenty-eight hours.”). The time delta range being between 20 and 28 hours (which is ±4 hours from the 24 hour day) is within four hours of the same time of day as the first measurement.
Regarding claim 18, Cembrowski in view of Parvin teaches The storage device of claim 17, wherein the specified time of day window includes the second measurement being within four hours of the same time of day as the first measurement (Cembrowski: [0062] “Example 4 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-3 to include or use, wherein the specified time window is between about twenty and twenty-eight hours.”). The time delta range being between 20 and 28 hours (which is ±4 hours from the 24 hour day) is within four hours of the same time of day as the first measurement.
Regarding claim 19, Cembrowski in view of Parvin teaches The storage device of claim 18, wherein the specified time of day window includes the second measurement being within two hours of the same time of day as the first measurement (Cembrowski: [0063] “Example 5 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-4 to include or use, wherein the specified time window is between about twenty-two and twenty-six hours.”). The time delta range being between 22 and 26 hours (which is ±2 hours from the 24 hour day) is within four hours of the same time of day as the first measurement.
Regarding claim 20, Cembrowski in view of Parvin teaches The storage device of claim 15, wherein the operations further comprise comparing the second measurement to a range of acceptable measurement values and discarding the second measurement if the second measurement is not within the range of acceptable measurement values (Cembrowski: [0064] “Example 6 may include or use, or may optionally be combined with the subject matter of at least one of Examples 1-5 to include or use, wherein the consecutive measurements include a first measurement and a second measurement and the method further comprises comparing the second measurement to a range of acceptable measurement values and discarding the second measurement if the second sample is not within the range of acceptable measurement values.”).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/B.B.G./Examiner, Art Unit 2857
/Catherine T. Rastovski/Supervisory Primary Examiner, Art Unit 2863