Assumptions are where art meets science, and, these days, the scientific literature is beginning to look like a Jackson Pollock drip-painting. Those that keep up-to-date on the pandemic literature have undoubtedly encountered the test-negative case-control design (TND). Famously, the Center for Disease Control used a TND to declare that
In a normal world, there is no such thing as asymptomatic infected ~ only pre-symptomatic and symptomatic infected. In a normal world, you would not test just anyone, you would only test the symptomatic. In addition to "over-testing", we use testing techniques, PCR and antigen, that can produce false positives and false negatives. The PCR is especially useful because you can virtually guarantee a positive result by using a high number of cycles. It just seems to me that we have testing scenarios set up for the express purpose of producing high case numbers, while making it virtually impossible to determine VE. Based on your expose of TND, I now know that the scientific community has created another method of biasing already biased/corrupted data.
Thank you! I'm glad to learn how to be wary of this kind of design. And, I especially liked your first sentence, "Assumptions are where art meets science, and, these days, the scientific literature is beginning to look like a Jackson Pollock drip-painting."
The masked maniacs are lining up to get tested because they’re jonesing on the dopamine hits that come from participating in a global fear porn operation.
I’m still waiting for Covidiots to start using fabric condoms to prevent transmission of HIV. If a fabric mask will stop Covid, why wouldn’t a blue cloth stop HIV?
Thank you for the great write-up. I'm in agreement with you about healthcare seeking behavior being normalized is a tenuous assumption but I was under the impression that this design is better at tracking asymptomatic Infections which from a VE standpoint is absolutely essential to stop transmission. I tended to think that TNDs did better at showing this risk due to better incidental coverage of infections [say getting on a plane or entering a hospital to meet a patient].
I agree that hypochondriacs will affect symptomatic VE as will government or structural biases that differentially allow people access or inaccess but I still think those could be mitigated somewhat. For example we can take the first or the last positive or negative test and discard the rest. One advantage that I've mentioned to you before of TNDs in my view is seeing the sensitivity of the outcomes to inclusion criteria where a person was initially a case then later becomes a control or vice versa. Real life has people who test positive then negative then vaccinate then positive again etc. This is an interesting case pathway because it has hidden risk that regular observational cohorts studies miss due to matching and following and not allowing switch over.
I think one other really big weakness of TNDs is the lack of any basis to control what the investigator decided is a matched pair and discarded the other. I will once again mention that I couldn't believe my eyes that a Qatar preprint that showed severe cases in first two weeks after vaccination magically had no difference in VE by the time it was printed in NEJM. The raw data shows the investigator clearly had an anomalous string of fortuitous matches that accrued to save the VE in 1 month that was not happening for so long. Seems suspect.
Thanks for this fine write-up I did not realize test-taking was being used as an instrumental variable in this way but I agree it is a highly suspect assumption.
In a normal world, there is no such thing as asymptomatic infected ~ only pre-symptomatic and symptomatic infected. In a normal world, you would not test just anyone, you would only test the symptomatic. In addition to "over-testing", we use testing techniques, PCR and antigen, that can produce false positives and false negatives. The PCR is especially useful because you can virtually guarantee a positive result by using a high number of cycles. It just seems to me that we have testing scenarios set up for the express purpose of producing high case numbers, while making it virtually impossible to determine VE. Based on your expose of TND, I now know that the scientific community has created another method of biasing already biased/corrupted data.
Thank you! I'm glad to learn how to be wary of this kind of design. And, I especially liked your first sentence, "Assumptions are where art meets science, and, these days, the scientific literature is beginning to look like a Jackson Pollock drip-painting."
Thank you for this clear explanation of test-negative design.
The masked maniacs are lining up to get tested because they’re jonesing on the dopamine hits that come from participating in a global fear porn operation.
I’m still waiting for Covidiots to start using fabric condoms to prevent transmission of HIV. If a fabric mask will stop Covid, why wouldn’t a blue cloth stop HIV?
Thank you for the great write-up. I'm in agreement with you about healthcare seeking behavior being normalized is a tenuous assumption but I was under the impression that this design is better at tracking asymptomatic Infections which from a VE standpoint is absolutely essential to stop transmission. I tended to think that TNDs did better at showing this risk due to better incidental coverage of infections [say getting on a plane or entering a hospital to meet a patient].
I agree that hypochondriacs will affect symptomatic VE as will government or structural biases that differentially allow people access or inaccess but I still think those could be mitigated somewhat. For example we can take the first or the last positive or negative test and discard the rest. One advantage that I've mentioned to you before of TNDs in my view is seeing the sensitivity of the outcomes to inclusion criteria where a person was initially a case then later becomes a control or vice versa. Real life has people who test positive then negative then vaccinate then positive again etc. This is an interesting case pathway because it has hidden risk that regular observational cohorts studies miss due to matching and following and not allowing switch over.
I think one other really big weakness of TNDs is the lack of any basis to control what the investigator decided is a matched pair and discarded the other. I will once again mention that I couldn't believe my eyes that a Qatar preprint that showed severe cases in first two weeks after vaccination magically had no difference in VE by the time it was printed in NEJM. The raw data shows the investigator clearly had an anomalous string of fortuitous matches that accrued to save the VE in 1 month that was not happening for so long. Seems suspect.
Thanks for this fine write-up I did not realize test-taking was being used as an instrumental variable in this way but I agree it is a highly suspect assumption.