Clinical study design is used to establish the statistical parameters for the scientific hypothesis being tested. In 1964, Zidovudine (AZT) was synthesized at Wayne State University for cancer therapy under the US National Institute of Health’s grant (Sriram, & Yogeeswari, 2010). AZT was the first clinically tested and approved drug for the treatment of HIV or AIDS patients (FDA, 2009). The clinical trial with AZT in humans began in 1985 with a phase I clinical trial involving HIV positive human subjects to determine tolerable dose of the retrovirus medication. Consequently, after the dosage determination, the clinical trial was cleared to proceed into a phase II clinical trial in a randomized double blinded placebo-treatment trial involving approximately 260 HIV+ or AIDS subjects at a given site (Amabile, 1989).

Based on a retrospective evaluation of the trial conducted with AZT from the 1985 clinical trial and its approval by the FDA; the ethical issues surrounding the 1985 AZT clinical trial design is overwhelming (Amabile, 1989). For a terminal illness such as HIV/AIDS, having a double blinded placebo-controlled study design may constitute an unethical practice in the sense that HIV positive or AIDS subjects receiving placebo at the time of the clinical trial were not deriving any beneficent from the trial, thus resulting in the high mortality rate among the subjects’ population within the placebo group (Amabile, 1989). Another mistake is that there was not enough study-time for the safety-efficacy assessment of AZT during the clinical trial. The trial started in 1985 and AZT was approved in 1987, thus becoming the fastest medicinal product approved by the FDA in record time (Amabile, 1989). It was also the most expensive drug after the approval was granted.

Moreover, the greatest bottleneck during the clinical study was the ambiguity of the inclusion/exclusion criteria, one which involves the stage of HIV infection or AIDS disease within the human subjects’ population during the trial, which brings in question the uniformity of the subjects selection, and whether the stage differences affected the mortality rate in either placebo or experimental group. Perhaps, the ideal situation in this study would have been to conduct a comparative study, but, unfortunately, at the time (1985) there was no known approved medicinal therapy for the treatment of AIDS or reduction of HIV viral load. Nonetheless, the Burroughs-Wellcome Company of North Carolina managed to develop an application for HIV/AIDS among all odds, which clearly had many flaws. Apparently, scientific innovative application may not be enough justification to maintain the tenets of ethical scientific research without maintaining the ethical tenets in the Belmont report (Justice, beneficent and respect), in any scientific discovery. For this reason, an observational study such as a cohort or incidence longitudinal or a case-series study would have been appropriate and perhaps ethical instead of a placebo-controlled study. A cohort study will allow all HIV infected subjects or AIDS patients the chance to receive the active drug with potential expectation of beneficence, and probably avoid or reduce the mortality rate observed in the study or control group (Gay, 1999). It could have been much easier to follow the T4 cell (CD4) counts, relative blood count, viral load and any other relative phenotype under observational study in determining whether the drug is effective, safe or ineffective without having sick or infected subjects receiving the placebo compound and enduring the fatal pain through the trial.

Observational case series study is another way to determine “factors” associated with how HIV infected patients end up developing AIDS, while some do not. The case series study will show a descriptive observational study describing the manifestation, clinical course, and prognosis of the AIDS condition. The population under the inclusion/exclusion criteria should involve homosexuals, heterosexual, diverse race, drug users infected with HIV, and in all cases both men and women at different age group should be included in the study. In retrospect, another key measurable variable is the mode of infection and age at the time of infection/race. This criteria may account for the inherent effect of genomic polymorphism.

Another study method could be a case-series study. A case-series study is a descriptive retrospective or prospective clinical studies used assessing the risk-exposure in relation to the incidence or outcome of a disease or condition, such as the HIV+ patient’s tendencies in developing or not developing AIDS under similar treatment determinants. It may also involve reviewing subject’s medical record as well, which may give an idea of the subjects’ medical history, physiological state and pre-existing condition, which could also be used to analyze the vulnerability status of opportunistic disease such as AIDS etiology (Gay, 1999).

A placebo-controlled trial can without any doubt produce the best scientific result if designed appropriately, but there is always the possibility of the placebo effect in clinical trials (Bren, 2007). However, the ethical context and validity of placebo-controlled clinical trials is a case-by-case basis. For this reason, it may be deemed unethical introducing placebo-controlled design in a terminally ill subjects’ population. The basic clinical trials’ tenet and purpose are the presumption of the “intent to treat” and that subjects by all possible account should derive some “beneficent” in participating in a clinical trial.

Hence, if any medicinal product produces more harmful adverse events to subjects than a placebo would have, then the benefit-risk assessment is not beneficial to the human subjects. Therefore, the benefit of conducting phase I trial within healthy individuals is to determine the plausibility of these factors and then once determined, the safe dose appropriate for treatment can be used in the phase II and phase III clinical trials. Unfortunately, the problem with the AZT clinical trials was that all these criteria were not followed appropriately. Perhaps, the urgency to introduce any HIV/AIDS therapy at the time outweighed any potential risk-assessment process, which is not an ethical justification of the facts. Hence, considering the ethical principle of clinical trials, using a placebo-controlled design in the AZT trial is still an unethical medical practice. Thus, the ideal study condition for a new drug, such as the AZT that has no comparable therapy for the disease condition being tested could involve a study designed among terminal patients using the experimental drugs and concomitant medications if available, then monitor the viral load, physical conditions, CD4 count etc of patients to determine how harmful or the beneficial effect of the investigational medicinal product.

The case study for testing AZT among the AIDS population within a study design that did not have very strict inclusion and exclusion criteria was produced preventable fatal outcomes. Hence, lead to observations that did not have any scientific proof. Inclusion and exclusion criteria should be used to establish the desired study population leading to the information needed to answer the scientific question (Dawson, & Trapp, 2004). The population and sample size used in the 1985 AZT clinical trials have no strict parameters, and hence the study resulted in false outcomes that did not have any relevance to the research study or question.

References

Amabile, T. (1989). Against all odds: Inside statistics. Retrieved from http:// www.learner.or g/resources/series65.html

Bren, L. (2007). The advancement of controlled clinical trials. FDA Consumer, 41(2), 23–30. Retrieved from http://ezp.waldenulibrary.org/login?url=http://search.ebscohost.com /login.aspx?direct=true&db=rzh&AN=2009533805&site=ehost-live&scope=site.

Dawson, B., & Trapp, R. G. (2004). Basic & clinical biostatistics. New York: Lange Medical Books-McGraw-Hill, Medical Pub. Division.

Food and Drug Administration (FDA). (2009).  HIV/AIDS historical timeline 1981-1990.  Retrieved from http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ HIVand AIDSActivities/ucm151074.htm

Gay, J. (1999). Clinical epidemiology & evidence-based medicine glossary: Clinical study design and methods terminology. Retrieved from http://www.vetmed.wsu.edu/courses- jmgay/GlossClinStudy.htm.

Sriram, D. & yogeeswari. P. (2010).  Medicinal chemistry ( 2^nd ed.). Retrieved from http://books.google.com/books?id=tUSLclf_NoQC&pg=PA11&lpg=PA11&dq=1964+AZT+was+synthesized+at+Wayne+State+University+as+a+treatment+for+cancer+under+a+NIH+grant.&source=bl&ots=iZEWJL969D&sig=UWtThOKN4j7O4wwL_3JAid_T7ng&hl=en&sa=X&ei=YSAMU7ahCY6CogTiwYG4Bg&ved=0CDUQ6AEwAg#v=onepage&q=1964%20AZT%20was%20synthesized%20at%20Wayne%20State%20University%20as%20a%20treatment%20for%20cancer%20under%20a%20NIH%20grant.&f=false

Venable,T. (2012). Protocol and initial concept. [Walden DVD]. Retrieve from https://class .waldenu.edu/webapps/portal/frameset.jsp?tab_tab_group_id=_21&url= %2Fwe bapps%2Fblackboard%2Fexecute%2Flauncher%3Ftype%3DCourse%26id %3D_1373257_1%26url%3D