PSA doubling time or PSADT is a valuable prognostic factor in assessing the need for second- or even third-line treatment in men with biochemical progression of prostate cancer.
However, one of the major problems in the use of PSADT is the fact that there is no “standard” method for calculating this factor — and different methods for computing PSADT can lead to inconsistent results, above and beyond the inevitable variability of the basic PSA data.
Ponholzer et al. set out to develop a standardized, reproducible method for PSADT determination which could also offer a mechanism to estimate PSADT error. Better still, they have made this PSADT calculator available on line, complete with graphic output.
If you want to use this calculator to assess your PSADT with accuracy,
- You need to know your last three PSA test results and the exact dates the blood samples were taken; the tests should all have been conducted at the same laboratory and using the same assay.
- There should be a period of at least 3 months between the first and the last PSA test.
- You should have had no medical treatment between the first and the third PSA tests.
- You should be sure you have had no infection, no prostate manipulation, and no problems with urinary retention during the time period.
- You should not subtract the nadir level from your PSA; use the actual PSA levels.
American readers should be careful to note that dates should be entered into the calculator using the European format of day, month, year (e.g., 23.05.2010) and not the American format of month, day, year (e.g., 05.23.2010).
The authors are careful to point out that their tool is not any “better” than other tools that are available, but it is based on a standardized “least squares” error methodology, and it is available for anyone to use for free!
Filed under: Living with Prostate Cancer, Management | Tagged: calculator, on-line, PSA doubling time, PSADT |
THE "NEW" PROSTATE CANCER INFOLINK 
It appears from recent letters from the FDA described above in sitemaster’s article on “genetic testing in the real world” that calculators such as PSADT are considered by the FDA to be “medical devices” that require FDA approval. Misinformed American’s, for example, might enter dates using our system instead of the European with the same devastating results described for genetic testing.
It’s an interesting question, but I don’t believe the FDA is empowered to regulate a computational tool that is freely available and which is based on clinical data.
Section 201(h)(2) of the FDCA defines “device” as: “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is…intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals”
In its letter to Knome, the FDA declared that a software program which aids in diagnosis of a condition is a device:
“During a meeting between Knome and FDA on August 6, 2009, you described KnomeCOMPLETE™ as consisting of a software program that analyzes genetic test results that are generated by an external laboratory in order to generate a patient-specific test report. Thus, the KnomeCOMPLETE™ is a diagnostic device and subject to all applicable requirements of the Act.”
Obviously [a] PSADT [calculator] is a software program used in the diagnosis of a condition too. Hence it is a FDA-regulated device subject to all its requirements. Those listed requirements do not exempt regulated devices provided free, or based on 5,500 “clinical trials”.
Even if you access PSADT via your cell phone web browser, you would be making it part of an FDA device that would need approval and submission of an application with analytical and clinical validity for each cell phone identified by serial number to use it and all included software that might interface with PSADT in the process.
Perhaps if you let your doctor use your cell phone to access and input data and interpret the results for you and determine what part of the information produced should be communicated to you; it might be ok; but probably not. It would probably take half an hour and cost you $500 for medical service after making an appointment for a month in advance. Your doctor might just say this PSADT has no proven “clinical use” or that the cell phone is not an approved medical device for this purpose so it can’t be used clinically.
Tasker:
So if you are correct (which I don’t know, because I am not an expert on the interpretation of the FDCA), you will need to explain to me why the FDA has not — at any time in the past decade or so — made any comment on the theoretical need you suggest to regulate access to: the Partin tables, the Han tables, the Kattan nomograms, and about another 200 or so prognostic tools of greater or lesser value (referring soley to prostate cancer). I’m fine with your apparent view that the FDA is inconsistent in its actions, but my suspicion is that that has more to do with the marketing of things that make money based on a lack of transparent data than with access to data published in the scientific literature (which the FDA has never sought to regulate).
The excercise of deferred enforcement is not (as some might characterize it) inconsistency but merely risk-based administrative discretion. Whether an enforcement position ought to be taken with respect to a medical device may depend on how its is marketed. Also some things are grandfathered.
A publicized medical device that is dangerous because it gives inconsistent diagnosis leading to improper self-treatment might be suspected of being risky, provoking an examination of whether continued deferred enforcement is appropriate. For example, some people might just plot PSA against time and estimate the slope of the line by eyeball. Others might consider it more appropriate to use log(PSA) against time. For various reasons, other approaches have been taken, too. There are a number of curve-fitting programs which can produce different results for valid reasons. Someone could use a non-transparent software program to attempt to calculate a doubling time. If, by inadvertance, the data input was not properly checked by validation routines, someone could be misled to believe his doubling time was very low and defer getting prostate treatment. Or, perhaps, the user was also taking a hair loss prevention drug that the software did not warn about as a contraindication. One could think of a large number of questions about software.
Overall, whether enforcement of the code in a particular situation is warranted could be a very complicated question possibly resulting even in litigation. This is probably why discretion is vested in the agency, which has suggested that it may adopt a risk evaluation standard of some kind and has sought public input on it.
All in all for anyone it is a daunting activity to attempt to understand the nuances of FDCA. Clearly there is ample room for disagreement about many features of FDAC by reasonable people. Consequently, many are looking at the Knome FDA Letter for insight into this new activity with respect to a product that has been on the market for a reasonable period of time. Even Congress may act to provide new direction.
Family history data may seem very simple versus similiar data from DNA. The issue seems to concern whether modern techniques are more error prone or less transparently documented. Yet, there has to be some reasonable basis that will allow agreement on what is going to be accepted to allow progress in improving health care. Perhaps a NIH-curated SNP database would be considered similiar to journal-published data in the realm of transparency, but what if there were multiple databases making different assertions about SNPs?