Clinical Trails Human Subject Health And Social Care Essay

INTRODUCTION

The application of antigene therapy strategies such as Triplex forming oligonucleotide (TFO) has gained prominence use in the last few years. TFO has been used in antigene therapy, particularly as a site-specific mutation inducers and modulator of a gene expression (Guntaka, Varma and Weber, 2003; Frank-Kamenetskii, 1995). The ability to design a TFO that can recognize a unique site within mega-base segments of genomic DNA, offers a new approach to down regulate the expression of the target gene (Guntaka, Varma and Weber, 2003). Despite the success of the therapeutic application of TFO, there are still problems facing TFO development. Such problems include ability to design a TFO that can form a very stable hybrid with the target double DNA structures (Buchini and Leumann, 2003). Various TFOs has been developed in an attempt to overcome the poor hybrid stability of the complex formed by the TFO and target double DNA structures.

Studies show that the formation of complex by TFO with the target duplex DNA relies on Hoogsteen hydrogen bond formation (H.double DNA) that is largely restricted to adjacent polypurine DNA target sequences Buchini and Leumann, 2003; Sorensen, 2004).

Recent work has shown that pyridine-stretched analogue of 2-deoxyadenosine maintain the conventional Watson-Crick base pairing and forms a duplex structures with bonds that is more stable than the natural DNA (Buchini and Leumann, 2003)

AIM and OBJECTIVES

This project seeks to identify other pyridine-stretched analogue of 2-deoxyadenosine which are can form more stable complex with target duplex DNA structure. This new pyridine-stretched oligonucleotides (PSO) will be synthesise using existing routes and their interactions with different nucleic acid will be determined using different assay such as thermal stability test.

This phase of the project will focus only on the chemical synthesis and determination of the bond strength between the PSO and nucleic acid. Therefore, there is no need for in vitro testing of such analogues or further screening in vivo.

Hypothetical Extension

If potential highly stable analogues of pyridine-stretched oligonucleotide are discovered, these analogues will undergo further in-house screening. Any compound that is validated to be stable by the thermal stability test would be put forward into a series of toxicity trials, which will involve the usage of animals such as mice.

Compounds that are successful at this stage will be formulated with appropriate excipients and put forward for clinical trials in human subject. Due to the animal and human subject use, ethical issues of research are involved in the hypothetical extension to this project. Therefore, the research (hypothetical extension to this project) requires ethical review for the research ethics body.

Ethical Issues

Ethical Issues Raised by this Project

The ethical issues raised by this project include those concerning good scientific practice such as not manipulating the result or misconduct in the laboratory. Risk assessment and precautionary principle should be considered in other not to endanger one’s life. The research should not be conducted for personal benefits and must possess objectives (Mepham, 2008).

Ethical Issues Raised by the Hypothetical Extension to this Project

The specific ethical issues raised by the hypothetical extension of this project are those concerning the testing of potential compounds in animals and also in human clinical trails.

Animal Testing

The United Kingdom has one of the strictest animal acts that control the use of animals for scientific testing. The animal (Scientific procedures) Act of 1986 governed by the UK Government clearly defined the legal responsibilities of scientist whose research involves the use of animals (Mepham, 2008). Animal usage for experimental testing has raised different arguments over the years. A much wide spread argument is that benefits of medical research are greater than the overall harms to animals. However, the UK animal act stated clearly that the use of animals must be justified with a good argument about why alternatives to the animal testing cannot be use for the research work. At early stage in the design of the project, the three Rs principles should be put into consideration in order to minimise research impacts on animals use. These three Rs to follow include Reduction, Refinement and Replacement.

Reduction: Improving experimental techniques and data analysis techniques to minimise the numbers of animals (mice) use for testing should be encouraged by researchers.

Refinement: The experimental procedure should be refined in such a way that it can reduce suffering and distress to the mice. The ways animals can be care for to minimise distress include using less invasive techniques and better medical care and living conditions for the animals.

Replacement: Finding alternatives for experimental studies such as use of cell cultures instead of whole animals, computational techniques (molecular modelling), and the use of epidemiological studies to avoid the animal use (BBC).

The University ethics committee should be committed to ensure that the highest care standard and respect for the animals should be maintained.

Clinical Trails in Human Subject.

There are ethical considerations to the testing of the potential drug molecules for efficacy and toxicity in human. The human clinical trial should be design with greater transparency and the participant’s safety should be taken into consideration (Alisa, 2003). It is important to consider the Nuremberg Code prior to the clinical trials in human. The research should be scientifically sound with the main purpose of contributing to human health and knowledge (Mepham, 2008). The ethical issues related to the testing of the potential drug molecules in human include participant’s safety evaluation, informed consent of the participants and protection of the participant’s data (Salek and Edgar, 2002).

Safety Evaluation: The trail should be designed to avoid mental and physical suffering to the participants. The trial should not start or continue when there is probability that it can cause the death of the participants. Competent and fully qualified scientist should conduct the experiment. Risks to the human subjects should be of concern first before considering the interests of science (Salek and Edgar, 2002).

Informed Consent: Voluntary consent of the participants is essential in every research. Free and well informed consent of the participants should be obtained before their inclusion in the study (Alisa, 2003). The participants must be clearly and adequately informed in the language they understand about the experimental methodology, the anticipated outcome and potential risk of the study. In situation where the testing will take place in children, the consent of their legal guardian must be obtained. It is necessary to ensure that only competent people can participate in the study (Salek and Edgar, 2002).

Data Protection and Participants Right: The research should comply with Data Protection Act (1998) in relation to participant’s data usage and storage. The participants should have the right to opt out easily from the study whenever without explanation or penalty. Information provided by the participants should be treated as confidential and their identity should be protected (Salek and Edgar, 2002).

Ethical Approval

OBTAINING ETHICAL APPROVAL FROM ETHICAL COMMITTEE

Ethical approval from Research Ethics Committees (REC) is needed for the hypothetical extension of this project. Ethical review is designed by the REC to ensure that the research benefits do not come at the expense of abusing and exploiting the vulnerability of the study participants (Mepham, 2008). Approval of the study from REC is required to safeguard the researchers conducting the project and protect the safety, rights and the well being of participants of the study.

For research taking place in the university, Approval should be obtained from the university research ethics committee.

The following procedure should be followed for research ethics application in the United Kingdom:

Account creation on the online integrated research application system. The researcher should complete the online form and supply appropriate information about the project.

Slot booking with the REC after filling in the appropriate information in the online account system. A reference number will be issue after meeting with REC.

The assigned reference number will be filled in the appropriate section of the form.

Site-specific information should be filled along side the form for study that will take place in multiple sites.

Completed forms will be signed followed by submission of the appropriate documentations to REC.

The following documents will be sent to the research ethics office with some more mandatory than others:

Covering letter

Research ethics committee*

Site specific information form

Research protocol*

Investigator’s brochure or summary of product characteristics

Investigator’s curriculum vitae*

Participant information sheet*

Participant consent form*

Letter of invitation to participant

Information sheets or letters for general practitioners or consultants

Evidence of insurance or indemnity arrangements*

Letter from sponsor

Letter from statistician

Referees’ reports

Lay synopsis or flowchart of protocol

Details of any data monitoring committee

Sample diary card or patient card

Questionnaire

Interview schedules

Copies of recruitment advertisements, such as posters (Samjdor, et al., 2009).

In situation where the NHS patients will participate in the clinical trials, approval will be sought from NHS before conducting such trials. In addition to that, the participants consent form should be submitted along side with application form will be submitted to NHS research ethics committee for review (Clinpsy).