Biological plausibility
Encyclopedia
In epidemiology
and biomedicine
, the term biological plausibility refers to the proposal of a causal association — a relationship between a putative cause and an outcome — that is consistent with existing biological and medical knowledge.
Biological plausibility is one component of a method of reasoning that can establish a cause-and-effect relationship between a biological factor and a particular disease or adverse event. It is also an important part of the process of evaluating whether a proposed therapy (drug, vaccine, surgical procedure, etc.) has a real benefit to a patient. This concept has application to many controversial public affairs debates, such as that over the causes of adverse vaccination outcomes
.
Biological plausibility is an essential element of the intellectual background of epidemiology. The term originated in the seminal work of determining the causality of smoking-related disease (The Surgeon General’s Advisory Committee on Smoking and Health [1964]).
Other important criteria in evaluations of disease and adverse event causality include consistency, strength of association, specificity and a meaningful temporal relationship. These are known collectively as the Bradford-Hill criteria
, after the great English
epidemiologist who proposed them in 1965. However, Austin Bradford Hill
himself de-emphasized "plausibility" among the other criteria:
or biologic has been termed "plausibility building". This involves the gathering and analysis of biochemical, tissue or animal data which are eventually found to point to a mechanism of action or to demonstrate the desired biological effect. This process is said to confer biological plausibility. Since large, definitive RCTs are extremely expensive and labor intensive, only sufficiently promising therapies are thought to merit the attention and effort of final confirmation (or refutation) in them.
In distinction to biological plausibility, clinical data from epidemiological studies, case report
s, case series
and small, formal open or controlled clinical trials may confer clinical plausibility. According to the strictest criteria, a therapy is sufficiently scientifically plausible to merit the time and expense of definitive testing only if it is either biologically or clinically plausible. It has been observed that, despite its importance, biological plausibility is lacking for most complementary and alternative medicine
therapies.
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
and biomedicine
Biomedicine
Biomedicine is a branch of medical science that applies biological and other natural-science principles to clinical practice,. Biomedicine, i.e. medical research, involves the study of physiological processes with methods from biology, chemistry and physics. Approaches range from understanding...
, the term biological plausibility refers to the proposal of a causal association — a relationship between a putative cause and an outcome — that is consistent with existing biological and medical knowledge.
Biological plausibility is one component of a method of reasoning that can establish a cause-and-effect relationship between a biological factor and a particular disease or adverse event. It is also an important part of the process of evaluating whether a proposed therapy (drug, vaccine, surgical procedure, etc.) has a real benefit to a patient. This concept has application to many controversial public affairs debates, such as that over the causes of adverse vaccination outcomes
Vaccine controversy
A vaccine controversy is a dispute over the morality, ethics, effectiveness, or safety of vaccinations. Medical and scientific evidence surrounding vaccinations generally demonstrate that the benefits of preventing suffering and death from infectious diseases outweigh rare adverse effects of...
.
Biological plausibility is an essential element of the intellectual background of epidemiology. The term originated in the seminal work of determining the causality of smoking-related disease (The Surgeon General’s Advisory Committee on Smoking and Health [1964]).
Disease and adverse event causality
It is generally agreed that to be considered “causal”, the association between a biological factor and a disease (or other bad outcome) should be biologically coherent. That is to say, it should be plausible and explicable biologically according to the known facts of the natural history and biology of the disease in question.Other important criteria in evaluations of disease and adverse event causality include consistency, strength of association, specificity and a meaningful temporal relationship. These are known collectively as the Bradford-Hill criteria
Bradford-Hill criteria
The Bradford Hill criteria, otherwise known as Hill's criteria for causation, are a group of minimal conditions necessary to provide adequate evidence of a causal relationship between an incidence and a consequence, established by the English epidemiologist Sir Austin Bradford Hill in 1965.The...
, after the great English
English people
The English are a nation and ethnic group native to England, who speak English. The English identity is of early mediaeval origin, when they were known in Old English as the Anglecynn. England is now a country of the United Kingdom, and the majority of English people in England are British Citizens...
epidemiologist who proposed them in 1965. However, Austin Bradford Hill
Austin Bradford Hill
Sir Austin Bradford Hill FRS , English epidemiologist and statistician, pioneered the randomized clinical trial and, together with Richard Doll, was the first to demonstrate the connection between cigarette smoking and lung cancer...
himself de-emphasized "plausibility" among the other criteria:
It will be helpful if the causation we suspect is biologically plausible. But this is a feature I am convinced we cannot demand. What is biologically plausible depends upon the biological knowledge of the day. To quote again from my Alfred Watson Memorial Lecture [1962], there was
- "…no biological knowledge to support (or to refute) Pott
Percivall PottSir Percivall Pott London, England) was an English surgeon, one of the founders of orthopedy, and the first scientist to demonstrate that a cancer may be caused by an environmental carcinogen.-Life:...
’s observation in the 18th century of the excess of cancer in chimney sweepChimney sweepA chimney sweep is a worker who clears ash and soot from chimneys. The chimney uses the pressure difference caused by a hot column of gas to create a draught and draw air over the hot coals or wood enabling continued combustion. Chimneys may be straight or contain many changes of direction. During...
s. It was lack of biological knowledge in the 19th that led to a prize essayist writing on the value and the fallacy of statistics to conclude, amongst other “absurd” associations, that 'it could be no more ridiculous for the strange who passed the night in the steerage of an emigrant ship to ascribe the typhusTyphusEpidemic typhus is a form of typhus so named because the disease often causes epidemics following wars and natural disasters...
, which he there contracted, to the verminVerminVermin is a term applied to various animal species regarded by some as pests or nuisances and especially to those associated with the carrying of disease. Since the term is defined in relation to human activities, which species are included will vary from area to area and even person to person...
with which bodies of the sick might be infected.' And coming to nearer times, in the 20th century there was no biological knowledge to support the evidence against rubellaRubellaRubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
."
In short, the association we observe may be one new to science or medicine and we must not dismiss it too light-heartedly as just too odd. As Sherlock HolmesSherlock HolmesSherlock Holmes is a fictional detective created by Scottish author and physician Sir Arthur Conan Doyle. The fantastic London-based "consulting detective", Holmes is famous for his astute logical reasoning, his ability to take almost any disguise, and his use of forensic science skills to solve...
advised Dr. Watson, "when you have eliminated the impossible, whatever remains, however improbable, must be the truth."
Treatment outcomes
The preliminary research leading up to a randomized clinical trial (RCT) of a drugDrug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
or biologic has been termed "plausibility building". This involves the gathering and analysis of biochemical, tissue or animal data which are eventually found to point to a mechanism of action or to demonstrate the desired biological effect. This process is said to confer biological plausibility. Since large, definitive RCTs are extremely expensive and labor intensive, only sufficiently promising therapies are thought to merit the attention and effort of final confirmation (or refutation) in them.
In distinction to biological plausibility, clinical data from epidemiological studies, case report
Case report
In medicine, a case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports may contain a demographic profile of the patient, but usually describe an unusual or novel occurrence....
s, case series
Case series
A case series is a medical research descriptive study that tracks patients with a known exposure given similar treatment or examines their medical records for exposure and outcome. It can be retrospective or prospective and usually involves a smaller number of patients than more powerful...
and small, formal open or controlled clinical trials may confer clinical plausibility. According to the strictest criteria, a therapy is sufficiently scientifically plausible to merit the time and expense of definitive testing only if it is either biologically or clinically plausible. It has been observed that, despite its importance, biological plausibility is lacking for most complementary and alternative medicine
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....
therapies.