Pharmacogenomics

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During the semi-structured interview the focus group participants were asked to complete a survey questionnaire, as outlined in Fig.1

Figure-1 Interview questionnaire[pic 1]

The responses from the interviewee were transcribed by three investigators and transcripts were elucidated by audio-visual recording.

Data Analysis:

The qualitative principle of content analysis was employed in this study to assess the obtained data. In this method, printed documentary data and responses gathered from the interviews was merged. Preliminary thematic framework was utilized to identify the key themes from the focus groups and the data was coded (Pope C, 2006). The severity of ADR reported from the focus groups was assessed by modified Hart wigs scale (Table 1) and the possibility of preventing the occurrence of such ADR was measured with modified Schumock-Thornton scale (Table 2). The Hap Map (Haplotype map) is a novel tool that permits researchers to identify interindividual genetic variations and gene build up that has considerable effects on health and susceptibility to develop devastating effect with administration of certain drugs. Sites in Deoxyribose Nucleic Acid (DNA) where variation at a single DNA base were referred to as Single Nucleotide Polymorphisms(SNPs). The specific pattern of SNP in a DNA block was referred to as Haplotype.

Hap Map was proved to be an effective resource for studying the contribution of genetic in determining the desired response and adverse responses to drugs. With the identification of SNPs, chromosome sites bearing varied haplotype patterns in the two focus groups of people, those who responds to therapy and those who does not respond were determined. Each and every chromosome region was studied extensively to locate the exact region of genetic variation that contribute to response. Thus, Hap Map usage led to development of tests in prediction of efficacy of drug in cancer patients with particular genotypes, for genes modified drug metabolism (P Deloukas and D Bentley, 2004).

Table-1 Hart wig’s Severity Assessment Scale

Level 1

An ADR occurred but required no change in treatment with the suspected

Level 2

The ADR required that treatment with the suspected drug be held, discontinued, or otherwise changed. No antidote or other treatment requirement was required. No increase in length of stay (LOS)

Leve 3

The ADR required that treatment with the suspected drug be held, discontinued, or otherwise changed. And/or an antidote or other treatment was required. No increase in length of stay (LOS)

Level 4

Any level 3 ADR which increases length of stay by at least 1 day or the ADR was the reason for the admission

Level 5

Any level 4 ADR which requires intensive medical care

Level 6

The adverse reaction caused permanent harm to the patient

Level 7

The adverse reaction either directly or indirectly led to the death of the patient

Mild= level 1 and 2, moderate= level 3 and 4, severe= 5, 6 and 7

Source: Srinivasan et al (2011)., International journal of research in pharmacy and chemistry.

Table-2 Modified Schumock and Thornton ADR preventability scale

Criteria determining the preventability of an ADR

Was the drug involved in the ADR not considered appropriate for the patient’s clinical condition?

Was the dose, route and frequency of administration not appropriate for the patient’s age, weight and disease state?

Was required therapeutic drug monitoring or other necessary laboratory test not performed?

Was there a history of allergy or previous reactions to the drug?

Was drug interaction involved in the reaction?

Was toxic serum drug level documented?

Was poor compliance involved in the reaction?

Source: Shumock GT, Thornton JP (1992), Focusing on the preventability of the ADR.

Results

Several adverse drug reactions were determined among the focus group which was tabulated below (Table 3), namely methotrexate, choice of therapy for Acute Lymphoid Leukemia(ALL), induced mucositis, leukoencephalitis and hair loss. Paclitaxel caused pancytopenia (decreased whole blood cell component) due to severe myelosuppression. Long term administration of carboplatin caused delayed puberty, infertility and gonadal dysfunction. cisplatin, first line chemotherapy for patients with brain tumor and osteosarcoma, was found to cause severe nephrotoxicity (kidney toxicity), ototoxicity (hearing loss) and sensory function impairment such as peripheral neuropathy.

Table-3 Percentage of ADR in the focus group

[pic 2]Source: Derived from VigiAccess database (www.vigiaccess.org).

The severity of the ADRs assessed by modified Hart wigs scale revealed majority of the ADRs that the patients in the focus group encountered was categorized under “moderate level”, followed by “mild” and “severe” level. The assessment form The Modified Schumock and Thornton scale, evaluated that few of the common ADR namely vomiting, hair loss and infection were “definitely preventable”, however the severe ADRs such as myelosuppression (bone marrow suppression), nephrotoxicity and infertility were “not preventable” by changes in the environmental factors. The non-preventable severe drug reactions were the sole cause in withdrawal of chemotherapy before stipulated time period. By adjusting the dose in compliance with the patient’s genetic base would bring about significant reduction in the non-preventable drug reactions.

Awareness of Personalized cancer