Present Medical Research: Is it Really Original Research Anymore?
Introduction
I have been a faculty member at several medical institutions in
USA for almost 44 years. I am thoroughly disappointed at the quality
of present medical research in comparison to research conducted
until the turn of the century. I propose the following reasons for the
decline in the quality.
Epidemiological studies
Retrospective studies were then shunned by most prestigious
and established journals. Presently, a large majority of the articles
published in these same journals happen to be conducted by a
retrospective design. Unfortunately, almost all these studies are
epidemiological in nature demonstrating association between one
parameter and another using a statistical analysis establishing
‘Relative Risk or Hazard Ratio’. Moreover, most of these studies
conduct ‘multivariate’ analyses and often artificially eliminate
multiple variables to satisfy the associations between pre-decided
parameters [1]. Finally, RR is almost always statistically significant
even with a miniscule ratio (1.1) because of data retrieval in very
large populations obtained from registries as well national health
and insurance websites via internet and electronic medical records.
It must be mentioned that statistical significance often does not
translate into clinical significance.
Most frequent design used in these retrospective analyses is to
divide a population into tertile or quartile groups based on levels
of a metabolite and determination of RR between the metabolite
with predecided outcomes. Almost none of these studies document
significant correlations between the metabolite and outcomes
or attempt to establish pathophysiologic or cause and effect’
relationships. The prime example is ‘Vitamin D deficiency’ and
almost all ills in mankind [2]. In fact, vitamin D supplementation
has apparently evolved into a big industry despite total lack of
evidence showing remission or even improvement in almost all
these disorders following vitamin D supplementation even with
megadoses [2]. Association between oral antihyperglycemic agents
and cardiovascular morbidity as well as mortality in subjects
with type 2 Diabetes without consideration of variability of other
important metabolites such as HbA1c, lipid panel and other
cardiovascular risk markers using retrospective registry analysis
is another prominent example [3-5]. List of similar examples is
too large and is beyond the scope of this essay. Unfortunately, this
design is being implemented to document increased incidence of
a known adverse effects of the drug in comparison to placebo, e.g.
greater relative risk of hyponatremia and hypokalemia with a use
of diuretic in comparison to other non-diuretic comparators [6].
Sooner than later, a study may appear in the literature showing
increased prevalence of hypoglycemia in subjects with diabetes
using insulin in comparison to normal subjects administered a
placebo.
Meta-analysis
During the last 20 years of the 20th century, medical research
funding in USA by private foundations, pharmaceutical companies,
major institutions as well as the governmental agencies declined
precipitously. Moreover, studies with enrollment of large
populations, e.g. over a thousand were not funded by governmental
agencies such as National Institute of Health probably because of
earlier government sponsored clinical trials such as University
Group Diabetes Program creating major controversies [7-9].
Moreover, many long-term population studies such as very wellrespected
Framingham cardiovascular outcome trial primarily
involved Caucasian families [10,11]. Unfortunately, the results
of this study are still being applied to subjects belonging to other
ethnic groups, e.g. African Americans, Asians, South Americans etc.
As a result, the lack of adequate funding for studying large
populations gave way to a new study design of ‘meta-analysis’
requiring very little or no funding.
Thus, meta-analysis has become ‘poor researcher’s design to
examine data in a large population by involving multiple studies
with small populations of subjects. The methodology has become
extremely accessible since the advent of internet because of easy
retrieval of literature on websites such as ‘pub med, medline, google
search’ etc. Easy access to interested colleagues and a statistician in
the department of a major medical institution is primary requisite.
Thus, meta analyses are apparently a ‘second hand research’ a
poor substitute for a large population study. Unfortunately, even
the pharmaceutical companies are taking advantage of this design
by reporting individual clinical trial with enrollment of relatively
small populations and reporting a meta-analysis involving the
same clinical trials arriving at almost identical conclusions at a
later date. For example, many of the individual clinical trials using
GlP1 Receptor agonists failed to report increased prevalence of
acute pancreatitis and Meta-analysis arrived at the same conclusion
obviously because it included the same individual clinical trials [12].
Similar meta analyses have been reported using clinical trials with
other drugs as well [13,14]. A major drawback of the meta-analysis
is the biases of the researchers regarding inclusion and exclusion
criteria for the small studies depending on the similarities of the
subjects, the methodologies as well as predetermined outcomes.
Hence, the conclusions are are frequently questionable and must
be critically examined and interpreted. These aforementioned
limitations of meta-analysis design are recently very well described
[15-17].
Multinational clinical trials
Many major pharmaceuticals have recently embarked upon
worldwide multinational clinical trials examining the efficacy as
well as safety of their drugs in treatment of chronic disorders, e.g.
Diabetes, Hypertension, dyslipidemia on cardiovascular outcomes
etc [18]. Apparently, there are several major flaws in the designs
of these trials [19-21]. Reporting of the data in the total population
irrespective of diversity of ethnicity of the subjects, differences in
prominent pathophysiology of disorders in populations with these
diversities is a major drawback. Decline in insulin secretion in lean
subjects especially of southeast Asian origin in contrast to the rise
in insulin resistance in obese Americans with type 2 Diabetes [22-
24] or increase in cardiac output and circulating blood volume as
a major causative contributor in African Americans in contrast to
rising peripheral vascular resistance as a main pathophysiologic
factor of hypertension in subjects with other ethnicities are
distinctly of importance in the outcomes.
Moreover, variability in prevalence of disorders in populations
of different diverse backgrounds is also likely to alter predetermine
outcomes. Alternatively, lack of uniformity of methodology because
variability of use of medications and goals of therapy for these
disorders based on criteria developed by medical organizations of
individual nation may be another fraudulent factor. Moreover, the
uniformity in the methodology is even further compromised by
leaving the choice of the strategy of management of the disorder to
the discretion of the individual investigator. Finally, sponsorships
and funding of these trials by pharmaceutical companies also raise
questions regarding the integrity and reliability of the conclusions
since the major incentive for the sponsors is to obtain approval
and marketing of drugs in order to generate profits and improve
their financial future. Therefore, it is apparent that the data in
these trials must be confirmed by additional repetitive results
conducted by institutions, agencies or investigators independent of
and not connected in any way with pharmaceuticals. Alternatively,
the initial trials must be conducted by the same independent
entities in order to establish the integrity, purity and reliability
of. conclusions. Recently, the integrity and reliability of even
short-term clinical trials has also been questioned because of the
participation by a few same investigators (20%) in development of
the design and performance of most (80%) of the trials [25-27].
It is apparent that these few investigators have created ‘clinical
trial mills’ by developing a data base of subjects who hop from one
trial to another thus compromising the integrity and reliability.
In conclusion, recent medical research appears to utilize inferior
designs in terms of methodologies and may also be devoid of
highest integrity, accuracy and reliability.
Prevalence of Cardiac
Arrhythmias among Chronic Obstructive Pulmonary Disease Patients
Admitted to Jimma University Medical Center - https://biomedres01.blogspot.com/p/blog-page_10.html
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