[Paracelsus]

(09-03-2018 06:37 PM)Roosh Wrote:  

The HPV vaccine may not be as safe as people think. A new study showed that women who take it have less fertility. In other words, the vaccine may have a sterilizing effect.

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Birth rates in the United States have recently fallen. Birth rates per 1000 females aged 25–29 fell from 118 in 2007 to 105 in 2015. One factor may involve the vaccination against the human papillomavirus (HPV). Shortly after the vaccine was licensed, several reports of recipients experiencing primary ovarian failure emerged. This study analyzed information gathered in National Health and Nutrition Examination Survey, which represented 8 million 25-to-29-year-old women residing in the United States between 2007 and 2014. Approximately 60% of women who did not receive the HPV vaccine had been pregnant at least once, whereas only 35% of women who were exposed to the vaccine had conceived.

https://www.tandfonline.com/doi/abs/10.1...de=uteh20&

Has anyone got a link to the actual study rather than the abstract, and are there any statisticians or probability-minded folks here who can analyse the data?

The website indicates they used logistic regression to somehow winnow out other causes, but doesn't speak to how. So, in the interests of looking into this stuff, I went looking to see who the author was: Gayle DeLong. And the reason I did that is because DeLong is an author of a 2011 article on that same website saying that there's an association between vaccines and autism.

And it takes one Google Search into DeLong's credentials to see there's some problems with the authorship. For a start, she's not a medical researcher, and not a scientist.

She is, in fact, an economist from Baruch College, which funded the study. As in, that brand of people that Nassim Taleb regularly indicates have zero idea of how probability or the real world actually operates. So, strike one.

As for the study itself? Well, as said, we haven't got it to hand, but there seems to be a website that did critique the study -- this one:

https://respectfulinsolence.com/2018/06/...le-delong/

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Here’s what she did. She used two databases. The first was the Natality Information section of the CDC Wide-ranging OnLine Data for Epidemiologic Research (WONDER) database recording live births. There didn’t seem to me to be much point to this because all Delong did with it was to show that there was a sharp decline in the US birthrate beginning in 2007 associated with the economic meltdown that hasn’t recovered yet. As they say on Game of Thrones, it is (already) known.

Next, Delong used responses to the National Health and Nutrition Examination Survey (NHANES). This is a survey that collects data on health status of individuals in the United States along with demographic and socioeconomic information. The National Center for Health Statistic (NCHS) at the CDC administers the survey and selected a representative sample of the US population based upon complex sampling procedure. Delong notes that in 1999 NHANES asked females aged 12 and up whether they’ve ever been pregnant (or are pregnant now) and, if so, how many live births, miscarriages, stillbirths, tubal pregnancies, and abortions they’ve had. Then, starting in 2007, the survey started asking females aged 9 or above whether they’ve had an HPV vaccine. Delong then justifies the age range selected thusly:

Quote:

In 2015, the NCHS moved these questions to the National Health Interview Survey, an annual survey that is not directly compatible with NHANES. The years of study are therefore 2007—when NHANES first asked about HPV vaccine uptake—to 2014, the final year NHANES included the questions concerning pregnancy and HPV shots.

Of course, that makes me suspicious right there. These are CDC-administered surveys and the databases are maintained by the CDC. The NHANES and NHIS datasets can both be accessed through the CDC website. Moreover, if the same basic survey questions were simply moved from one survey to the other, there’s little reason why Delong couldn’t have accessed later data.

Be that as it may, Delong used the dataset as described above. The study thus used various analyses to determine whether the odds of having been pregnant (the response variable) were influenced by explanatory variables such as receiving the HPV vaccine. What she found was this. Approximately 61% of women who had never received the HPV vaccine had become pregnant at least once, whereas only 35% of those who were exposed to the vaccine did. Among married women, 77% of women who had not received the vaccine had conceived, while only 51% of those who had received the vaccine had become pregnant. She then estimates that if 100% of females in the study had received the HPV vaccine there would have been 2 million fewer pregnancies. Among never-married women 44% of those who did not receive the HPV vaccine had been pregnant, while 28% of those who had received it had conceived. By univariate analyses, the results for all women and married women were statistically significant. However, when covariates (factors that could be confounders) were included in the model and logistic regression carried out, the results for never-married were no longer statistically significant.

Where it really gets interesting is the logistic regression including covariates in which the number of HPV shots received (one, two, or three) was related to the likelihood of getting pregnant. In this model, almost none of the comparisons were statistically significant. The only two where there was a statistically significant result were for the full sample, one shot versus no shots and three shots versus no shots. To me this is a huge red flag that the results are not robust and that there is no dose-response observed. If HPV vaccination was truly causative for infertility, there should be a dose-response curve. The effect seen should be bigger and more robust across more groups as the number of HPV vaccines received increases. It’s not.

There’s also another huge problem with this study. One of the most important covariates that could impact pregnancy rates is (obviously) usage of contraception. Yet nowhere in the analysis is there a consideration of contraception usage. Yes, Delong brings up the lack of statistical significance of the results among never-married women by suggesting that maybe most of them want to avoid pregnancy (which could be true), but, again, contraceptive use is an incredibly important factor, which was not even included as a covariate. My first thought was that maybe it was a question that wasn’t asked. It’s possible. Oh, wait. It’s not. The questionnaire asks whether a female has ever used oral contraceptives, if she is taking them now, and how long she’s taken them. So why did Delong not include oral contraceptive use in her analysis? She could have. She doesn’t even really discuss it other than discussion of contraceptive failure rates. I strongly suspect there was a reason for this. I also strongly suspect that a correlation between HPV uptake and oral contraceptive use (which is not unreasonable to hypothesize) could explain the results Delong observed and that correcting for oral contraceptive use in the survey sample would likely have resulted in the results of the logistic regression no longer being statistically significant. In fairness, if the correlation is not positive but negative (i.e., HPV vaccination is associated with less oral contraceptive use), the results could be more robust than what Gayle found.

In any case, I can see only two explanations for Gayle Delong’s not having done this analysis, given that the data appear to have been available. Either she was clueless and didn’t even consider it as a covariate, or she did some exploratory analyses and with contraceptive use included the effects that she saw disappeared. After all, they weren’t very robust; so I suspect that it wouldn’t take much. I welcome comments from the epidemiologists who read this blog. After all, existing evidence largely contradicts Delong’s findings, with HPV vaccination having no effect on fertility except in one group. The group? In females with a history of sexually transmitted infections or pelvic inflammatory disease (i.e. a group at high risk of exposure to HPV infection), HPV vaccination made pregnancy more likely.

In the end, though, regardless of whether the inclusion of oral contraceptive use as a covariate would have affected the analysis, what we have here is another example of amateur hour. Gayle Delong did the analysis basically by herself with the help of an incompetent (David Geier), another economist (Sabastiano Manzano), and a professor of history who is her husband (Jonathan Rose). Having read a number of epidemiology papers and co-authored a couple (with, I hasten to add, actual epidemiologists, population scientists, and statisticians), I got the distinct feeling reading Delong’s paper that she didn’t know what she was doing.

Analyse the rest of the discussion for yourself, but even on DeLong's abstract that was the first question that occurred to me as well: how did DeLong control for the fact this age group, 25-29, is likely on contraceptives? How did she eliminate that as a cause for the massive dropoff in fertility in that age group? How did she control for the fact that first baby age is heading for the thirties anyway in the West?

Now, I fully anticipate that from this point, the thread will likely regress into the usual shitshow of circular and bootstrap-levitation logic that seems to apply in a lot of anti-vaccination debates, so let me say this in anticipation -- the HPV vaccine might warrant some caution first on what I'd call the Talebian Test: it's a vaccine that's only 10 years old, and time is the ultimate test of whether something is a good idea or not. Most vaccines -- the oldest ones, that is -- tend to be proven as safe mainly because you have a vast array of time samples to draw from, but the HPV vaccine hasn't quite got that age on it as yet. Still, if this critique of that article is right, I wouldn't be relying on DeLong's analysis as a foundation for saying the HPV vaccine is an infertility drug.