A – Discuss the short-comings of the TGN1412 clinical trial?
B – Summarise the regulatory changes (in particular the EMEA CHMP Swp01 2007 guidelines) that were introduced following the TGN1412 incident and explain how then aim to reduce the risks of ‘first-in-man” trials.

Support your discussions with relevant peer-reviewed publications where appropriate and include a list of references.

Guidelines
Word limit is 2000 words (+/- 200 words) in total for Parts A & B combined.
Please include the total word count (excluding references) on the title page.
Example of referencing format below and please note policy on plagiarism.

Referencing:
For this assignment the Vancouver or Harvard style of referencing may be used.

As an example of the Vancouver Style of referencing, the references should be listed in a reference section at the end of the essay (not as footnotes), and should cited by number at the end of the sentence or paragraph to which they relate. Every statement of fact should be supported by a reference. If a whole section is derived from one reference, cite it at the end of the first and last sentence of the relevant section.
Authors, journal details, dates and article titles should all be given. Web sources should be cited giving the URL, the title, the authors, and the date last modified (where possible). The reference list at the end of the assignment should contain all the sources cited, listed numerically according to citation order, and be formatted according to the style shown overleaf.

Referencing example:
Substance P-enhanced endothelial cell proliferation and in vivo angiogenesis are mimicked by selective NK1 receptor agonists and inhibited by antagonists of neurokinin receptors (1,2). Substance P may also stimulate neurokinin-2 receptors (NK2) in some peripheral tissues, although it binds NK2 receptors with lower affinity than NK1 receptors (2,3). Specific, non-peptide antagonists of neurokinin receptors have been developed, of which SR140333 and SR144190 display high affinity, stereoselectivity, and receptor subtype specificity at rat NK1 and NK2 receptors, respectively (3,4,5).

References
1. Fan TP, Hu DE, Guard S, Gresham GA, Watling KJ. Stimulation of angiogenesis by substance P and interleukin-1 in the rat and its inhibition by NK1 or interleukin-1 receptor antagonists. Br J Pharmacol (1993) 110: 43–49.
2. Ziche M, Morbidelli L, Masini E, Amerini S, Granger HJ, Maggi CA, Geppetti P, Ledda F. Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Investig (1993) 94: 2036–2044.
3. Emonds-Alt X, Doutremepuich JD, Heaulme M, Neliat G, Santucci V, Steinberg R, Vilain P, Bichon D, Ducoux JP, Proietto V, et al. In vitro and in vivo biological activities of SR140333 , a novel potent non-peptide tachykinin NK1 receptor antagonist. Eur J Pharmacol (1993) 250: 403–413.
4. Oury-Donat F, Lefevre IA, Thurneyssen O, Gauthier T, Bordey A, Feltz P, Emonds-Alt X, Le Fur G, Soubrie P. SR 140333, a novel, selective and potent nonpeptide antagonist of the NK1 tachykinin receptor: characterization on the U373MG cell line. J Neurochem (1993) 62: 1399–1407.
5. Emonds-Alt X, Advenier C, Cognon C, Croci T, Daoui S, Ducoux JP, Landi M, Naline E, Neliat G, Poncelet M, et al. Biochemical and pharmacological activities of SR 144190, a new potent non-peptide tachykinin NK2 receptor antagonist. Neuropeptides (1993) 31: 449–458.
Referencing books or book chapters:

Brading AF. Ionic distribution and mechanisms of transmembrane ion movements in smooth muscle. In: Smooth Muscle: An Assessment of Current Knowledge. (1991) Bulbring E, Brading AF, Jones AW and Tomita T, Eds. pp. 65–92. Edward Arnold Press, London.
Referencing web materials is more troublesome than print copy. Here is the suggested format (date last accessed in parentheses). Where some details are not available, include as much of the information as possible:

1. N Osterweil. Statin Therapy Effective for Primary Prevention of CVD, Stroke in Diabetics. Medscape Medical News 2004. http://www.medscape.com/viewarticle/480290 (20th July 2004), last modified July 2004.
2. Anonymous. Pravastatin: Clinical Pharmacology. RxList. http://www.rxlist.com/cgi/generic/pravast_cp.htm (21st July 2004)
Plagarism:
Students are reminded that copying other people’s work (including text, figures or tables) without citing the source and author is plagiarism, a form of cheating. The assignment should be phrased in your own words and should result from your own intellectual input. Students that do not credit the source of their information, or who acquire parts or the entirety of their assignment from a contracted/commercial agent, or who copy significant sections of work verbatim from other sources (even if the source is cited), will receive no marks.

Plagiarism is defined as follows:
Plagiarism is the use of other people’s work in an assignment and presenting it as your own without explicitly acknowledging – or referencing – where it came from. Plagiarism can also mean not acknowledging the full extent of indebtedness to a source. Work can be plagiarized from many sources – including books, articles, the internet, and other students’ assignments. Plagiarism can easily occur unconsciously or inadvertently. Direct copying is also plagiarism. Paraphrasing of other work without attribution is also plagiarism. Submitting someone else’s unattributed or less than fully attributed work or ideas is not evidence of your own grasp of the material and cannot earn you marks.

A – Discuss the short-comings of the TGN1412 clinical trial?
B – Summarise the regulatory changes (in particular the EMEA CHMP SWP 2007 guidelines) that were introduced following the TGN1412 incident and explain how then aim to reduce the risks of ‘first-in-man” trials.

Support your discussions with relevant peer-reviewed publications where appropriate and include a list of references.

Guidelines
Word limit is 2000 words (+/- 200 words) in total for Parts A & B combined.
Please include the total word count (excluding references) on the title page.
Example of referencing format below and please note policy on plagiarism.

Referencing:
For this assignment the Vancouver or Harvard style of referencing may be used.

As an example of the Vancouver Style of referencing, the references should be listed in a reference section at the end of the essay (not as footnotes), and should cited by number at the end of the sentence or paragraph to which they relate. Every statement of fact should be supported by a reference. If a whole section is derived from one reference, cite it at the end of the first and last sentence of the relevant section.
Authors, journal details, dates and article titles should all be given. Web sources should be cited giving the URL, the title, the authors, and the date last modified (where possible). The reference list at the end of the assignment should contain all the sources cited, listed numerically according to citation order, and be formatted according to the style shown overleaf.

Referencing example:
Substance P-enhanced endothelial cell proliferation and in vivo angiogenesis are mimicked by selective NK1 receptor agonists and inhibited by antagonists of neurokinin receptors (1,2). Substance P may also stimulate neurokinin-2 receptors (NK2) in some peripheral tissues, although it binds NK2 receptors with lower affinity than NK1 receptors (2,3). Specific, non-peptide antagonists of neurokinin receptors have been developed, of which SR140333 and SR144190 display high affinity, stereoselectivity, and receptor subtype specificity at rat NK1 and NK2 receptors, respectively (3,4,5).

References
1. Fan TP, Hu DE, Guard S, Gresham GA, Watling KJ. Stimulation of angiogenesis by substance P and interleukin-1 in the rat and its inhibition by NK1 or interleukin-1 receptor antagonists. Br J Pharmacol (1993) 110: 43–49.
2. Ziche M, Morbidelli L, Masini E, Amerini S, Granger HJ, Maggi CA, Geppetti P, Ledda F. Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Investig (1993) 94: 2036–2044.
3. Emonds-Alt X, Doutremepuich JD, Heaulme M, Neliat G, Santucci V, Steinberg R, Vilain P, Bichon D, Ducoux JP, Proietto V, et al. In vitro and in vivo biological activities of SR140333 , a novel potent non-peptide tachykinin NK1 receptor antagonist. Eur J Pharmacol (1993) 250: 403–413.
4. Oury-Donat F, Lefevre IA, Thurneyssen O, Gauthier T, Bordey A, Feltz P, Emonds-Alt X, Le Fur G, Soubrie P. SR 140333, a novel, selective and potent nonpeptide antagonist of the NK1 tachykinin receptor: characterization on the U373MG cell line. J Neurochem (1993) 62: 1399–1407.
5. Emonds-Alt X, Advenier C, Cognon C, Croci T, Daoui S, Ducoux JP, Landi M, Naline E, Neliat G, Poncelet M, et al. Biochemical and pharmacological activities of SR 144190, a new potent non-peptide tachykinin NK2 receptor antagonist. Neuropeptides (1993) 31: 449–458.
Referencing books or book chapters:

Brading AF. Ionic distribution and mechanisms of transmembrane ion movements in smooth muscle. In: Smooth Muscle: An Assessment of Current Knowledge. (1991) Bulbring E, Brading AF, Jones AW and Tomita T, Eds. pp. 65–92. Edward Arnold Press, London.
Referencing web materials is more troublesome than print copy. Here is the suggested format (date last accessed in parentheses). Where some details are not available, include as much of the information as possible:

1. N Osterweil. Statin Therapy Effective for Primary Prevention of CVD, Stroke in Diabetics. Medscape Medical News 2004. http://www.medscape.com/viewarticle/480290 (20th July 2004), last modified July 2004.
2. Anonymous. Pravastatin: Clinical Pharmacology. RxList. http://www.rxlist.com/cgi/generic/pravast_cp.htm (21st July 2004)
Plagarism:
Students are reminded that copying other people’s work (including text, figures or tables) without citing the source and author is plagiarism, a form of cheating. The assignment should be phrased in your own words and should result from your own intellectual input. Students that do not credit the source of their information, or who acquire parts or the entirety of their assignment from a contracted/commercial agent, or who copy significant sections of work verbatim from other sources (even if the source is cited), will receive no marks.

Plagiarism is defined as follows:
Plagiarism is the use of other people’s work in an assignment and presenting it as your own without explicitly acknowledging – or referencing – where it came from. Plagiarism can also mean not acknowledging the full extent of indebtedness to a source. Work can be plagiarized from many sources – including books, articles, the internet, and other students’ assignments. Plagiarism can easily occur unconsciously or inadvertently. Direct copying is also plagiarism. Paraphrasing of other work without attribution is also plagiarism. Submitting someone else’s unattributed or less than fully attributed work or ideas is not evidence of your own grasp of the material and cannot earn you marks.