Ethics in Healthcare: A Critical Analysis of the ADAPT Clinical Drug Trial

Running head: ARGUMENTATIVE ESSAY
Ethics in Healthcare
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ARGUMENTATIVE ESSAY1
Introduction:
Clinical drug trials have become increasingly popular in the field of healthcare
research. Clinical trials serve as evidence to find best treatment option for patients.
Successful clinical trials serve as a licensure to deliver evidence based interventions
that are prescribed by healthcare practitioners who would otherwise make a clinical
judgement merely on the basis of their experience which could be biased and
misleading. On account of the importance of the clinical trial results it is vital to
ensure that trials are conducted ethically and the results obtained are scientifically
sound as well as maintain patient autonomy and safety (Deichmann, Kousel-Wood,
& Breault, 2016). One of the clinical drug trial studies The Alzheimer’s Disease Anti-
inflammatory Prevention Trial (ADAPT) conducted in 2006 intended to evaluate the
conventional NSAID naproxen sodium and the selective COX-2 inhibitor celecoxib
for the primary prevention of Alzheimer’s dementia (AD). However, another drug trial
Adenoma Prevention with Celecoxib (APC) was conducted in 2004 and this trial
reported increased cardiovascular risks accompanied with the use of celecoxib. On
the basis of the increased risk factors, the ADAPT Steering Committee suspended
the treatment intervention and enrolment of the subjects for conducting the clinical
trial.
Overview of the trial:
This trial was sponsored by the United States National Institute on Aging, and
the recruitment process initiated from the year 2001. The blue print of the experiment
suggested that 2625 participants would be recruited who would then be randomised
into three arms: naproxen, celecoxib and placebo. It was then assumed that the trial
would run for seven years. However, the experimental study came to an abrupt end

ARGUMENTATIVE ESSAY2
when the decision was undertaken by the NIH to terminate the study early. It should
be mentioned here that the decision undertaken was based on the part of results
from other studies that have showed an increased risk of certain medical adverse
events, such as myocardial infarction and stroke in patients taking celecoxib and
other types of COX-2 inhibitors. However, this data was not estimated at the time of
designing the trial. However, the ADAPT studies have further investigated the
chances of the medical adverse events (Martin, 2006).
The decision to stop a clinical trial early is undertaken mainly to minimize the
harm and maximize the benefits for the participants. Research studies suggest that
when the results show no justified cause for subjecting the participants to potential
risks by continuing the trial, the trial must be stopped (Streiner, 2019). However,
stopping the clinical trial early needs to be grounded by the ethical principles. In the
ADAPT trial, there were four ethical considerations that were applied when the NIH
decided to stop the trial early simply by just looking at the cardiovascular risks in
ADART.
Scientific Validity:
Firstly, the purpose of a clinical drug trial is to investigate whether the study
drug is safe and effective for patients and it must closely approximate the accurate
impact of the drug and should not be misleading. This requires the study procedure
to follow the scientific standard and to ensure the results confer to scientific validity
(Wears, 2015). Statistical theory and experiential evidence imply that early stopping
of a drug trial can generate inconclusive data that can compromise with the scientific
validation of the results. However these trials are still important to patients, as they
help to determine conditions such as disease-free survival, symptom control, quality

ARGUMENTATIVE ESSAY3
of life, and adverse impact of treatment (Bassler, Montori, Briel, Glasziou, & Guyatt,
2008). The ADAPT trial was stopped due to evidence from APC trial which
demonstrated an increased risk of cardiovascular and cerebrovascular diseases,
among patients that consumed celecoxib and other types of COX-2 inhibitors.
Therefore, early termination of the drug failed to evaluate the effect of conventional
NSAID naproxen sodium and the selective COX-2 inhibitor celecoxib for the primary
prevention of Alzheimer’s dementia (AD) which was the primary study outcome.
Furthermore, truncated trials have been mentioned to overestimate treatment
effects (Bassler et al., 2008). In the ADAPT study, participants who experienced
cardiovascular or cerebrovascular death, MI, stroke, CHF, or TIA in the celecoxib-,
naproxen-, and placebo-treated groups were 28/717 (5.54%), 40/713 (8.25%), and
37/1070 (5.68%), respectively which summed up a hazard ratio (95% confidence
interval [CI]) for celecoxib of 1.10 (0.67–1.79) and for naproxen of 1.63 (1.04–2.55).
Antihypertensive treatment was initiated in 160/440 (47.43%), 147/427
(45.00%), and 164/644 (34.08%) which produced a hazard ratio (CIs) of 1.56 for
celecoxib (1.26–1.94) and 1.40 for naproxen (1.12–1.75) (Martin, 2006). The number
of accrued outcome events was small, but the overestimated treatment effect can be
huge that violates the ethical research requirement of scientific validity. Subsequent
use of overestimated treatment results by clinicians to make clinical decisions also
violates the ethical requirements of social value and violates a favourable risk–
benefit ratio (Murad et al., 2017).
Social Value:
On the other hand, it is very important that investigators comply with the
ethical obligations while dealing with research participants. However, there might be