In Progress Research

(Posted by David AuBuchon)

I am presently working on three papers for submission to peer-reviewed journals. Below you will find the tentative titles and abstracts.

Fatal Flaws in Vaccine Safety Research: An Analysis of Confounding by Contraindication and Exposure Dilution Bias

This project is discussed in more detail on its own page, and it open to criticism. I am not presently soliciting criticism on the other two papers.

Tentative Title

As written above.

Tentative Abstract

The most important questions of vaccine safety are mostly addressed by observational studies. However, these require careful design and analysis to address many potential sources of bias and confounding. Two such sources which have received inadequate attention are confounding by contraindication (CBC) and exposure dilution bias (EDB). In studies of childhood vaccinations CBC occurs when children who have observable attributes that are associated with increased risk of adverse outcomes are simultaneously less likely to receive vaccines than are other children. This generally occurs because of parents’ perceptions that vaccines are not safe for their children with such “high-risk” attributes. Subsequently, adverse outcomes become concentrated in control groups, working to conceal any potential harms of vaccines, or even to produce spurious “protective” effects. EDB may occur when subjects in both the exposure and control groups have received other vaccines not under study that may pose identical risks. The baseline pool of those susceptible to the adverse outcome may be shrunk due to harm from other vaccines, leading to a reduction in observed harm. EDB biases any true elevation in relative risk downward towards one.

I review the literature documenting the certain or near certain existence of CBC in a variety of vaccine safety studies, with particular attention to at least 9 types of contraindications that stand to confound MMR-autism studies. I also document the likely existence of EDB in a number of contexts. I review efforts researchers have made to address these two weaknesses, sometimes successfully, and sometimes not. I document a pattern of conflicting results that suggest when CBC and/or EDB are credibly addressed, harms from vaccines are reported, and when they are not credibly addressed, an absence of those same harms or even protective effects are reported.

Fine and Chen previously derived a mathematical expression to model the effects of CBC in vaccine cohort studies. I enrich their expression to model CBC in greater detail, and to simultaneously model the combined effects of CBC and EDB. I then apply this expression to the context of MMR-autism cohort studies, demonstrating the sensitivity of reported risk ratios to both CBC and EDB. I illustrate using plausible variable values that in the event MMR and possibly other vaccines cause ASD that existing studies would very likely be incapable of detecting even a large risk.

Lastly, I offer four suggested observational study designs that reduce CBC and/or EDB. Most importantly among them is a retrospective design comparing fully vaccinated children to unvaccinated children in a manner that is ethical, probably feasible, virtually eliminates both CBC and EDB, and addresses concerns about differences in baseline characteristics between vaccinated and unvaccinated families.

I posit that CBC and EDB are the “elephants in the room” that render large swaths of vaccine safety research not credible.

Measles Vaccination Probably Does More Harm Than Good

Tentative Title

As written above.

Tentative Abstract

Measles vaccination has been proven to confer a mortality benefit, relative to contracting natural measles infection, in an acute period. In a long-term, post-acute period, both measles vaccination and measles infection apparently confer benefits to the immune system that reduce death from other infections. The overall mortality associated with vaccination in these two periods combined is thought to be superior to allowing natural measles infection. Although this is what vaccination policy is based on, the data does not convincingly prove this in general. High potential for bias and confounding in observational studies need to be more appropriately considered. Confounding by contraindication in particular is highly problematic, as high-risk children tend to become concentrated in control groups. Even a single such unaddressed source of confounding could lead to a high degree of overestimating the merits of vaccination, and underestimating the merits of allowing natural infection. And indeed, there is a likely source of confounding by contraindication which has never been considered. Recent studies highly suggest that DTP vaccine has harmed and killed more children than it has saved historically. Since virtually all studies of measles vaccine that have suggested benefit have been done with children who have received DTP months earlier, observable adverse reactions to DTP should be expected to cause children at high-risk of death to avoid measles vaccine, thus confounding results. This interpretation is consistent with the facts that DTP appears to kill more girls than boys, while measles vaccine appears to save more girls than boys. It is also consistent with the fact that those who receive measles vaccine with DTP either simultaneously or after have higher mortality than those who receive measles vaccine with DTP given prior.

The argument in favor of natural infection is further strengthened by eight more factors. First, in the absence of vaccination, incidence and severity of the more lethal secondary cases of measles infection can be significantly reduced through behavioral changes. Second, in the absence of vaccination, behavioral changes can concentrate measles cases in the optimal range of 5 to 8 years of age, where infection poses exceptionally low risk. Third, other socioeconomic factors that may explain as high as a 10-fold disparity in mortality can also be addressed. Fourth, promising ameliorative (or potentially curative) therapies that can likely reduce mortality and permanent morbidity – particularly intravenous vitamin C – have gone chronically ignored. Fifth, mathematical models predict that measles resurgence is likely inevitable, owing to a vaccine-caused derailing of natural boosting which occurred in the absence of vaccines. Such resurgence shifts infection towards an adult population where measles poses several-fold higher risk of death than infection in childhood. Unborn children of infected mothers have an especially high death rate. Sixth, historical underreporting of mild measles cases has led to perhaps a 10-fold exaggeration in measles death-to-case ratio. Seventh, it must not be forgotten that measles-containing vaccines are not free of harm, and create what is consistent with mild versions of viral illness. In one setting, vaccinations given at 12 months (which included MMR) were associated with an additional 1 in 168 children experiencing emergency room visits or hospitalization. Eighth, in the ultra long-term, measles (as well as other vaccine-preventable infections) may confer many benefits that are not equivalently realized through vaccination. These potentially include reduced prevalence and/or mortality from cardiovascular disease, several cancers, atopic diseases, rheumatoid arthritis, Parkinson’s disease, seizure disorders, and more.

Hence, for all the reasons described, outcomes achieved through measles vaccination are probably inferior to implementing behaviors, treatments, and socioeconomic changes that emphasize amelioration of measles infection, rather than prevention. It is within the realm of possibilities that death due to measles can be reduced to virtually zero without vaccinations, while still maintaining the benefits of allowing natural infection. Therefore, there is no sound ethical reason to eschew the pursuit of randomized comparator trials testing measles amelioration against measles vaccination. I have previously also reported on the reality that confounding by contraindication has likely led to overlooking the role that vaccines play in the pathogenesis of chronic conditions, including measles-containing vaccines. As this becomes more fully realized, the climate against randomized vaccine study designs should be further softened. Targeting measles for eradication would be a decision that requires a very high level of evidence that appropriately establishes ultra-long term superiority to an ameliorative approach. The required evidence to indicate this is starkly lacking.

Antidepressants Must Be Abandoned: A Review of Bad Science and Wishful Thinking

Tentative Title

As written above.

Tentative Abstract

[presently being reworked. Check back later].

Antidepressants lack any credible evidence-based indication. Long-term studies that control for comorbid conditions and premedication depression strongly suggest that antidepressants cause both death and worsening of depression. This is consistent with the fact that antidepressants are associated with more than 50 types of adverse events, many of which are life-shortening. Positive interpretations of short-term randomized controlled trials fail to address numerous systematic sources of bias and confounding, all of which serve to overestimate efficacy and underestimate harm. These include multifaceted reporting biases, unblinding bias, cold turkey design, short trial durations that censor spontaneous remissions, multifaceted sponsorship biases, and lack of analysis of nonresponders, misleading response thresholds,

 

and a lack of real-world outcomes. [ this doesn’t necessarily understimate efficacy]

 

Attempts that have been made to describe these weaknesses as unimportant have failed to impress. Antidepressants almost certainly do not work, and it is a very tenable hypothesis that they rather worsen depression, even in the short-term. Thorough and longstanding documentation of the described flaws has not led to better-designed trials and analyses. The roles of both fraud and wishful thinking in these happenings should not be underestimated.

The benefit-risk trade-off of antidepressants is further troubled by rampant overdiagnosis of depression, which results in numerous direct drug harms, as well as harmful nocebo effects. These harms are not reflected in analyses of trials. Clinical trials also generally exclude an estimated 82% of “real-world” patients. Evidence suggests that trial participants have higher rates of response and remission than does a general population, making the generalizability of antidepressants unfounded.

[zimmerman suggests the above stacking is intentional. so place this next to the other 10 flaws. So maybe that makes 11 or 12. what measure can address numbers 11 and 12?]

I propose 10 measures that can credibly address all of these flaws, and that these measures should be adopted as the definition of a high-quality antidepressant trial. As all of these measures are feasible, journal editors should strongly favor the publication of trials and analyses that follow them. Unless and until such high-quality trials indicate the efficacy of antidepressants, the ethical and evidence-based course of action is for physicians to abandon all new prescriptions of antidepressant drugs, most urgently in the elderly. The view that individual antidepressants need to be debated specifically is based on a false balance. Faulted clinical trials, a lack of any reliably documented neurotransmitter deficiency, several other logical flaws with the monoamine hypothesis, and the similarity in short-term effects between antidepressants other classes of drugs do not support the existence of a specific antidepressant drug effect. While some unpredictable patients may conceivably experience short-term symptomatic improvement that is caused by antidepressants, these cases would be best explained by poorly understood nonspecific chemical effects.

As they stand, antidepressants do not have a valid place in the treatment of depression and should be abandoned.

Mention evironmental complexity, natural treatment options, and biological victim consciousness in the abstract as well]

[in the manuscript, add 84% long-term treatment to the overdiagnosis segment. Also make a note that the “subjectivity” references should be moved to hte overdiagnosis section, as these all collectively show physicians cannot responsibly prescribe.]

Support These Research Projects

I’ve been quietly working on these projects for a long time, without pay. Make a donation if you wish to show your support. An increasing number of reputable journals are offering authors a choice between subscription-based access and open access. I will opt for open access, in which case the author(s) are expected to cover the fees of publication. This can range from $1000 to $5000 per accepted manuscript.

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