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 potentially render large swaths of vaccine safety research not credible.

Measles Vaccination May Do 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 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.

The argument in favor of natural infection is further strengthened by four 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, promising ameliorative (or potentially curative) therapies that can likely reduce mortality and permanent morbidity – particularly intravenous vitamin C – have gone chronically ignored. Third, mathematical models predict that measles resurgence is likely inevitable, owing to a vaccine-caused derailing of the process of natural boosting which occurs in the absence of vaccines. And fourth, in the ultra long-term, measles (as well as other childhood infections) may confer many benefits that are not equivalently realized through vaccination. These potentially include prevention of cardiovascular mortality, several cancers, atopic diseases, rheumatoid arthritis, Parkinson’s disease, seizure disorders, and perhaps more.

Hence, outcomes achieved through measles vaccination may actually be inferior to implementing behaviors and treatments that emphasize amelioration of measles infection, rather than prevention. Therefore, there is no sound ethical reason to eschew the pursuit of randomized comparator trials testing measles amelioration against measles prevention. I have previously also analyzed the possibility that confounding by contraindication has led to overlooking the role that vaccines may 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 lacking.

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

Tentative Title

As written above.

Tentative Abstract

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 conceivably 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, lack of analysis of nonresponders, misleading response thresholds, and a lack of real-world outcomes. The scarce 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. As measures that can credibly address all of these flaws are entirely feasible, journal editors should commit to ceasing publication of positive trials and analyses that fail to 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, especially 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 patients may conceivably experience symptomatic improvement that is caused by antidepressants, these cases would be best explained by poorly understood nonspecific chemical effects.

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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