Federal Protocols Offer Many Opportunities To Bias Science

This article is one in a series. For the other articles, please see:  INDEX: “Why You Can’t Trust Government Science”


 

This article is continued from: Old Ideas, Old Science Cripple Federal Regulation


Rigid Lab Protocols Encourage Under-Reporting Of Adverse Effects

The Boston University study notes that,

“The main means of controlling the quality of private research and protecting against biases in study design and reporting is through the specification of testing protocols.

“These protocols set forth cookbook-like requirements for conducting specific types of toxicity and related studies.

“If the protocols do not specify precise categories of adverse effects (or endpoints) for animals exposed to toxins, then there is remaining discretion in what to count as an adverse effect or what unexpected effects to notice and report.Some of the tests can also be altered or designed in ways that favor sponsor interests if the agency has not specified restrictive protocols in advance.

“It is evident, however, that this discretion exists in some research and that it can lead to the under-reporting of adverse effects.

Noael, Noael, The Angels Aren’t Singing

NOAEL is regulatory shorthand for No Observed Adverse Effects Level. As in real life, regulatory observation is often a function of what to look for and where to look. The testing protocols known as “Good Laboratory Practices” essentially put blinders on researchers and restrict them to looking for particular things.

If you’re told that you can only look for a skunk, finding a bear can be unfortunate. Likewise, when told to look for tumors or blindness, scientists can — if they choose — ignore and fail to report adverse effects such as diabetes or Alzheimer’s Disease

Despite its glaws, the federal regulatory process revolves around NOAEL and its near-twin sibling, LOAEL (lowest observed adverse effect level).

How The Process Goes

The NOAEL testing process starts with a substance, a test animal and an investigator hired by a corporation, frequently a pay-for-play third party lab that tortures the definition of “independent.”

The corporate or private lab researchers who do nearly all of the testing for regulatory approval,  knows that their client is looking for an allowable level of a substance to be incorporated into something sold to the public, or emitted into waste water, the air or discarded in a dump.

Unlike scientists seeking grants from the National Institutes of Health, the corporate or private lab investigator doing a study for the FDA doesn’t have to prove his/her competency nor do they have to get approval for the design of the testing or the choice of a test animal.

But, they do have to adhere to a cook-book set of record-keeping rules called “Good Laboratory Practice,” which are similar to the lab basics mastered by anyone with an associate’s degree in chemistry, or biology.

They also have to use a rigid set of how to test and what they should look for. However, adverse effects not included in the cookbook can be ignored.

Experiment Design Selection Bias

So, now our corporate lab people neet to design an experiment being sure that whatever they do can be shoehorned into GLP.

GLP actually allows experiment designers to select test animals that are resistant to the substance being tested. That has actually been the case with many such studies on the low-level effects of hormone disruptors.

One frequent bias in corporate BPA studies  continues to be the selection of a particular strain of BPA-resistant lab rat.

It’s important to realize that a lab rat is not just a lab rat. There are many different genetic variations that can have different reactions to different chemicals.

One strain of rat known as the Charles River Sprague-Dawley, is a commonly used one. Indeed, the FDA has large contracts with a breeder to supply this strain to researchers.

Photo By Jean-Etienne Minh-Duy Poirrier [CC-BY-SA-2.0 (http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Photo By Jean-Etienne Minh-Duy Poirrier [CC-BY-SA-2.0 (http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

The problem is that numerous studies continue to confirm that the Sprague-Dawley strain is notoriously INsensitive to BPA. And yet, corporate-paid investigators continue to use it in their studies of BPA.

As one example of this sort of selection bias (along with other experiment design flaws), please see: “Low-Dose BPA Paper In Toxicological Sciences Is Contaminated By Massive Errors & Should Be Pulled.

Sometimes, even after design bias and other manipulations, the experiment results still aren’t favorable enough for regulatory approval. In those cases, industry scientists then argue that the results can be ignored because rats are not people. Can’t Really Rely On Lab Rat Tests.

In other words, corporations and regulators aggressively use favorable study results on rats to prove safety, but reject those tests as irrelevant when the results go the wrong way.

A BPA Experiment: Off To A Bad Start

Testing procedures for any study begin by exposing animals to measured levels of the toxic substance being tested.

Best results are obtained by making the animal exposure conditions as close as possible as those in which humans are exposed.

But here, again, federal experiment guidelines allow tests that are not in line with reality.

For humans, food consumption is the major source of BPA contamination because it is readily absorbed directly by the soft tissues in the mouth and gums and goes directly into the bloodstream. BPA and many other chemicals are far more potent in the bloodstream than in the gastrointestinal tract.

Despite that, with BPA and nearly all other GLP testing, the chemical bypasses the animal mouth and, using a tube and syringe, is fed directly into the stomachs.

Bypassing the mouth in this way allows the animal’s digestive system to help metabolize the BPA, neutralize its effects and keep measured blood levels unrealistically low.

First Experimental Step: Lethal Dose

Exposure concentrations are often high enough too kill all the test animals: Lethal Dose. If a high dose has no effect (according to the predetermined effects in the GLP experiment protocol), then the chemical is declared safe .

If all the animals die, doses are reduced until the LD50 (50% dead) level is reached. That mortality level is just a statistical marker in the testing process.

Compare the information about LD50 from the Canadian government with that from the U.S. Environmental Protection Agency and decide which of them are more interested in helping public understanding. The more people know, the better equipped they are to challenge the status quo.

Moving On From Lethal Levels

After LD50, the concentration of the test substance is decreased.

More effects are noted: rash, blisters, craving for Thin Mints.

Lower and lower doses are administered to the animals until NOAEL is observed: No Observed Adverse Effects.

The dosage tested right before NOAEL is LOAEL: the lowest observed adverse effect level.

Tweaking The Test To Change Results

If the lethal level in the product seeking approval seems too low, the corporate scientist often tweaks the experiment design, perhaps gets a different type of test animal and does it again in search of the lowest number that can be finagled.

Once the corporate study results are sufficiently adjusted into something likely to be approved, the study is then sent to the FDA, EPA or other regulatory agency. Once at the agency, the study is reviewed by a committee – often dominated by bureaucrats and corporate scientists who outnumber any independent or university scientists who may be selected. (Many of those independent scientists on committees eventually resign because they feel they are window dressing and being used to try and bring respectability to decisions they feel are wrong.)

Safety Is A Regulatory Guessing Game

The regulatory committee looks at the study’s LOAEL.

Then, they make a guess at what the allowable limit should be. That guess could be 3 times or a 100 times lower than LOAEL. Or it could be 1,000 times lower.

Regardless, the number is still just a guess.

If the guessed-at number is lower than exists in the company’s existing product or emissions, the corporation argues for a higher level.

It often gets that higher level . And all too often, the bureaucrats involved hope to retire from their government jobs into high-paid corporate jobs with the people they regulate. This is called the “revolving door” and it can be lethal for public health.

Good Lab Practices Ignore Bad Effects

One of many fundamental flaws with GLP is that it is based on 1950s science and does not accept more recent science proving that some substances — such as hormone disruptors — can be more dangerous at low concentrations than than they can at high concentrations.

GLP  and old science make no provision for the evelopment of Type 2 diabetes, cancer or other diseases caused by long-term exposures to low doses of the chemical. They simply cannot understand the most recent science about chemicals that can have powerful effects when present in the same concentrations as human hormones. Or, perhaps it is inconvenient to acknowledge modern science because it can run counter to regulatory approvals..

To understand why very small concentration can be dangerous, please see:

Corporate Studies Exempt From Federal Misconduct Law

Corporate and regulatory science suffers from a severe hypocrisy problem. University and other respectable scientists who receive funding from government agencies  must adhere to a rigid set of ethics, honesty, and rules that are enforced by the Office of Research Integrity (ORI).

“Publicly sponsored research is governed by scientific misconduct regulations that withdraw funding and stigmatize the offending researchers; private research is exempt from this form of regulatory oversight, even when private research forms the primary basis for federal health and safety regulation.”– Equal Treatment for Regulatory Science

While the ORI has been accused of shirking some of its duties, the National Institutes of Health enforces the strictest rules of conduct, of ethics. In addition, it also enforces standards of experiment design and the qualifications of scientists receiving its grants.

Corporations Use Ethics Rules To Harass & Discredit Honest Science

None of the ORI or NIH rules apply to corporate scientists or those who work for for-profit, pay-for-play labs.

However, those paying for unethical science with pre-selected conclusions often use the ORI and NIH rules to harass honest scientists.

“[T]here are anecdotes of industry using the misconduct provisions to harass and discredit scientists whose research is adverse to their interests. Again the disparate oversight of the quality of public versus private research repeats itself,”– Equal Treatment for Regulatory Science

 

 


Equal Treatment for Regulatory Science: Extending the Controls Governing the Quality of Public Research to Private Research,American Journal of Law & Medicine, 30 (2004): 119-54, 2004 American Society of Law, Medicine & Ethics Boston University School of Law, by Wendy Wagner & David Michaels

Glenn W. Suter II & Susan M. Cormier (2014): The Problem of Biased Data and Potential Solutions for Health and Environmental Assessments, Human and Ecological Risk Assessment: An International Journal, DOI: 10.1080/10807039.2014.974499

Footnotes from Equal Treatment for Regulatory Science on use of misconduct laws to harass honest scientists.

Scientific Misconduct Regulations, 40 C.F.R. pt. 50, subpt. A; see generally Robert M. Anderson, The Federal Government’s Role in Regulating Misconduct in Scientific and Technological Research, 3 J. L. & TECH. 121 (1988).
120 Herbert Needleman (whose research on child lead poisoning was pivotal in EPA’s lead phase-out of gasoline) was alleged to have engaged in misconduct. The accusations of misconduct, brought by scientists who consulted with the lead industry, turned out to be meritless, and he was cleared of wrongdoing. See, e.g., Herbert L. Needleman, Salem Comes to the National Institute of Health: Notes from Inside the Crucible of Scientific Integrity, 90 PEDIATRICS 977 (1992); Joseph Palca, Lead Researcher Confronts Accusers in Public Hearing, 256 SCIENCE 437 (1992); Gary Putka, Professor’s Data on Lead Levels Cleared by Panel, WALL ST. J., May 27, 1992, at B5.

Scientific misconduct allegations were also brought against researchers documenting how the “Joe Camel” logo appealed to young adolescents. The charges were brought by an academic affiliated with RJR Reynolds, the holder of the Joe Camel trademark. Paul M. Fischer, Science and Subpoenas: When Do the Courts Become Instruments of Manipulation?, 59 LAW & CONTEMP. PROBS. 159, 160 (1996).

 

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