CLINICAL TRIALS CTR



Researcher : Chow LWC
Project Title:Chemosensitivity study using a breast cancer cell line
Investigator(s):Chow LWC
Department:Surgery
Source(s) of Funding:Other Funding Scheme
Start Date:05/1996
Abstract:
To test the effect of combination chemotherapy on cell growth in a breast cancer cell line.


List of Research Outputs

Loo T...Y...W..., Jin L.J., Cheung N.B.M. and Chow L.W.C., Evaluation of Ellagic acid on the activities of oral bacteria with the use of adenosine triphosphate (ATP) bioluminescence assay, African Journal of Biotechnology. 2010, 9: 3938-3943.
Loo T.Y.W., Jin L.J., Cheung N.B.M., Chow L.W.C. and Wang M., Combination of radiological and biochemical methods to assess bone mineral density of mandible in fully edentulous patients after chemotherapy: a 5-year prospective study, Expert Opinion on Investigational Drugs. 2010, 19 (Suppl 1): S109-S115.
Loo T.Y.W., Jin L.J., Chow L.W.C., Cheung M.N.B. and Wang M., Rhodiola algida improves chemotherapy-induced oral mucositis in breast cancer patients, Expert Opinion on Investigational Drugs. 2010, 19 (Suppl 1): S91-S100.


Researcher : Karlberg JPE
List of Research Outputs

Karlberg J.P.E., Yau K.C., Goh P...P..., Ong L...M..., Loh C...S... and Lim T...O..., A Case study: Refining Clinical Research Infrastructure, Clinical Trial Magnifier. 2010, 3(3): 203-218.
Karlberg J.P.E., Biomedical Publication Trends by Geographic Area, Clinical Trial Magnifier. 2010, 2(12): 682-701.
Karlberg J.P.E., Building Trust in Multi-Regional Clinical Trials (MRCTs), Pfizer Multi-Regional Clinical Trial Summit Meeting at the Harvard Faculty Club, New York, US, 19-20 January 2010.. 2010.
Karlberg J.P.E., CRA Megatrend Workshop organized by the Government of Saudi Arabia, Singapore, 7 October 2009. 2009.
Karlberg J.P.E., China: Reviewing crucial regulatory considerations, Informa Life Sciences’ 4th Annual Clinical Trials in Emerging Economies 2010, Brussels, Belgium, 29-30 June 2010. 2010.
Karlberg J.P.E., Clinical Research Accreditation, Clinical Trial Magnifier. 2009, 2(7): 361-372.
Karlberg J.P.E., Clinical Research Motivation, Clinical Trial Magnifier. 2010, 3(2): 72-75.
Karlberg J.P.E. and Yau K.C., Clinical Research Organization Infrastructure, Clinical Trial Magnifier. 2010, 3(2): 76-103.
Karlberg J.P.E., Clinical Trial Subject Characteristics - Ages and Gender, Clinical Trial Magnifier. 2009, 2(9): 456-471.
Karlberg J.P.E., Educating IRB Members, Clinical Trial Magnifier 2009 Conference, Hong Kong, 13-15 November 2009. 2009.
Karlberg J.P.E., Enhancing the Quality and Efficiency of Ethical Review, Clinical Trial Magnifier. 2010, 3(1): 12.
Karlberg J.P.E., Global Trends in multi-national Clinical Trials, KBIO-WCK Joint Seminar on Global Trends of Clinical Trial for Biological Drugs, Seoul, Korea, 25-26 May 2010. 2010.
Karlberg J.P.E., Globalization in Human Research Ethics: Today and for the Future, National Conference organized by Canadian National Council on Ethics in Human Research (NCEHR), Ottawa, Canada, 20-21 February 2010. 2010.
Karlberg J.P.E., Globalization of Clinical Research and Accreditation, World Courier Webinar, Hong Kong, 21 April 2010. 2010.
Karlberg J.P.E., Globalization of Clinical Trials - Trends, Effects and Significances, National Conference for Clinical Research 2009, Penang, Malaysia, 9 July 2009. 2009.
Karlberg J.P.E., Globalization of Clinical Trials – Trends, Effects & Significance, World Courier’s Lunch Seminar: Globalization of Clinical Trials and The Role of Hong Kong in Global Drug Development, Hong Kong, China, 25 August 2009. 2009.
Karlberg J.P.E., ICP Growth Model, Pfizer Global Pharmaceuticals: Child Growth Research Workshop Presentation, Stockholm, Sweden, 6-7 May 2010. 2010.
Karlberg J.P.E., Industry Sponsored Medical Device Clinical Trials, Clinical Trial Magnifier. 2009, 2(7): 348-360.
Karlberg J.P.E., Yao T.J. and Yau K.C., Industry Sponsored Oncology Clinical Trials, Clinical Trial Magnifier. 2009, 2(8): 402-416.
Karlberg J.P.E. and Yau K.C., Magnifier Subscriber Survey - Study Site Location Selection Criteria, Clinical Trial Magnifier. 2009, 2(9): 475-488.
Karlberg J.P.E., Magnifier Subscriber Survey - The Ethics Guide, Clinical Trial Magnifier. 2010, 3(3): 220-230.
Karlberg J.P.E., Office of Human Protection Assurance, Clinical Trial Magnifier. 2009, 2(8): 418-424.
Karlberg J.P.E., Overview of Major Ongoing Clinical Trials in Solid Tumors in Asia Pacific, Asia Pacific Advisory Conference on Solid Tumors, Taipei, Taiwan, 22 May 2010. 2010.
Karlberg J.P.E., Overview of clinical trials in Asia and Hong Kong Clinical Trials Centre experiences, The 9th Thailand Towards Excellence in Clinical Trials Forum 2009, Bangkok, Thailand, 20-21 August 2009. 2009.
Karlberg J.P.E. and Speers M...A..., Reviewing Clinical Trials: A Guide for the Ethics Committee. 2010, 1-160.
Karlberg J.P.E., Setting up Clinical Research Center, Pre-conference seminar of The 9th Thiland Towards Excellence in Clinical Trials Forum 2009, Bangkok, Thailand, 19 August 2009. 2009.
Karlberg J.P.E. and Tam S.Y.M., Standard Operating Procedures - a Trust and not a Must, Clinical Trial Magnifier. 2010, 3(1): 33-35.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P5: Review of Case Report Form (CRF), Clinical Trial Magnifier. 2009, 2(7): 377-378.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T1: Initiation Visit, Clinical Trial Magnifier. 2009, 2(12): 702-706.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P10: Pre-study Planning for Laboratory Investigations, Clinical Trial Magnifier. 2009, 2(9): 491-493.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P6: Study Organisation and Planning, Clinical Trial Magnifier. 2009, 2(7): 379-382.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P11: Investigators' Meeting and Good Clinical Practice Training, Clinical Trial Magnifier. 2009, 2(11): 652-653.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P12: Application for Review by Institutional Review Board and Obtaining Approval, Clinical Trial Magnifier. 2009, 2(11): 654-656.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P13: Regulatory Authority Applications and Documents, Clinical Trial Magnifier. 2010, 3(3) - Annex XIII: 1-3.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P14: Vulnerable Subjects, Clinical Trial Magnifier. 2010, 3(3) - Annex XIV: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P7: Study Team: Definition of Responsibilities, Clinical Trial Magnifier. 2009, 2(8): 425-426.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P8: Recruitment of Subjects, Clinical Trial Magnifier. 2009, 2(8): 427-428.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P9: Pre-study Planning of Investigational Products, Clinical Trial Magnifier. 2009, 2(9): 489-490.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA10: Conflict of Interest Resolution, Clinical Trial Magnifier. 2010, 3(3) - Annex X: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA11: Feasibility Study, Clinical Trial Magnifier. 2010, 3(3) - Annex XI: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA12: Dissemination of Study Results, Clinical Trial Magnifier. 2010, 3(3) - Annex XII: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA1: Study-Specific Audit, Clinical Trial Magnifier. 2010, 3(3) - Annex I: 1-46.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA2: Study-Specific Inspection, Clinical Trial Magnifier. 2010, 3(3) - Annex II: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA3: Preparation, Approval, Review and Maintenance of SOPs, Clinical Trial Magnifier. 2010, 3(3) - Annex III: 1-4.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA4: Human Research Protection Program, Clinical Trial Magnifier. 2010, 3(3) - Annex IV: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA5: Fraud and Misconduct, Clinical Trial Magnifier. 2010, 3(3) - Annex V: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA6: Confidentiality Agreement, Obligations and Practices, Clinical Trial Magnifier. 2010, 3(3) - Annex VI: 1-4.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA7: Participant’s Complains, Clinical Trial Magnifier. 2010, 3(3) - Annex VII: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA8: Emergency Resuscitation – Cardiac Arrest, Clinical Trial Magnifier. 2010, 3(3) - Annex VIII: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA9: Trial Registry, Clinical Trial Magnifier. 2010, 3(3) - Annex XI: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S1: Site Description, Clinical Trial Magnifier. 2010, 3(2): 119-124.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S2: Staff CV, Clinical Trial Magnifier. 2010, 3(2): 125-126.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S3: Staff Responsibilities, Duties and Job Descriptions, Clinical Trial Magnifier. 2010, 3(2): 127-128.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S4: Staff Education and Documentation, Clinical Trial Magnifier. 2010, 3(2): 129-131.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S5: Induction Programme For New Employees, Clinical Trial Magnifier. 2010, 3(2): 132-134.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S6: Staff Communication Principles, Clinical Trial Magnifier. 2010, 3(2): 135-137.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S7: Staff Reviews, Clinical Trial Magnifier. 2010, 3(2): 138-140.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S8: Staff Meetings, Clinical Trial Magnifier. 2010, 3(2): 141.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T10: Monitoring Visit, Clinical Trial Magnifier. 2010, 3(2): 155-159.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T2: Subject Recruitment to Enrollment, Clinical Trial Magnifier. 2009, 2(12): 707-710.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T3: Obtaining Written Informed Consent, Clinical Trial Magnifier. 2010, 3(1): 36-40.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T4: Investigational Products Accounting, Dispensing and Administration, Clinical Trial Magnifier. 2010, 3(1): 41-45.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T5: Blinding: Codes And Code Breaking, Clinical Trial Magnifier. 2010, 3(1): 46-47.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T7: Remote Data Capture, Clinical Trial Magnifier. 2010, 3(2): 142-145.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T8: Data Clarification, Clinical Trial Magnifier. 2010, 3(2): 146-149.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T9: Randomization, Clinical Trial Magnifier. 2010, 3(2): 150-154.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure: SOP T6: Paper Case Report Form Completion, Clinical Trial Magnifier. 2010, 3(1): 48-49.
Karlberg J.P.E., What is hidden in snow may appear at thaw, Clinical Trial Magnifier. 2010, 3(1): 3-5.


Researcher : Tam S
List of Research Outputs

Dai Y.L., Luk T.H., Siu D.C.W., Yiu K.H., Chan K.H.T., Lee S.W.L., Li S.W., Fong B., Wong W.K., Tam S., Lau C.P. and Tse H.F., Mitochondrial dysfunction induced by statin contributes to endothelial dysfunction in patients with coronary artery disease., Cardiovascular Toxicology. 2010, 10: 130-8.


Researcher : Tam SYM
List of Research Outputs

Karlberg J.P.E. and Tam S.Y.M., Standard Operating Procedures - a Trust and not a Must, Clinical Trial Magnifier. 2010, 3(1): 33-35.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P5: Review of Case Report Form (CRF), Clinical Trial Magnifier. 2009, 2(7): 377-378.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T1: Initiation Visit, Clinical Trial Magnifier. 2009, 2(12): 702-706.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P10: Pre-study Planning for Laboratory Investigations, Clinical Trial Magnifier. 2009, 2(9): 491-493.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P6: Study Organisation and Planning, Clinical Trial Magnifier. 2009, 2(7): 379-382.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P11: Investigators' Meeting and Good Clinical Practice Training, Clinical Trial Magnifier. 2009, 2(11): 652-653.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P12: Application for Review by Institutional Review Board and Obtaining Approval, Clinical Trial Magnifier. 2009, 2(11): 654-656.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P13: Regulatory Authority Applications and Documents, Clinical Trial Magnifier. 2010, 3(3) - Annex XIII: 1-3.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P14: Vulnerable Subjects, Clinical Trial Magnifier. 2010, 3(3) - Annex XIV: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P7: Study Team: Definition of Responsibilities, Clinical Trial Magnifier. 2009, 2(8): 425-426.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P8: Recruitment of Subjects, Clinical Trial Magnifier. 2009, 2(8): 427-428.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP P9: Pre-study Planning of Investigational Products, Clinical Trial Magnifier. 2009, 2(9): 489-490.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA10: Conflict of Interest Resolution, Clinical Trial Magnifier. 2010, 3(3) - Annex X: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA11: Feasibility Study, Clinical Trial Magnifier. 2010, 3(3) - Annex XI: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA12: Dissemination of Study Results, Clinical Trial Magnifier. 2010, 3(3) - Annex XII: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA1: Study-Specific Audit, Clinical Trial Magnifier. 2010, 3(3) - Annex I: 1-46.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA2: Study-Specific Inspection, Clinical Trial Magnifier. 2010, 3(3) - Annex II: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA3: Preparation, Approval, Review and Maintenance of SOPs, Clinical Trial Magnifier. 2010, 3(3) - Annex III: 1-4.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA4: Human Research Protection Program, Clinical Trial Magnifier. 2010, 3(3) - Annex IV: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA5: Fraud and Misconduct, Clinical Trial Magnifier. 2010, 3(3) - Annex V: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA6: Confidentiality Agreement, Obligations and Practices, Clinical Trial Magnifier. 2010, 3(3) - Annex VI: 1-4.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA7: Participant’s Complains, Clinical Trial Magnifier. 2010, 3(3) - Annex VII: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA8: Emergency Resuscitation – Cardiac Arrest, Clinical Trial Magnifier. 2010, 3(3) - Annex VIII: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP QA9: Trial Registry, Clinical Trial Magnifier. 2010, 3(3) - Annex XI: 1-2.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S1: Site Description, Clinical Trial Magnifier. 2010, 3(2): 119-124.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S2: Staff CV, Clinical Trial Magnifier. 2010, 3(2): 125-126.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S3: Staff Responsibilities, Duties and Job Descriptions, Clinical Trial Magnifier. 2010, 3(2): 127-128.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S4: Staff Education and Documentation, Clinical Trial Magnifier. 2010, 3(2): 129-131.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S5: Induction Programme For New Employees, Clinical Trial Magnifier. 2010, 3(2): 132-134.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S6: Staff Communication Principles, Clinical Trial Magnifier. 2010, 3(2): 135-137.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S7: Staff Reviews, Clinical Trial Magnifier. 2010, 3(2): 138-140.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP S8: Staff Meetings, Clinical Trial Magnifier. 2010, 3(2): 141.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T10: Monitoring Visit, Clinical Trial Magnifier. 2010, 3(2): 155-159.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T2: Subject Recruitment to Enrollment, Clinical Trial Magnifier. 2009, 2(12): 707-710.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T3: Obtaining Written Informed Consent, Clinical Trial Magnifier. 2010, 3(1): 36-40.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T4: Investigational Products Accounting, Dispensing and Administration, Clinical Trial Magnifier. 2010, 3(1): 41-45.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T5: Blinding: Codes And Code Breaking, Clinical Trial Magnifier. 2010, 3(1): 46-47.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T7: Remote Data Capture, Clinical Trial Magnifier. 2010, 3(2): 142-145.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T8: Data Clarification, Clinical Trial Magnifier. 2010, 3(2): 146-149.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure SOP T9: Randomization, Clinical Trial Magnifier. 2010, 3(2): 150-154.
Karlberg J.P.E. and Tam S.Y.M., Study Site Standard Operating Procedure: SOP T6: Paper Case Report Form Completion, Clinical Trial Magnifier. 2010, 3(1): 48-49.


Researcher : Tso AWK
Project Title:A population-based prospective study to investigate the associations of obesity and adipokines with the incidence of cardiovascular disease and cancer
Investigator(s):Tso AWK, Cheung BMY, Lam KSL, Lam TH, Lo SV, Tse HF, Wat NMS
Department:Medicine
Source(s) of Funding:Health and Health Services Research Fund - Full Grants
Start Date:12/2008
Abstract:
To investigate the associations of obesity indices, insulin resistance index and adipokines with the incidence of (1) cardiovascular disease and (2) cancer in a community-based prospectively followed-up cohort in Hong Kong.


Project Title:Adipocyte fatty acid-binding protein – an adipocytokine with a role in diabetic nephropathy ?
Investigator(s):Tso AWK, Lam KSL, Chan DTM, Xu A
Department:Medicine
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:06/2009
Abstract:
Adipocyte fatty acid-binding protein (A-FABP) belongs to a family of small cytoplasmic proteins important in mediating intracellular fatty-acid trafficking and energy metabolism. It is expressed predominantly in adipocytes but is also found in macrophages. A-FABP has been shown to influence various metabolic and inflammatory pathways. In mice, deletion of the A-FABP gene (aP2-/-) is associated with partial protection against glucose and lipid dysregulation in genetic and diet-induced obesity models1,2. An oral selective competitive inhibitor of A-FABP, BMS309403, has also been developed3, and treatment with BMS309403 led to significant improvement in glucose intolerance, insulin resistance and fatty infiltration of the liver in obese leptin-deficient mice3. At the cellular level, inhibition of A-FABP was associated with significant suppression of c-jun N-terminal kinase-1 (JNK) activity in adipose tissue and liver, resulting in improved insulin-stimulated tyrosine and Akt phosphorylation, and hence enhanced insulin signaling3. Furthermore, A-FABP is also likely to have pro-inflammatory effects. Macrophages from aP2-/- mice had reduced NFkB activity and reduced expression of inflammatory cytokines, such as tumour necrosis factor-, monocyte chemoattractant protein (MCP-1), interleukin-6 (IL-6) and interleukin-1(IL-1)4, as well as suppression of inducible nitric oxide synthase and cyclo-oxygenase 2 pathways5. In humans, we found that A-FABP is released into the circulation, and A-FABP levels were predictive of the development of type 2 diabetes6 and the metabolic syndrome7. Recently, in a cohort of patients with type 2 diabetes, we found that serum A-FABP level was significantly associated with the severity of diabetic nephropathy, and correlated positively with albumin excretion rate and serum creatinine but negatively with glomerular filtration rate8. Serum A-FABP level was independently associated with the presence of microalbuminuria and macroalbuminuria independent of age, sex, hypertension, waist circumference and LDL cholesterol8. However, whether A-FABP plays a direct role in the pathogenesis of diabetic nephropathy remains to be elucidated. Diabetic nephropathy is characterized by the progressive development of albuminuria, initially associated with glomerular hyperfiltration, followed by progressive decline in glomerular function. Histologically, there is thickening of glomerular basement membrane, mesangial expansion, glomerulosclerosis, tubulo-interstitial fibrosis and tubular atrophy. There is significant monocyte/ macrophage infiltration9, and inflammatory stress has been suggested to play an important role in the pathogenesis of diabetic nephropathy. In support of this, it has been found that progressive diabetic nephropathy is associated with increased NFkB and JNK10 activation, increased production of MCP-111 and tumour growth factor-1 (TGF1)12, and increasing macrophage accumulation parallels the development of renal injury and fibrosis10,13. On the other hand, suppression of macrophage infiltration, either by genetic or immunosuppressive approaches, significantly reduced the severity of diabetic nephropathy14. A-FABP is expressed in macrophages, and may modulate their pro-inflammatory cytokine productions4. In atherosclerosis-prone apolipoprotein-E-deficient mice, macrophage-restricted ablation of A-FABP resulted in significant reduction in atherosclerotic lesions, regardless of its expressions in adipocytes, suggesting that macrophage A-FABP plays a direct role in the pathogenesis in atherosclerosis4,15. Whether A-FABP released from macrophages may have a similar pathogenic role in diabetic nephropathy remains unknown. In this project, we propose to examine the relevance of A-FABP in the pathogenesis of diabetic renal disease in mice in both type 1 and type 2 diabetic mouse models: (1)Type 1 diabetes model: streptozotocin-induced diabetes, comparing the progression of nephropathy in A-FABP knockout mice with their wild-type littermate as controls. (2)Type 2 diabetes model: KK-Ay mice (a model of type 2 diabetes with spontaneous development of progressive albuminuria and nephropathy) will be used, and the effects of the administration of A-FABP inhibitor, BMS309403, on the progression of nephropathy as well as reversal of established nephropathy as compared to vehicle will be examined. Objectives To investigate the effects of 1. the genetic deletion of A-FABP in type 1 diabetes mouse model, and 2. the use of a selective inhibitor of A-FABP in type 2 diabetes mouse model on diabetic nephropathy, in particular looking for: A) progressive albuminuria B) macrophage infiltration and pro-inflammatory cytokine productions in kidneys C) histological changes associated with diabetic nephropathy.


List of Research Outputs

Ong K.L., Tso A.W.K., Leung Y.K., Cherny S.S., Sham P.C., Cheung B.M.Y. and Lam K.S.L., Relationship of genetic variants in gene encoding adrenomedullin with hypertension and dysglycaemia in Hong Kong Chinese, 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine, Co-morbidity Hypertension / Diabetes: which one do we treat, Dec 2009, Hong Kong. 2009.


Researcher : Yao T
Project Title:Sample Size Considerations in Comparative Clinical Trials with Time-to-Event Endpoints
Investigator(s):Yao TJ
Department:Clinical Trials Ctr
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:02/2008
Completion Date:02/2010
Abstract:
1. To study the efficiency of the targeted design in controlled clinical trials relative to the standard non-targeted trials with boarder eligibility criteria using time-to-event outcome as the primary endpoint In many medical applications, only a subset of patients may respond to an experimental treatment, with the rest of patients remain the same as those in the control group. It is recognized that the efficacy and toxicity of drugs are influenced by the genetically determined levels of drug-metabolizing enzymes and receptor levels [1]. In cancer management, for example, DNA changes in cancer cells are being used to diagnose risk of disease, early detection, prognosis and therapeutic response and disease recurrence [2]. Thus, clinical trials may be increasingly tailored for patients who are predicted to respond to therapy [3]. Genomics-based technologies make molecularly targeted treatment possible. We consider the design for controlled clinical trials where patients are randomized to receive either a new regimen E or a control regimen C. The potential trial patients will be screened and genetically typed. We assume that only a proportion of patients have certain specific gene signatures which predict response to the new treatment, and the rest patients do not have such signatures and are not predicted to be responsive. Only patients with the specified signatures are considered eligible in the targeted design. The eligible patients are then randomized and regimens E and C are compared within this subset. Since patient resources in a given disease category is limited, it is of interest to investigate whether the targeted design has better power in detecting the difference between the two treatments when compared to the standard randomized trial design where patients are not selected based on the specified gene signatures. Under similar considerations, Simon and Maitournam [4] and Maitournam and Simon [5] investigated the relative efficiency of the targeted trial design to the untargeted design for binary outcomes and for continuous outcomes, respectively. However, in many clinical trials, the most relevant endpoints have time-to-event data type. For example, in cancer trials where molecularly targeted treatments are considered very important strategies for disease management, the true, ultimate primary endpoint is time-to-progression or overall survival. We propose to study the relative efficiency of the targeted design to the un-targeted design for time-to-event outcomes given the same desired power; or the relative power given fixed number of available patients for screening. 2. To study the impact of delayed accrual and follow-up time on sample size and power for survival analysis For clinical trials with time-to-event endpoints, the logrank test is the most commonly used statistical procedure to compare differences between two treatment groups. Although this is a non-parametric test, distributional assumptions are necessary at the design stage; particularly, for the evaluation of sample sizes. The most common assumption is that time to event for the control group and that for the treatment group follow different exponential distributions with constant hazard rate over time. This approximation is reasonable for comparing curves with proportional hazards. This objective is motivated by trials with an accrual rate much slower than anticipated at design stage. In reality, time and resources for clinical trials are limited. We need to evaluate how long the trial may need and what is the minimal acceptable sample size with the actual accrual rate in order to determine whether to let the trial continue or stop. If it is plausible to speed up patient accruals, for example, by adding in additional study sites, we need to investigate how large an increase in accrual rate should be so that the study can be completed within an acceptable time frame. For time-to-event data, sample size determination is crucially dependent on the durations patients being followed. Apparently, the longer a patient is on study, the higher chance that the event occurs. The time that a patient stays on the study is affected by the study design and is equal to the time from enrollment to the end of the recruitment period plus the minimum follow-up time, if the patient does not drop-out before the study ends. Increasing minimum follow-up time is another approach to reduce the required sample size. We intend to investigate the inter-play between the accrual rate and the minimum follow up duration under different scenarios and provide recommendations when the accrual rate is realized to be slower than anticipated during the conduct of a randomized trial.


List of Research Outputs



Researcher : Yao TJ
Project Title:Sample Size Considerations in Comparative Clinical Trials with Time-to-Event Endpoints
Investigator(s):Yao TJ
Department:Clinical Trials Ctr
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:02/2008
Completion Date:02/2010
Abstract:
1. To study the efficiency of the targeted design in controlled clinical trials relative to the standard non-targeted trials with boarder eligibility criteria using time-to-event outcome as the primary endpoint In many medical applications, only a subset of patients may respond to an experimental treatment, with the rest of patients remain the same as those in the control group. It is recognized that the efficacy and toxicity of drugs are influenced by the genetically determined levels of drug-metabolizing enzymes and receptor levels [1]. In cancer management, for example, DNA changes in cancer cells are being used to diagnose risk of disease, early detection, prognosis and therapeutic response and disease recurrence [2]. Thus, clinical trials may be increasingly tailored for patients who are predicted to respond to therapy [3]. Genomics-based technologies make molecularly targeted treatment possible. We consider the design for controlled clinical trials where patients are randomized to receive either a new regimen E or a control regimen C. The potential trial patients will be screened and genetically typed. We assume that only a proportion of patients have certain specific gene signatures which predict response to the new treatment, and the rest patients do not have such signatures and are not predicted to be responsive. Only patients with the specified signatures are considered eligible in the targeted design. The eligible patients are then randomized and regimens E and C are compared within this subset. Since patient resources in a given disease category is limited, it is of interest to investigate whether the targeted design has better power in detecting the difference between the two treatments when compared to the standard randomized trial design where patients are not selected based on the specified gene signatures. Under similar considerations, Simon and Maitournam [4] and Maitournam and Simon [5] investigated the relative efficiency of the targeted trial design to the untargeted design for binary outcomes and for continuous outcomes, respectively. However, in many clinical trials, the most relevant endpoints have time-to-event data type. For example, in cancer trials where molecularly targeted treatments are considered very important strategies for disease management, the true, ultimate primary endpoint is time-to-progression or overall survival. We propose to study the relative efficiency of the targeted design to the un-targeted design for time-to-event outcomes given the same desired power; or the relative power given fixed number of available patients for screening. 2. To study the impact of delayed accrual and follow-up time on sample size and power for survival analysis For clinical trials with time-to-event endpoints, the logrank test is the most commonly used statistical procedure to compare differences between two treatment groups. Although this is a non-parametric test, distributional assumptions are necessary at the design stage; particularly, for the evaluation of sample sizes. The most common assumption is that time to event for the control group and that for the treatment group follow different exponential distributions with constant hazard rate over time. This approximation is reasonable for comparing curves with proportional hazards. This objective is motivated by trials with an accrual rate much slower than anticipated at design stage. In reality, time and resources for clinical trials are limited. We need to evaluate how long the trial may need and what is the minimal acceptable sample size with the actual accrual rate in order to determine whether to let the trial continue or stop. If it is plausible to speed up patient accruals, for example, by adding in additional study sites, we need to investigate how large an increase in accrual rate should be so that the study can be completed within an acceptable time frame. For time-to-event data, sample size determination is crucially dependent on the durations patients being followed. Apparently, the longer a patient is on study, the higher chance that the event occurs. The time that a patient stays on the study is affected by the study design and is equal to the time from enrollment to the end of the recruitment period plus the minimum follow-up time, if the patient does not drop-out before the study ends. Increasing minimum follow-up time is another approach to reduce the required sample size. We intend to investigate the inter-play between the accrual rate and the minimum follow up duration under different scenarios and provide recommendations when the accrual rate is realized to be slower than anticipated during the conduct of a randomized trial.


List of Research Outputs

Chan K.H., Yeung S.C., Yao T.J., Ip M.S.M., Cheung A.H.K., Chan M.M.W. and Mak J.C.W., Elevated Plasma Adiponectin Levels In Patients With Chronic Obstructive Pulmonary Disease, Hong Kong Medical Journal. 2010, 16 (Suppl. 1): 10.
Chen E.Y.H., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Pang E.P.F., Chan K.T., Wong Y.C., Mo F.Y.M., Chan K.P.M., Yao T.J., Hung S.F. and Honer W.G., Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial, British Medical Journal. 2010, 341: c4024.
Karlberg J.P.E., Yao T.J. and Yau K.C., Industry Sponsored Oncology Clinical Trials, Clinical Trial Magnifier. 2009, 2(8): 402-416.
Lam C.M., Lam B., Yao T.J., Lai A.Y.K., Ooi C.G.C., Tam S., Lam K.S.L. and Ip M.S.M., A randomized controlled trial of nCPAP on insulin sensitivity in obstructive sleep apnea, Eur Respir J. . 2009.
Lam C.M., Lam B., Yao T.J., Lai A.Y.K., Ooi C.G.C., Tam S., Lam K.S.L. and Ip M.S.M., A randomized controlled trial of nCPAP on insulin sensitivity in obstructive sleep apnea, European Respiratory Journal. 2010, 35(1): 138-145.
Mok T.M.Y., Yao T.J., Lo Y. and Tam S., Southern Chinese patients with systemic lupus erythematosus in Hong Kong have low vitamin D levels. , HKMJ. 2010, 16: p46 S77.
Tang S.C.W., Lam B., Yao T.J., Leung W.S., Chu C.M., Ho Y.W., Ip M.S.M. and Lai K.N., Sleep apnea is a novel risk predictor of cardiovascular morbidity and death in patients receiving peritoneal dialysis, Kidney International. 2010, 77(11): 1031-8.
Yau T.C.C., Yao T.J., Chan P., Epstein R., Ng K.K.C., Chok K.S.H., Cheung T.T., Fan S.T. and Poon R.T.P., The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolization, Cancer. 2009, 115(23): 5507-5515.


Researcher : Yau KC
List of Research Outputs

Karlberg J.P.E., Yau K.C., Goh P...P..., Ong L...M..., Loh C...S... and Lim T...O..., A Case study: Refining Clinical Research Infrastructure, Clinical Trial Magnifier. 2010, 3(3): 203-218.
Karlberg J.P.E. and Yau K.C., Clinical Research Organization Infrastructure, Clinical Trial Magnifier. 2010, 3(2): 76-103.
Karlberg J.P.E., Yao T.J. and Yau K.C., Industry Sponsored Oncology Clinical Trials, Clinical Trial Magnifier. 2009, 2(8): 402-416.
Karlberg J.P.E. and Yau K.C., Magnifier Subscriber Survey - Study Site Location Selection Criteria, Clinical Trial Magnifier. 2009, 2(9): 475-488.


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