Genetic Factors Modulating Heroin Tolerance Capacity - Research Proposal Example

Summary of Research In reducing the physiological need for ‘heroin’, methadone serves as a treatment for heroin abuse. In line with this, it is necessary to determine the role of opioid receptors (i.e.,  and  ) in the establishment and the breakdown of tolerance since this information will enable forensic toxicologists to interpret blood drug concentrations of morphine, 6-monoacetylmorphine, and glucuronide metabolites after the use of heroin. Blood samples will be collected from the volunteers for lymphocyte preparation and DNA extraction purposes. By collecting blood samples from volunteers who are receiving methadone replacement therapy, this study aims to determine the role of opioid receptors (i.e. ,  and  ) that contributes to the mechanism of tolerance, drug resistance, and susceptibility to the drug. This study will benefit forensic toxicologists in enabling them offer a more meaningful interpretation of a blood drug concentration found in heroin abuse cases. This study will test the following hypothesis: (1) there is phenotypic inter-individual variation in the ability of UK population to maintain tolerance to heroin; (2) that this variation is a consequence of genetic polymorphism in opioid receptors; and (3) that individuals with specific genotypes have heightened sensitivity to modifying effects of methadone replacement therapy. In line with this, the following research objectives will be considered in testing the research hypothesis: (1) determine the extent of variation opioid receptors in heroin dependent volunteers who are receiving methadone therapy programme (0 – 9 months); (2) identify the functional consequences caused by genetic polymorphism (0 – 24 months); and (3) characterize the effects of methadone replacement therapy based on the levels of methadone replacement tolerance in each volunteer (0 – 36 months). To determine the extent of phenotypic variation in opioid receptors and identify common genetic polymorphisms, Europeans with history of heroin dependent that are currently undergoing methadone replacement therapy programme will be invited to participate in this study. To assess the contribution of methadone replacement in the patterns of opioid receptor expression, the researcher will re-measure the key receptor levels after the 6th week of methadone replacement period. Aside from identifying volunteers with responsive receptor to methadone replacement therapy, this approach will enable the researcher minimize the potential confounding effect of habitual lifestyle on phenotypically “high” and “low” expressers. Individuals with high or low levels of receptors and those with responsive phenotype will be classified under subgroups. Eventually, lymphocytes taken from the volunteers will be transformed using Epstein Barr Virus (EBV) to produce immortalized cell lines which will be use as a model system in studying the drug gene interactions that could modulate opiate receptor levels. Identification, Discussion of Ethical Issues, and Control of Ethical Issues Respect for Human Rights Among the common ethical issues that may happen when conducting a scientific-based research study includes matters that are related to the well-being of another person. As a common rule when conducting the actual research study, the researcher should respect the rights of another person by allowing them to make their own decision whether or not to participate in this study (Iltis, 2006, p. 126; Gregory, 2003, p. 41). In line with this, Israel and Hay (2006, p. 96) explained that harm caused by research activities is often “more likely to involve psychological distress, discomfort, social disadvantage, invasion of privacy or infringement of rights more than physical injury”. Iltis (2006, p. 139) stated that “disrespect occurs when researchers violate their subjects’ dignity, autonomy, or privacy”. For this reason, the researcher should at all times abide with the ethical norms associated with informed consent, autonomy, and confidentiality to avoid disrespecting another person or causing any form of physical or non-physical harm to the well-being of the qualified research volunteers. Given that the target research participants of this study includes the vulnerable group of people who are using heroin, there is a high risk that the research participants may not have fully understood the research study purpose and procedure at the time they agreed to participate in this study. As part of respecting the human rights of the research participants, the researcher should understand that the research participants can anytime decide whether or not to withdraw from participating in the research study. Without any questions asked, the researcher should respect and grant the research participants’ decision to withdraw from the research study anytime they want. Principle of Beneficence, Non-maleficence and Justice Aside from respecting human rights of other people, the researcher should always make ethically accepted decisions that are in accordance to the principle of beneficence, non-maleficence, and justice. Non-maleficence is about reducing the risk wherein the target research participants could encounter harm or discomfort during or after agreeing to participate in the research study whereas the principle of beneficence is all about promoting the well-being of the research participants by not exploiting them one way or the other (Israel and Hay, 2006, p. 95). Therefore, the researcher should always consider the welfare of the research participants before, during and after making important decisions on how to conduct the proposed primary research study. Justice is simply referring to the researcher’s obligation to be fair to all persons involved in this study. In case the researcher will encounter a qualified research participant who is less fortunate than the others, the researcher is obliged to treat each and every research participant equally regardless of age, gender, competence or socio-economic status in life (Israel and Hay, 2006. P. 36). To avoid actions that will cause harm to the research participants, the researcher should make sure that the part-time nurse will make use and immediately discard disposable syringe and needles right after collecting the blood samples of each research participant. Taking this into consideration will prevent the research participants from having the need to face the health consequences of blood-borne diseases. Normally, blood samples are taken through direct venipuncture. However, frequently repeated venipuncture could make the research respondents suffer from anxiety, discomfort, pain, and bruising at the puncture site. In line with this, Bonate and Howard (2004, p. 58) strongly suggest that indwelling arterial or venous catheter should be considered when there is a need for frequent blood sampling. With regards to the volume of blood sample, Bonate and Howard (2004, p. 58) revealed that “the maximum acceptable blood loss per subject is typically around 10% of circulating blood volume each week or approximately 500 mL or 50 – 80 mL per kilogram body weight”. Therefore, drawing 50mL of blood sample from the research participants is considered clinically safe. Autonomy and Informed Consent Autonomy is referring to the right of a person to make a personal choice whether or not to participate in a research study. Since the principle of informed consent requires each research participant to give their voluntary consent to participate in a research study (Gregory, 2003, p. 39), observing the ethical considerations behind informed consent is similar to respecting other people’s dignity and human right to decide. There are some cases wherein the research participants may end up feeling exploited by the researchers because they were not given to opportunity to know about the full details of the research plan before allowing them to decide whether or not to participate in the actual research study. In respect with the law of autonomy, the researcher is obliged to explain and provide the full information with regards to the purpose of this study including what will be required from the research participants. With regards to the purpose of this study, the researcher should inform the prospective research participants that their decision to join in this study will require them to allow the registered nurses to collect blood samples from them at least in three different occasions for the study to be successful. In line with this, the research participants should be properly informed that a part-time nurse will be assigned to collect 50 ml of their blood samples once a year for three consecutive years. Basically, the first batch of collected blood sample will be use to determine the opioid receptor levels and identify polymorphisms as the research participants receive methadone maintenance therapy. The second batch of collected blood sample will be use in determining the opioid receptor levels and identify high or low expressers and responders. The last batch of collected blood samples will be use in determining the lymphoblastoid cell lines before receiving modulation by methadone replacement therapy. (See Appendix I – Illustration of the Research Project Overview on page 11) Given that the prospective research participants for this study includes European individuals who are heroin users, there is a high risk that some of the prospective research participant may not be mentally in the position to give informed consent. In case the patient is not capable to decide whether or not to participate in the research study, it is ethical for the researcher to wait for another time before approaching the potential research participant to participate in this study (preferably when the patient is no longer high from the use of heroin). To ensure that the researcher will be able to address future enquiries or concerns of the research participants, the researcher will give them the option to call a 24-hour hotline wherein they will be given the opportunity to ask anything they want concerning this project. Law of Confidentiality The law of confidentiality requires the researcher to respect the privacy of the research participants by not disclosing their personal information or identity to the public or any third party (Israel and Hay, 2006, p. 78; Gregory, 2003, p. 49). During the research study period, the researcher will instruct the research assistant, the grade E technician and the nurse to strictly observe the law of confidentiality by not disclosing the research participants’ personal identity or information to anyone. Immediately after completing the research study, the researcher will keep the gathered data in a secured filing cabinet together with the hard and soft copy for a period of no more than five years. With regards to the final research study report, the researcher will intentionally not include any information that will directly or indirectly disclose the personal identity of the research participants. In line with this, the final research study report will not include the names of the research participants. Instead, the researcher will describe and interpret the research findings using a general analysis approach. Given that there is a need to disclose the research participants’ identity to other people, the researcher should seek approval directly from the person involved in the study. In case the research participant does not allow his identity to be known to the public, it is ethical on the part of the researcher to respect the research participants’ decision. Research Findings Analysis and Interpretation When analyzing and interpreting the gathered data from the primary research findings, it is unethical on the part of the researcher to manipulate the research findings (Shrader-Frechette, 1994, p. 86). Since the success of this study is highly dependent on the integration of human sample collection and laboratory work, the researcher will allocate 10% of his/her salary for travelling expenses and cost of two UK-based and one international conferences to facilitate dissemination of results. To complete this study, active participation of full-time research assistant with knowledge on molecular biology, part-time grade E technician with experience in handling and processing human biological samples and tissue culture, and part-time nurse is required. During the first two years, the research assistant will perform assays on opiate receptors and identify genotypic polymorphisms in genes. On the final year, the research assistant will perform the actual cell culture task. Justified Decision on Whether the Research Should get Ethical Clearance Given that this study was able to comply with the ethical concerns when conducting a science-based research proposal (i.e. respect for human rights, principles of beneficence, non-maleficence and justice, autonomy and informed consent, and law of confidentiality), it is safe to conclude that this study requires no further modifications and that the proposed research study information is sufficiently provided. For this reason, the University Research Ethics Committee will give the researcher the final approval to proceed with the research study. *** End *** Appendix I – Illustration of the Research Project Overview References Bonate, P., and Howard, D. (2004). Pharmacokinetics in drug development: Regulatory and development paradigms. American Association of Pharmaceutical Scientists. Gregory, I. (2003). Ethics in research. YHT Ltd. Iltis, A. (2006). Research ethics. Routledge Taylor & Francis Group. Israel, M., and Hay, I. (2006). Research ethics for social scientists. Sage Publications Ltd. Shrader-Frechette, K. (1994). Ethics of scientific research. Rowman & Littlefield Publishers Inc. Read More