designing an experiment testing the effectiveness of a drug in phase 3 clinical trials

Name of Student
Professor’s Name
Clinical Trial
27th October, 2015
Designing an Experimentation Testing the Effectiveness of a Drug in Phase 3 Clinical Trial
Materials and Methodology
Selection of Samples
3000 individuals suffering from lung cancer were selected through purposive sampling. The subjects were selected from the Santa Clara Medical Centre. Lung cancer was standardized as a significant tumorous growth in any part of the lungs which was certified by the consultant radiologist as per carcinoma guidelines. The individuals were randomized into various groups as per the protocol of experimental design. Each completing the study was compensated with 500$ for their time during the study period of 1.5 years. A written consent was obtained from each participant as per the protocol of ethical research.

Inclusion Criteria
Individuals aged between 30 years to 60 years were included in the study. Only such individuals were selected, in whom, tumor biomass was significantly diagnosed by the consultant radiologist. Smokers and non-smokers were both included in the study to reduce the effects of confounding bias. Further, male and females were included in the study to reduce the chances of gender bias.
Exclusion Criteria
Individuals below the age of 30 years and more than 60 years were excluded from the trial. Such exclusion criteria were based on phase 2 data, where the safety profiles in such age groups were not conclusive. Moreover, patients who had an insignificant tumor biomass as certified by the radiologist were not included in the study.

Individuals with respiratory disease and pregnancy were also excluded from the study.
Evaluation Index
Computed Tomography Scan was used for radiological diagnosis of tumor morphology on its biomass or size.

Experimental Design
The present clinical trial was a Phase 3 clinical trial and was conducted to evaluate the efficacy and safety of our drug “X” in comparison to Luzapo and placebo. The study was a randomized, placebo-controlled, double blinded trial and ensured minimal chances of bias. The stringent inclusion and exclusion criteria accommodated a wide variety of patients belonging to different genders and confounding habits, chiefly smoking.
The 3000 subjects included 2000 male and 1000 females, with equal proportion of smokers and non-smokers as per gender. All the subjects included in the study were standardized on the size of tumor, body weight, and confounding factors before application of the independent variables (medications or placebo). The study was divided into three groups:
Group 1 = Consisted of 1000 individuals (with an equal number of smokers and non-smokers and equal number of males and females). These individuals received placebo.

Group 2 = Consisted of 1000 individuals (with an equal number of smokers and non-smokers and an equal number of males and females). These individuals received Luzapo.
Group 3 = Consisted of 1000 individuals (with an equal number of smokers and non-smokers and equal number of males and females). These individuals received the experimental drug “X”.
CT scan was performed every three months to document the size of the tumor after initiation of therapy with the respective drugs or placebo. The dosage selected for all the three independent variables were 10mg/day. Statistical tests were done to compare the mean size of tumors (average size of tumors after five consecutive measurements at three months interval) with the initial size of tumor.
Experimental Hypothesis and Statistical Testing
The hypothesis we tested was based on the rejection of null hypothesis. The null hypothesis contended that there is no statistically significant difference between the tumor sizes treated either with placebo, Luzapo or the experimental drug “X”. Any difference must have occurred due to experimental bias. The null hypothesis was rejected when the p-value was less than 0.05, since 0.05 was the chosen level of significance. Hence, our experimental hypothesis was to prove that the experimental drug “X” significantly reduced tumor mass in comparison to placebo and Luzapo. The test of significance conducted was the z test and all calculations were done through the Minitab Software.
Results
Table 1: Descriptive Statistics
Initial Tumor Size
(cm) Final Tumor Size (cm) Age Weight
Group 1
(Placebo) 1.5 + 0.02 1.57 + 0.02 45.8+ 2.3 54.8+ 2.3
Group 2
(Luzapo) 1.52+ 0.012 1.03+ 0.18 44.7+ 1.8 54.7+ 1.8
Group 3
(Experimental Drug “X”) 1.51+ 0.03 0.87 + 0.02 45.3+ 0.72 54.9+ 0.8
The descriptive statistics revealed that the various groups were adequately standardized on size of tumors, Age and Weight of the Individuals. Further, the groups well also standardized on the confounding variables considered in the study. The homogeneity of the population was well maintained. The confounding variables considered for the study were smoking habits, symptomatic relief of a cough and vitamins prescribed as adjunct for treatment.

The standardization was well documented since p >0.05 between the treatment groups on the size of tumors (initial size before treatment was initiated), Age and Weight of the Individuals. Thus, the baseline characteristics were considered to be same and the treatment options were administered as per experimental design. The tumor sizes varied in all the groups after treatment was completed in comparison to the initial size of tumors in various groups. Statistical tests were implemented to judge the significance level of such variations as per Fig 1 and Fig 2.

Fig 1: Represents the comparison of mean tumor sizes after treatment was completed with the three treatment regimes considered in the trial. The tumor size was significantly reduced in the Luzapo group compared to placebo (p<0.001), tumor size was significantly reduced in the Drug “X” group compared to placebo (p<0.0001) and ultimately tumor size was significantly reduced in the Drug “X” group compared to Luzapo (p<0.005).

Fig 2: Represents the comparison of mean tumor sizes after treatment was completed with the initial tumor sizes in the different groups, considered in the trial. The tumor size was not significantly reduced in the Placebo group before and after treatment variable (placebo) was administered (p>0.05), tumor size was significantly reduced in the Drug “X” group before and after treatment variable (Drug “X”) was administered (p<0.00001), and tumor size was significantly reduced in the Luzapo group, before and after treatment variable (Luzapo) was administered (p<0.001)

Fig 3: Reflects the % reduction in the size of tumors after application of treatment variables. Drug “X” reduced the size of the tumor by 57.5%, Luzapo reduced it by 31.5% while Placebo marginally increased tumor size by 4%.
Discussion & Conclusion
The results of phase 3 clinical trial clearly indicated that the Experimental drug ‘X” used in this trial, significantly reduced the initial size of a tumor in comparison to Luzapo and Placebo respectively. Moreover, the trial further reflected that the tumor sizes significantly varied between initial and final sizes on Drug “X” and Luzapo. However, there was no significant difference between the size of tumors before and after administration of placebo. Such an effect with placebo is expected because placebo did not contain any active ingredient of anticancer drugs.

Such an observation was based on the fact that the p-values for the respective comparisons were less than 0.05. This means that out of 100 observations the variation in size of tumors as a matter of chance is less than 5. Hence, the null hypothesis was rejected and the experimental hypothesis was accepted. The null hypothesis contended that there is no statistically significant difference between the tumor sizes treated either with placebo, Luzapo or the experimental drug “X” , and also before and after the treatment variables are applied. The null hypothesis should have been only accepted if the p value was greater than 0.05 for the comparisons used in the trial. The acceptance of null hypothesis signifies that out of 100 observations the variation in size of tumors as a matter of chance is greater than 5. Hence, it meant that happening by chance factors of random sampling is very and treatment variables have not significantly affected the variations in tumor sizes.
Thus, the results reflected that Drug “X” was more efficacious than either Luzapo or Placebo in reducing the size of tumors. Such findings should be correlated with other biochemical and oncological testing, to designate Drug “X” as a potent anticancer agent. However, the Phase 3 trials were encouraging and hence Phase 4 trial may be carried out in a large population in the Post-Marketing phase.

The experimental design considered in this trial was quite robust as Drug “X” was compared to Placebo. Such comparison indicated that indeed Drug “X” contain the active anti-cancer agents that were instrumental in reducing the size of tumors before going on for a direct head to head comparison with Luzapo. The study was also robust due to the fact the initial tumor sizes were meticulously standardized before the start of the experimentation. Such standardization helped to analyze the % reduction of tumor sizes with each of the treatment variable. Perhaps “Drug X” acted as a potent apoptotic agent, as surveyed from existing literature and pharmacokinetics.

The limitations of the study were the limitation in diversity of the sample and lack of multi-centric approach, as because only one hospital was considered for the study. Moreover, the study could have been carried out as a cross over trial during 1.5 years. Such design would have accommodated the placebo group from getting exposure to any one of the anticancer regimes, either Drug “X” or Luzapo. Cross-over design might have potentiated the ethical basis of this trial.