Clinical trial design for Cholestease dosage and side effects

¶ … dosage levels of Cholestease on Serum Cholesterol levels and the side effects associated with them in human beings.

Cholesterol has been a major media issue in recent years, especially the negative effects on the heart and its role in the development of heart disease. There have been many studies that indicate a connection between serum cholesterol heart disease and depression (1-3). Developing new methods to lower serum cholesterol has become a major industry in recent years. Currently the leaders in the industry are American Pharmaceutical giants, Pfizer, Merck, and Warner-Lambert (1), who have developed medications that lower cholesterol.

The Endicon corporation recognizes the potential market in developing a drug that will significantly lower serum cholesterol without the side effects associated with long-term use of the drugs currently on the market. In addition, we recognize the potential of developing a British Product, primarily marketed in Great Britain. Endicon has been conducting research on a new drug that was recently developed by them and has been conducting preliminary studies on the efficacy and long-term effects of the new drug in laboratory animals. Results have been positive and it is now time to begin trials to test the efficacy and proper dosage needed to control serum cholesterol in human beings. The study will also examine any long-term side effects associated with the new drug. The market name of the new drug will be Cholestease.

Problem Statement

Currently there are several competitor drugs on the American market; however, they have yet to be approved for use in Great Britain. There are no current competitors in the British

Market that manufacture drugs for the purpose of lowering cholesterol. In addition, the drugs currently on the market in the United States are linked to serious side effects with prolonged usage (2). The Endicon Corporation has recently completed trials on a new drug that has conclusively lowered serum cholesterol levels in laboratory rats to normal levels within six weeks after beginning the medication. In addition, in longitudinal studies, prolonged usage of the new drug does not seem to have the serious side effects with drugs currently on the market.

With positive results indicating lower serum cholesterol levels in laboratory rats taking Cholestease and no serious side effects indicated, it is now time to begin preparation for human trials. The purpose of these trials will be to establish the most effective dosage of Cholestease in human beings, and to establish the most efficient dosage level. The most efficient dosage will be the one that has the most significant effect on lowering serum cholesterol, while at the same time, with the least amount of side effects.

Research Questions

The research questions to be answered in this study are exploratory in nature, rather than conclusive in nature. The primary purpose of this study is to determine the correct dosage of Cholestease in human beings. The proper dosage is not known at this time and this research will be designed as a preliminary step for further, more conclusive studies in preparation for marketing of the product. The first research question to be answered will be, "What is the most effective dosage for lowering serum cholesterol in human beings using Cholestease as a primary therapy?" The second research question will be, "What dosage of Cholestease has the fewest side effects?" The third research question will be the culmination of the first two research questions and will ask the question, "What dosage of Cholestease is the most effective at lowering serum cholesterol levels, while at the same time, having the least side effects. This will be used to determine proper clinical levels of the drug and determine administration guidelines for medical professionals once the drug is approved and marketed.

Sample Population

This study will be conducted using four test groups and one control group of patients. All participants in the study will be referred from endocrinologists and determined to have high cholesterol that has been uncontrollable by other non-drug means. The study will consist of 250 patients, with 50 patients in each category. All patients will be given a strict diet to follow for the duration of the test in order to control for any other factor, such as dietary cholesterol intake, that could skew the results of the test. The patients will be on an identical exercise schedule and will be considered to be at an average stress level. They will be of approximately the same weight and will not consist of any person considered to be obese, as this could skew the results as well. Demographic information will be collected and used as a means to eliminate biases due to demographic factors that may effect the results. Baseline cholesterol levels will be taken prior to the beginning of the trial.

Method

The control group will be on the same diet, exercise plan and from the same general sample population as the experimental groups and will serve to help detect any errors in the conduct of this survey. This group will act as a baseline by which to measure the cholesterol lowering effects of Cholesterease on the experimental groups. This group will also serve to identify any side effects or conditions that are not a result of the usage of Cholesterease.

The remainder of the sample population will be divided into for groups. The first group will be administered 5 mg of Cholesterease two times daily. The second group will be given 10 mg daily, the third group 15 mg daily and the fourth group will be given 20 groups daily. Each group will take half of the daily dosage two times a day. These levels were determined from a calculation based on the dosages that were proven to be effect on the laboratory rats.

The trial will run for six weeks. Each week the participants will be asked to get their cholesterol levels measured. This will help to determine if a particular dosage acts to lower cholesterol faster than other dosages. The results will be entered into a spreadsheet program and analyzed for significant difference in the performance of various dosages. If at any time a patient demonstrates adverse effects from the drug, they will be pulled from the study as indicated by their physician.

Data Analysis

Data will be analyzed using descriptive statistical techniques and will test for significance in the lowering of cholesterol between groups and also between each group and the control group. A p-value of.05 will be used to indicate significance between various groups. The group proving to be the most effective will be the on that shows the greatest degree of lowering cholesterol as measured against the control group. The data will be cross-tabulated between demographic groups to help detect if there is any sample bias within the sample population hat may skew the results.

Delimitations

This research will be exploratory in nature and will serve to help determine within what range the correct may fall in the sample population. The results will only be applicable to the sample population being studied and should not be used to determine proper dosage for any particular patient in the clinical setting. Once the proper dosage range is found according to this study further testing will have to be conducted to determine if that is indeed the clinically correct dosage.

There are many factors that may effect the results of this study and these factors must be considered in the usage of this information for clinical purposes. There are many factors that effect a person's ability to maintain a healthy serum cholesterol level, including diet, exercise levels, stress levels and many individual differences that cannot be determined such as metabolism (5-8). It will not be possible to foresee or eliminate all of the factors that may have an effect on the results of this study. However, statistical controls will be used to help eliminate the severity of any of the effects of these factors. It is expected that these results will be reflective of results that would be found in the general population.

Conclusions

The results of this study are expected to effectively answer the research questions. Even though this study has many potential biases and confounding variables, proper statistical control will be applied and therefore it is expected that the results will be applicable to the general population.

It is expected that the final target dosage will be with the 10 or 15 mg group. This is based on knowledge gained by the rat studies conducted earlier.

This study will be considered preliminary as far as determining dosages as far as clinical applications are concerned. After this study a formal study to determine conclusively that the dosage determined to the be optimal dose is effective in lowering serum cholesterol in human beings. No marketing claims can be made based on this study and will have to wait until further testing is conducted. This study is necessary and further testing cannot be conducted until it is completed. Preliminary results based on studies conducted on laboratory rats look promising as far as expected results of this study are concerned.

This study is only the next step in the development of the final product for marketing to clinicians and usage on the general public. Cholesterease is expected to be a product in high demand and fills a niche in the market that is not currently be addressed. Cholesterease solves many of the problems associated with competitor products and has no competition in Great Britain. The elimination of side effects associated with competitor products is expected to be a key selling point that will put Cholesterease ahead of its competition.

End Notes

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Manson, J. et al., (1992)The primary prevention of myocardial infarction. N. Eng. J. Med.

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Kronmal, R. et al. (1993) Total Serum Cholesterol Levels and Mortality Risk as a function of Age, A report based on the Framingham Data. Arch. Intern. Med 153 p.1065-1073.

Hudson, M.(2003) How Cholesterol Affects the Body. BurnBraeFarms.com. (Online at (http://www.burnbraefarms.com/nutrition/cholesterolnews.pdf) Accessed June 4, 2003.

Parker-Pope, T.(2002) Cholesterol Drug Raises Questions About Side Effects. Wall Street

Journal. February 1, 2002.

Howell, W. et al. (1997) Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis. Am. J. Clin. Nutr. 65 p. 1747-1764.

Otani H, et. al. (1992) Long-term effects of a cholesterol-free diet on serum cholesterol levels in Zen monks. New England Journal of Medicine. P. 326:416.

Clarke, R. et al. (1997) Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. Brit. Med. Journal 314 p.112-117.

Rozzini, R. et al., (1996) Low serum cholesterol and serotonin metabolism. Risk of depression is higher in elderly patients with lowest cholesterol values. Brittish Medical Journal 312 (7041) p. 1298-1299.

Howell, W. et al. (1997) Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis. Am. J. Clin. Nutr. 65 p.1747-1764.