Our testing protocols are designed to generate data suitable for submission to the US Food and Drug Administration needed for device approval.
We are approved by the UCSF Committee on Human Research for desaturation testing to SaO2 levels as low as 50% on healthy non-smoking volunteers; however standard testing is to a minimum of 70% SaO2 is typical.
Testing is done at stable steady state levels of inspired oxygen to achieve target saturations evenly distributed between 70 and 100%. To achieve steady state levels of saturation, continuous airway gas analysis by mass spectrometer and computer is utilized. Pulse oximeter readings are compared to multiwavelength oximetry (Radiometer OSM-3 Hemeoximeter). A typical test involves 12 saturation plateaus, with a total of 24 arterial blood samples for each subject. Six subjects can be studied in one day, 12 subjects over 2 days. Variations on this theme include simultaneous testing of different probe types and body locations, testing of remanufactured probes, testing of probes in selected subject populations (skin pigment, gender), etc.
Motion fixtures to simulate patient motion can be incorporated into the testing (provided by manufacturer.)
Low perfusion conditions can be created by external clamps, cuffs, etc. Arterial blood pressure monitoring can be done as well. Different body positions are also possible (e.g. Trendelenburg) during testing.
This laboratory has developed methods that permit us to test multiple pulse oximeters simultaneously. We induce sudden profound and brief stable arterial oxygen desaturation in normal, paid volunteers and sample arterial blood when a stable level of hypoxia has been attained for analysis in a gold standard bench CO-oximeter. This section describes the program, arrangements, and costs. 6 to 8 subjects can be studied in a single day, with 20-25 arterial blood samples from each subject. 10 to 12 subjects can be studied over two days, with 20-25 arterial blood samples each.
The key to this is a computer program that permits the inspired gas mixture to be adjusted by an operator who observes a breath-by-breath display of the arterial saturation computed from end tidal PO2 and PCO2, which is continuously monitored by mass spectrometry. Typically, saturation is determined once with air breathing and then reduced suddenly to one of 6 levels, range as requested, e.g. 94%, 90%, 85%, 80%, 75% and 70%, for about 30-60 seconds at each level. An arterial blood sample is obtained from an indwelling catheter at the end of each hypoxic plateau. The operator changes the inspired oxygen concentration at the end of each blood sampling and the sudden change this produces in the oximeter recording is used as a time marker for subsequent analysis.
A "run" takes 5-7 minutes, during which several plateaus are obtained, e.g. 90%, 80%, and 70%; the run is terminated by a breath of 100% O2 followed by room air. Two runs together compose the six levels of saturation previously mentioned. Saturation of each arterial blood sample is determined by direct oximetry in a Radiometer OSM-3 multi-wavelength oximeter.
Normally, each tested oximeter should provide an electrical analog output signal that we record with LabVIEW in the computer for subsequent plotting and statistical analysis. The timing of the arterial sample on the pulse oximeter recording is obtained from the record of that oximeter using the abrupt fall to a lower plateau or rise produced by re-oxygenation. The mean oximeter output between 6 and 12 seconds before the sudden change of SpO2 is recorded and is read by cursor on a color terminal, and the value transferred to a file for statistical analysis in Excel. The output files include data collected at 2 Hz for each oximeter, and are available on CD or other media, for analysis. A study normally consists of one normoxic and 19-24 hypoxic comparisons for each subject.
In many modern pulse oximeters no analog output is provided. If the manufacturer chooses to record the data in a portable computer at a rate of at least 1 Hz, that data can also be submitted to us for data analysis without extra charge. If we are not asked to analyze data, the charge will be as shown for the first 4 instruments, with additional oximeters counted as non-recorded instruments in the following table.
If a manufacturer prefers to collect and analyze the data, the continuous digital signal of each oximeter should be read, for comparison with the blood sample, 9 seconds before the record shows a sudden fall or rise in oxygen saturation, not at the time of blood sampling. This procedure accounts for the delays of finger circulation and uses the estimated delay from the lung to the sample site. There is no useful correlation between the actual time of blood sampling and the oximeter recording because of the extreme variability of tissue blood flow lag.
These studies are done with approval of the UCSF Committee on Human Research (H1094-01706-21, exp. date April 6th, 2007). The study takes about 1 hour of each subject's time. Reduction of the data requires several days. Manufacturer’s representatives may be present for these tests, and may mount the probes. An extra charge is made if no representative is present, requiring us to mount the probes.
In all cases, the blood analysis data are provided, including the SaO2, MetHb, COHb and Hgb concentration.
The data analysis report will consist of the following:
Technically, we can record data if each oximeter control unit provides a single ended analog output signal with BNC terminal mounted on the box. We provide cables to connect this to our computer. The oximeter probe leads should be at least 8 ft long. If no analog outputs are supplied, the manufacturer will be responsible for data recording.
Manufacturers must provide their own pulse oximeters and probes. Each individual manufacturer is charged an amount determined by the number of subjects, the number of samples per subject, and the number of oximeters (as shown by the cost table on the next page) plus the facility fee and UCSF overheads. Sites may include the fingers, ears, forehead and bridge of the nose. Data are not published without specific permission of the manufacturer, and in general, no plans now exist for publication of future data.
Usually, the US FDA requires that at least 200 data points from in vivo accuracy testing are included in an application for device approval. The FDA has specified that 200 data points are necessary for each oximeter and probe type combination. Of course, multiple combinations of probes and oximeters can be studied simultaneously on each subject. Probes on any body area have been studied in our laboratory including ears, bridge of nose, forehead, back, chest, and toes. We do not recommend placing probes on the thumb.
For the approval of neonatal pulse oximeters, the FDA may also require data from neonates/infants obtained in the clinic or hospital. Desaturation testing of neonatal probes is done in adults (we recommend smaller fingers). Clinical data for pulse oximetry accuracy can be obtained at UCSF in neonates who require cardiac surgery, in a protocol under the direction of Dr. Greg Stratmann. Contact Dr. Bickler for more information.
The FDA has also stated that testing in human subjects must include individuals of both genders and of a range of skin pigmentation.
We believe this information to be accurate, but cannot make guarantees concerning the details of current FDA guidelines. The manufacturer is responsible for determining what FDA requirements are applicable to the devices they are testing.
Manufacturers are encouraged to arrive in San Francisco the day before testing to set up equipment and make sure that data acquisition systems are working properly.
The manufacturer is charged an amount determined by the number of subjects, the number of blood samples per subject, and the number of oximeters (as shown by the cost table on the next page) plus the facility fee and UCSF overheads.
The costs of performing the study, paying the subjects, developing the computer facility and program, plotting the individual responses, and of personnel salaries require that we obtain payment for these studies as shown on the accompanying table. These tests are also used to support the physiology research of this laboratory.
No extra charge is made for dual recording of oximeters by both manufacturers and us. If the manufacturer chooses not to be present for the tests, an additional 10% charge will be added. If two manufacturers both agree to share a study date, 15% will be taken off the charge to each manufacturer.
We charge a 7% fee to maintain the equipment in the testing facility. Also, UCSF adds an additional 22% overhead charge to the amounts computed from the following table. A 50% cancellation charge is applied to studies cancelled within 1 week of the study date. A contract for each study must be in place prior to the start of the study. In some instances, particularly with new companies or companies from overseas locations, we may require a partial payment for the study in advance. The costs are determined as the sum of the following: #subjectsX$550 + #blood samples X$180+#recorded oximetersX$350+#unrecorded oximeters X$200. To this are added the department fee and University overhead as shown in the following table.
Example: A manufacturer wishes to do a study with 10 subjects, with 22 samples from each subject. The manufacturer has 6 oximeters that he wishes us to record and analyze and 2 additional oximeters that he does not wish us to record. The total charge of $16,124 for this scenario is computed as detailed below:
Sponsor: |
Beautiful Pulse Oximeters, Ltd. |
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Period: |
11/20/08-12/19/08 (Study dates: 11/20 & 11/21) |
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Title: |
Accuracy of pulse oximeters with profound hypoxia |
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Study No. |
PHYS01 |
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All amounts are in US Dollars |
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5,500 |
10 |
subjects |
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3,960 |
22 |
samples |
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2,100 |
6 |
oximeters, recorded, or unrecorded ≤4 |
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400 |
2 |
oximeters, unrecorded >4 |
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11,960 |
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Subtotal |
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837 |
7% |
Anesthesia Department Fee |
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12,797 |
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Subtotal |
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3,327 |
26% |
UCSF Indirect Costs |
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16,124 |
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TOTAL COSTS |
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If creation of carboxyhemoglobin or methemoglobin is involved in the study, the costs will be increased by 30%. For such studies, we can study 6-8 subjects over 2 days. If control of arterial CO2 to particular targets is required (e.g. for testing of transcutaneous CO2 monitors) , costs will increase by 15%. Costs are also increased by 15% if studies involve low perfusion, for example to a target arterial blood pressure or pulse volume index. Reductions in blood pressure in the radial artery of about 30% are possible by using a device to compress the brachial artery.
If a special volunteer subject population is requested for study (i.e. all very darkly pigmented subjects), costs will also increase by 15%. There is no additional charge for testing under motion conditions, but the manufacturer must supply any motion-creating equipment for the tests.
We have the ability to record directly from pulse oximeters to computer with LabVIEW (National Instruments) using analog or serial connections.
For analog output, we can record up to 14 devices. Our inputs require BNC connectors, so adapters will likely be necessary. We will need information on the type of connector used. We assume 0-1 or 0-10 volts for a saturation range of 0-100%. If devices are different, we will need to know ahead of time, but can probably accept any voltages.
For serial device, we use standard RS-232 connectors and can record up to 16 devices. We expect the oximeter to have a female connector. If the connectors are different, we will need to arrange for adapters.
Because different oximeters send different ASCII data, we will need to have the oximeters in advance to be able to properly translate any serial data. We will also need information on the serial connection protocol, including baud rate, and the number of data bits.
ABL 800 FLEX
Ideal for medium- to high-volume testing, the ABL800 FLEX measures any combination of pH, blood gas, electrolyte, oximetry and metabolite parameters. This highly accurate analyzer offers many automated features to help streamline work processes and reduce errors.
OSM 3
The OSM 3 is used in our pulse oximeter testing. This machine is ideal for processing samples quickly and accurately, which is necessary for handling the high volume of samples in a pulse oximeter study.
LabView
We have the ability to record directly from pulse oximeters to computer with LabVIEW (National Instruments) using 16 analog or 16 serial connections.
Board certified anesthesiologists are present continuously during all testing. Arterial lines, intravenous lines and all monitoring is done by these physicians. We have a perfect safety record during 24 years of studies with more than 3000 subjects participating.
