Catalyst Issue 12

JUL/AUG 2012 MICA (P) 243/03/2012NTU-NHG Infectious Conflict OfISG Awardees Diseases InterestPAGE 7 / RESEARCHERS FEATURE PAGE 16 / COLLABORATIONS PAGE 17 / EDUCATION IN RESEARCHEXCLUSIVE INTERVIEW ASSOCIATE PROFESSOR LEO YEE SIN

EDITORIAL workgroup from the editor in chief Health Services & Outcomes Dear Readers Research, NHG I thank you for your continued support to our NHG research newsletter – Catalyst. Charis Ng From this issue on, you will enjoy a richer scope and depth of contents with the recent formation of our first ever NHG Research Editorial Workgroup comprising of members from NHG institutions as well as our academic partner – Institute of Mental Health Nanyang Technological University. Teng Chiun How In this 2nd issue of Catalyst for 2012, we are honoured to have Associate Professor Leo Yee Sin, Head, Department of Infectious Diseases, Tan Tock Seng Hospital, and the recipient of the prestigious S$25 million Translational ClinicalNanyang Technological University Research (TCR) award for “STOP Dengue” share her insights on collaborative research in the cluster and beyond. Dr Anna Chan National Skin Centre Dr Mark Tang Veron Lu NHG Eye Institute This issue also features updates on the development of a vaccine by Inviragen for the Hand, Foot and Mouth DiseaseDr Augustinus Laude (HFMD) which remains prevalent amongst children in Singapore. We are also privileged to have Dr John Ovretveit from the Karolinska Institutet, Stockholm to share his thoughts on the importance of “Implementation Research” Dr Priti Minhas on healthcare. In addition, recipients of the National Medical Research Council (NMRC) Transition Award (TA) – Dr Jimmy Lee (Consultant, Institute of Mental Health (IMH)) shares on his journey as a Clinician Scientist in Psychiatry, NHG Polyclinics and Dr Ng Oon Tek (Consultant, Tan Tock Seng Hospital (TTSH)) brings us through his journey in Infectious Disease. Ann TohResearch & Development Office, NHG I would also like to take this opportunity to update that NHG has successfully launched 2 major grants this year. Chen Siya Launched in February 2012, the Clinician Scientist Career Scheme (CSCS) was aimed to develop a sizeable pool Clara Lim of Clinician Scientists in the cluster. To further develop the clusters’ research capabilities, NHG has also launched the NHG Thematic Grant on the 4th of July 2012. Each program is valued at S$1 million for over 3 years. We will Claudine Teo continue to keep you updated on our awardees in future issues of Catalyst. Stay tuned! Fanny Tandiono I hope you will enjoy reading this issue of Catalyst. Nonetheless, we are always happy to hear from you should you Farah Haniff have any suggestions for improvements. Kristen Guo Melody Teo ‘Till next time. Ng Hwee Hian Tay Lin Hwee Yours Sincerely, Tan Tock Seng Hospital Farah Dr Ng Oon Tek Noor Azizah Zainuldin Copyright © 2012 National Healthcare Group Pte LtdcontentsRESEARCHNEWS education regulations 19 Updates on Local Regulations03 Latest Research News 11 Qualité04 Research in Community 17 Responsible Conduct of Research money05 Research Services 18 Good Reference Book for Research 22 Local Grants/Awards Received06 Research Tools 18 Local Training Courses 24 Major Research Funding Available06 Latest Medical Productsresearchers feature Healthcare grapevine Leadership Feature 26 Aunty Research Agony07 Researchers in The Making08 Researchers & Their Finished Work 14Knowing our healthcare leaders10 Research Support & Allied Health PersonnelYour Newsletter, Your Comments mail us Editorial WorkgroupDo you have... Research articles to share? Research topics that you want covered? Comments /Feedbacks on published Catalyst Newslettercontents of this newsletter? Comic strips / Cartoon Illustrations that is science / research-related that can bring smiles to c/o Research & Development Officeyour colleagues? National Healthcare Group Pte LtdIf you have answered “YES”to any of the above, we invite you to write in and share with us your throughts, feedback on 6 Commonwealth Lanepublished articles or cartoon clips (original materials, jpeg format please). And if your contribution is accepted for print, we #04-03 GMTI Buildingwill send you a token of appreciation with compliments from the Editorial Workgroup! Singapore 149547Do remember to add in your contact details, where applicable for our future communications with you. email [email protected]

LATEST RESEARCH NEWS research news 3Inviragen Aims to Continue Development of INV21An Inactivated Vaccine Candidate for the Prevention of Hand, Foot and Mouth Disease caused by Enterovirus 71Dr Joseph SantangeloChief Operating OfficerInviragen, Inc.Hand, Foot and Mouth Disease (HFMD) is 35/36 subjects completed the study through to address the ongoing regional HFMDcaused by enteroviral pathogens such as Day 56. Most common adverse events in epidemic, and ultimately reduce mortality andenterovirus 71 (EV71). Although this is INV21 and placebo subjects (cough: 5/36 morbidity due to EV71 infection. INV21 wasgenerally a self-limiting disease characterised subjects; rhinorrhea: 5/36 subjects; pyrexia: developed in Singapore by local researchersby fever, mouth ulcers, and a rash, HFMD 4/36 subjects; influenza: 3/36 subjects) were and Inviragen desires to continue this clinicalcaused by EV71 can lead to viral meningo- mild and time-resolved. Minimal reactions program in Singapore.encephalitis, myocarditis or poliomyelitis-like were observed at the injection site, withparalysis, and may be fatal. similar profiles seen at both dose levels. It is hoped that INV21 will be a successful product to meet anEV71 and HFMD are endemic in Asia, Mild (Grade 1) pain, tenderness and pruritis unmet clinical need not only incausing significant morbidity, mortality and were reported in 1 subject in each treatment Singapore, but also more widelyeconomic impact in recent years. INV21 is a group. Grade 1 erythema and induration were in Asia. Development of vaccinepurified, inactivated EV71, alum-formulated reported in 1 subject in High Dose group. No candidates like INV21 is part ofvaccine, developed for the prevention of clinically significant changes in chemistry, the industry’s efforts to addressHFMD caused by EV71. Inviragen recently haematology and urinalysis parameters were this growing problem of HFMDcompleted a Phase 1 clinical trial of INV21 observed in either group. infections in Asia. Inviragen isin Singapore with Dr Paul Tambyah of the focused on developing vaccinesNational University Hospital as the Principal Highest EV71-neutralising antibody titres to protect against infectiousInvestigator. were detected 2 weeks post second dose diseases worldwide. (Day 42), with all subjects seroconverting (≥Thirty-six healthy males and females aged 21 4-fold rise in titre compared to baseline) at Founded in 2005 with offices in Singapore,to 45 years were enrolled into a randomised, this time point (Low Dose GMT = 323; High Colorado and Wisconsin, Inviragen’s investorsdouble-blind, placebo-controlled study at Dose GMT = 452). Long term assessments include EDBI subsidiary Bio*One Capitalthe Investigational Medicine Unit, National through Day 196 are now complete and the Pte. Ltd. (Singapore), Phillip Private EquityUniversity Hospital, Singapore. Subjects immune responses continue to be positive. (Singapore), Charter Life Sciences (Palo Alto,were enrolled to either Low Dose [12 on CA) and Venture Investors (Madison, WI).INV21 (0.6 mg EV71/dose); 6 on placebo] This “first-in-man” trial demonstrated thator High Dose [12 on INV21 (3 mg EV71/ INV21 is a safe and immunogenic vaccine See www.inviragen.com for more details.dose); 6 on placebo] group. Subjects candidate for the prevention of HFMD causedreceived two injections (Day 0, Day 28) by EV71. An appropriate team of clinicalintramuscularly, and were followed for safety investigators is now being organised toand immunogenicity assessments through conduct a Phase 2 clinical trial in Singapore.Day 56. The planned Phase 2 clinical trials are neededPhoto courtesy of Oxford University Clinical Research Unit, Vietnam and used with permission. ISSUE 12 JUL / AUG 2012

4 research news RESEARCH IN THE COMMUNITY Implementation Research Why it is useful, and why it is an exciting new frontier for researchersDr John OvretveitDirector of Research, Professor of Health Innovation Implementation and EvaluationMedical Management Centre, The Karolinska Institutet, StockholmEmail: [email protected] took me an embarrassing length of time research area with the significant potential Implementation researchas a researcher to realise that obtaining to help make improvements more effective. is not just about studyingevidence that a change is effective, is only a Already the value of some of such research how one health serviceminor ingredient in achieving improvements can be seen in the journal “Implementation takes a proven treatmentin healthcare. Much more important are Science”, for example. and spreads it to differentthe actions taken to enable clinicians and units within the service.managers to make the changes. Some of Many clinicians and researchers know aboutthese actions are local, like those taken by an the changes which will reduce central-line It is also about finding out which changes needimplementation project team. Some actions blood stream infections – the CLABSI bundle. to be adapted to fit the service, and which partare by people at higher management levels of of the change can and cannot be adapted forthe health system and which create conditions In Michigan State, 102 Intensive Care the change to be effective. This involves usingand incentives to encourage the change, as Units (ICUs) took part in a breakthrough new types of research methods such as actionwell as reducing factors which hinder the collaboration to reduce CLABSIs to zero. evaluation methods. If I had to make my careerchange. choice again, I would have stated this field Implementation research was able to find out of research as the combination of practicalImplementation is how people put knowledge why some of the ICUs which implemented relevance and scientific challenge is oneinto practice to improve health or healthcare. these changes, were much more successful which attracts me. At this time of constraintsResearch into implementation seeks to than others. on finance and personnel and the imperativeunderstand what people do that is effective for change in healthcare, implementationfor changing clinicians’ behaviour or In the successful ICUs, the changes were research promises to be of great value and ahealth service organisations so as to adopt sustainable due to professional and effective fertile ground for scientific research.changes which has been proven elsewhere. project team management, on top of a cultureImplementation research is a new and rapidly and higher level leadership that was absent indeveloping field, and is an exciting new the lower performance ICUs.FREE SUBSCRIPTION YES! I would like to recommend my colleagues/ friends to receive a free copy of Catalyst. Please fill out their name, job title and email address. Mr Ms Dr Name: Which of the following best describes your organization business? Designation: Company: Biotechnology Legal Services/Patent Services Office Address: Pharma Distributor/Dealer/Supplier Medical Technology Research/Training/Education Institution Office Telephone/Fax: Bioinformatics GovernmentCATALYST ACCELERATING RESEARCH Biologicals Healthcare Others (Pls Specify) Catalyst: A newsletter for the Research Community in Singapore (Quarterly) Drop us a mail at [email protected] or fax back to us at 6496 6111.

RESEARCH SERVICES research news 5IMH DevelopsPositive MentalHealth InstrumentMs Deborah KohInstitute of Mental HealthInstitute of Mental Health (IMH) The other lead researcher was Ms Janhavi 4 Interpersonal skills – this dimensionhas developed and validated Vaingankar. An additional implication of strongly contributes to all other aspectsan instrument to measure using this instrument in a research setting of mental health and the skills are crucialthe positive mental health of will be to measure and observe changes to in helping one develop and maintain goodSingapore residents. The Positive positive mental health among the Singapore relationships, which in turn will provide theMental Health (PMH) instrument population over time. support and network needed during times ofis one of the first validated scales distress.on mental health developed in * Some 2,500 Singapore residentsAsia that is culturally and locally participated in the development and 5 Personal growth & autonomy –relevant to our population. validation of the PMH instrument which was knowing one’s goals in life and ways to conducted from April 2008 till February 2011. achieve them is a sign of good mental health.Traditionally, instruments to measure mental Focus groups and surveys were conducted It reflects on a person’s level of confidence,health and well-being are largely developed among Chinese, Malay and Indian adult freedom, sense of purpose, and the ability toand often used within Western populations; residents, aged 21 to 65 years old. self-evaluate and take control of situations.this compromises their validity in othercultures. The multi-dimensional instrument KEY ASPECTS OF THE POSITIVE 6 Global affect – the experience ofcovers all key and culturally appropriate MENTAL HEALTH INSTRUMENT positive mood is a sign of mental health.domains of mental health, and can be used Being calm, happy and enthusiastic areto compare levels of mental health across The PMH instrument includes six dimensions indicative of emotional stability and vitality.different age, gender and ethnic groups. (47 items or statements) and encompasses This is a more transient dimension, yet the the notion that mental health can be achieved most predictive of one’s recent experiences.The PMH instrument was developed by IMH’s by the balance, influence and strengthsResearch Division in partnership with the of multiple domains. The six dimensions Although the key domains of positive mentalMinistry of Health, Nanyang Technological identified for positive mental health are: health are similar to the other reports fromUniversity , National University of Singapore Western countries, the study highlightedand RAND Health, a research division within 1 General coping – how a person reacts that spirituality was deemed important in theRAND Corporation, an American non-profit and copes during stressful situations context of Singapore.research organisation. The PMH instrument and his ability to think positively and engagewas developed as part of the Singapore in choice activities. This article was first published in IMH LINKMental Health Study. (MICA (P) 162/07/2011), a quarterly 2 Emotional support – the assurance publication by Institute of Mental Health,“The PMH instrument can be used to collect of feeling loved and wanted by a January ~ March 2012 Issue.data on individuals and various subgroups person’s family and friends is important toin the population which would be crucial help him cope with difficult life situations. It The Instrument is protected by worldwidewhen reviewing existing mental health policy provides compassionate, realistic counseling copyright laws and treaty provisions. If youand services. Such information may also and care which helps the person to share his wish to use or enquire about the instrument,contribute to adequate mental health training, burdens and fears with others. please contact the following:education and public awareness, and lead toimproved health outcomes in the population,” 3 Spirituality – this domain covers both Assistant Professor Mythily Subramaniamsaid Dr Mythily Subramaniam, Deputy spiritual and religious practices Deputy Director, ResearchDirector of Research, and one of the two IMH and beliefs that influence one’s faith and Institute of Mental Health, Singaporeresearchers who led the study. behaviour in life. It contributes to positive mental health as a coping mechanism and Tel: +65 6389 3633 helps in building strong social support and Fax: +65 6343 7962 networks. Email: [email protected]

6 research news RESEARCH TOOLS H5N1 Test Trial for Healthcare and Wellness Kiosk at Woodlands Polyclinic National Healthcare Group Polyclinics (NHGP) has partnered A*STAR (Agency for Science, Technology and Research) to develop Healthcare and Wellness Kiosks that allow patients to measure and record their health conditions prior to consultation. The project’s test trial was launched in Woodlands Polyclinic on 10 May. Fully funded by A*STAR, the Healthcare and Wellness Kiosks allow patients to enter their medical conditions and symptoms relating to Upper Respiratory Tract Infection (URTI) while getting their weight measured. This information will then be transmitted to their personal medical records which will be viewed by the doctor during consultation. The Kiosks cut down process waste as they eliminate repeated information gathering at different service stations as all presenting symptoms are captured by the Kiosk during registration. After the completion of the test trial, the clinic team will launch phase two of development which allows the Kiosks to measure patients’ temperatures as well as assign those who display symptoms of flu and fever to the URTI cluster. Article courtesy of NHGP Corporate Communications LATEST MEDICAL PRODUCTSLaunch ofConviDose™:Safer, EasierMedicineOn 8th May, the National HealthcareGroup Pharmacy (NHGPh) launchedConviDose™ - Singapore’s First Multi-doseMedication Management Services at theInstitute of Mental Health. The guest-of-honour Professor Chee Yam Cheng,CEO, NHG delivered the opening addressand together with Ms Chan Soo Chung,Executive Director of NHGPh officiated theConvidose™ launch. Representatives from nursing homes, (Top)1. Professor Chee Yam Cheng, CEO, National Healthcare Group and Ms Chan Soo Chung, Executive Director partners of NHGPh, media, senior NHG Pharmacy with the nursing homes representatives. (Left to Right) 2. Professor Chee Yam Cheng, CEO, NHG management staff from NHG and IMH together with Ms Chan Soo Chung, Executive Director, NHGPh officiate the Convidose™ launch. 3. Pharmacy attended the event. They were given a technician collecting the Convidose™ sachet from the Automated Tablet Dispensing and Packaging System (ATDPS) 4. tour of the Pharmacy Services Centre- Pharmacy Services Centre, NHGPh’s centralized facility for Convidose™. NHG Pharmacy’s centralized facility for ConviDose™ – at IMH. With Convidose™, patient’s medicine dosage can be conveniently pre packed into individual sachets, according to the stipulated quantity and time the pills need to be consumed. Article courtesy of National Healthcare Group Corporate CommunicationsCATALYST ACCELERATING RESEARCH

RESEARCHERS IN THE MAKING researchers feature 7Development of sustained releaseganciclovir implant for treatment of CMVretinitis in HIV-AIDS patients.CLINICAL LEAD-PRINCIPAL INVESTIGATORDr Rupesh Agrawal, Associate ConsultantDept. of OphthamologyTan Tock Seng HospitalTECHNICAL LEAD-PRINCIPAL INVESTIGATORDr Terry W J Steele, Assistant ProfessorMaterials Science & EngineeringNanyang Technological UniversityProject was awarded the NTU-NHGInnovation Seed Grant (ISG) of SGD 48,000Cytomegalovirus in AIDS Current local treatment involves injecting vitreous over several months while maintainingpatients: The Human antiviral drugs directly into the vitreous, a an adequate concentration of drug in theImmunodeficiency Virus (HIV)/ therapy that requires multiple injections, week vitreous cavity.Acquired Immune Deficiency after week. Repeated ocular injections can beSyndrome (AIDS) pandemic, traumatic, with risk of ocular complications like The biodegradable implant is designed tonow affects between 30.6 and endophthalmitis, retinal detachment and drug suppress viral replication, halt the progression36.1 million people world-wide. resistance. of disease, minimize retinal damage, prevent drug resistance, prevent local complicationsThe human immunodeficiency virus (HIV) Importantly a patient with CMV retinits needs to and preserve visual function. Secondaryhas pervasive effects on culture, economics, come over to eye clinic for repeated injections operations for removal will not be necessary,policy and human development. All organs and there is always a chance of patient as the polymer components are designed tocan be affected by complications of HIV/AIDS, getting defaulted for repeated injections. slowly dissolve and be metabolized into theincluding the eye. Many HIV+ patients develop Hence, development of cost effective long tissue.eye complications, both infective and non- lasting sustained release ganciclovir implantsinfective, CMV (cytomegalovirus) retinitis being are currently needed for safe and effective Collaborations between clinicians and implantthe most common. Specific ocular therapy is treatment of cytomegalovirus retinitis. engineers: This project allows a synergy of longcritical to avoid blindness in the early months term collaboration between technology andbefore immune recovery can occur, or if Peri-ocular implants designed for patient medicine. In the long run, the technologistsantiretroviral therapy is unavailable. comfort and long-term drug release: To and clinicians will work towards facilitating the circumvent the practical hurdles in delivering similar platform for many other therapeuticsGanciclovir has traditionally been considered anti-CMV drugs to the retina, collaboration required to be used for posterior segmentthe recommended treatment for CMV retinitis; between TTSH and NTU was embarked on disorders such as corticosteroids for chronichowever due to side effects and the possibility designing a unidirectional nano-drug delivery uveitis and anti-vascular endothelial growthof developing viral resistance, local therapy is pellet that provides drug delivery into the factors for age related macular degeneration.preferred.Current treatment for CMV retinitis: Ganciclovirhas traditionally been considered therecommended treatment for CMV retinitis.Systemic therapy with intravenous ganciclovirwas initially the only option available butsubsequently, other antiviral drugs were alsoused in treatment of CMV retinitis including theuse of cidofovir, prodrug of gancicloviri.e., vala-ganciclovir, and intravenous foscarnet.Unfortunately, these drugs are limited by itscost constraints and systemic side effects. Localtherapy, in the form of intra-vitreal injectionswith ganciclovir and cidofovir was pursuedsince ocular infection was the most common NTU-NHG Innovation Seed Grant 2011t Award presentation to Dr Rupesh Agrawal (right) by Prof Stephen Smith,manifestation of CMV. Vice-President Research, NTU and Founding Dean of Lee Kong Chian School of Medicine (left) ISSUE 12 JUL / AUG 2012

8 researchers feature RESEARCHERS & THEIR FINISHED WORKThe Impact of Genetic Variationin the HIV-1 Protein Coat onImmune Cell DeathDr Ng Oon TekConsultant, Department of Infectious DiseasesTan Tock Seng HospitalDr Ng completed Internal Medicine training in Singhealth cluster and obtained the MRCP(UK) and MMed (Int Med) in 2004.Subsequent Infectious Disease subspecialty training was completed in Tan Tock Seng Hospital (TTSH) in 2008. He received aMaster of Public Health degree from Johns Hopkins School of Public Health in 2010 sponsored by a National Medical ResearchCouncil Overseas Research Fellowship. As a recipient of the NMRC Overseas Research Fellowship, Dr Ng completed the MPHdegree followed by a year-long research attachment with a US NIH funded group. Dr Ng has an interest in research integratingpublic health, laboratory medicine and clinical medicine to improve patient outcomes. Accordingly, he works closely with clinicalcolleagues, and the Ministry of Health Communicable Disease Division, as well as running funded studies in the TTSH InfectiousDisease Research Laboratory. He is the TTSH site investigator for the Treat Asia HIV Observational Database, a US NIH fundedproject examining HIV in Asia.Human Immunodeficiency Virus (HIV) is Recently, funded by a National Medical approach to answering the question.extremely variable genetically. Just as no Research Council training grant, a The research is potentially important attwo human beings are similar, potentially no collaborative effort between investigators at both international and local levels. At antwo HIV viral particles are exactly the same. the Communicable Disease Centre and Johns international level, most of the immenseA major reason for this variability is the Hopkins Medical Institution, documented body of HIV research is conducted on theinconsistent error checking of the enzymes the emergence of a new strain (or hybrid) Western subtype B strain, and differences inwhich copy the HIV genetic material. of HIV in Singapore, formed as a result of biology and clinical behavior of non-B strains intermixing of genetic materials from the could render those results not immediatelyThis is multiplied by the production of an previously documented dominant strains. This transferable to other regions.average of 1,000 million viral particles a day phenomenon had been documented globallyin an infected person. Researchers using 50 times prior to our report, and is a marker For example, a recent publication fromlaboratory techniques have been able to of active disease transmission. our group highlighted the finding thatdefine subtypes, or strains, of HIV, in different Singaporeans infected with the CRF01_AEgeographical regions in the worldwide The current Transition Award grant funded strain present with more severe immune-pandemic, now infecting more than 30 million project examines whether different strains compromise and do not respond aspeople. of HIV affect the immune system of infected well to treatment, as subtype B infected individuals differently. A prior published counterparts. At a local level, the impact ofA unique feature of the HIV epidemic in study conducted by the same group above HIV strain on patient outcome is important asSingapore is the presence of two different had documented that CRF01_AE infected public health and treatment strategies maystrains, scientifically labeled “subtype B” and individuals lost immune cells at a much faster need to be adapted for the differences.“CRF01_AE”, documented in the mid-1990s. rate than subtype B infected individuals.This two strains are likely (although unable to I thank God for very supportive mentors, bothbe proven beyond doubt) to have arisen from In this current grant, we plan to conduct within TTSH, at other institutions in Singaporedifferent geographical areas. laboratory experiments in collaboration and at Johns Hopkins, who have provided with the University of Texas to determine if a lot of insights into medical research. TheThe “subtype B” strain accounts for difference in the HIV-1 protein coat, a major availability of funding from NHG-level andapproximately 90% of HIV infection in region of the virus which interacts with National Medical Research level grants haveWestern countries, and is believed to have immune cells, affects the rate of immune also been highly enabling in these endeavors.entered Singapore from there. The “CRF01_ cell death. We are also planning to monitor Thanks also to all the collaborators at NationalAE” strain is the overwhelming strain in patients infected with all the 3 major strains University Hospital, A*STAR (ETC and IBN),Southeast Asia, the likely source of entry to (subtype B, CRF01_AE and hybrid) to Johns Hopkins, and University of Texas, whomSingapore. observe for differences in clinical features. I have worked closely with over these few Hence, this study adopts a bench and bedside years.CATALYST ACCELERATING RESEARCH

RESEARCHERS & THEIR FINISHED WORK researchers feature 9The Road of DiscoveryReflections of a Young Clinician Investigator from IMH taking the path that is less travelledDr Jimmy LeeConsultant PsychiatristInstitute of Mental HealthDr Jimmy Lee is a National University of Singapore (NUS) trained medical doctor. He is currently Consultant Psychiatrist in theGeneral Psychiatry Department and Director of the Clinical Trial Unit at Institute of Mental Health (IMH). He spends more than halfhis time on research work and continues to see outpatients and heads the Annual Review Clinic team. He has also started to mentornew investigators through an intramural grant. Being awarded the Transition Award from National Medical Council (NMRC) is a strongtestament to his work and dedication to research and clinical work for the betterment of patients with mental illnesses. In this issue, theeditorial team finds out from Dr Jimmy Lee himself, about choosing the path that is less travelled by others.Psychiatry biomarker might be feasible, easily accessible School of “Hard Knocks”The practice of psychiatry today has come and provide additional clues to aid the Obtaining this Transition Award is aa long way with a deeper understanding of psychiatrist. culmination of years of preparations and hardthe science behind the art and with more work. It all started from a simple researchtreatment options available. However, This naturalistic study seeks to expand on the project that my mentor got me on 8 yearsthere are numerous enigmas that continue pilot, to recruit and follow up a larger group ago, which led me down the “slippery” pathto confound psychiatrists daily. Using of participants over a longer duration of time. towards more research hardship. The pilotschizophrenia as an example, questions At regular intervals, clinical status will be studies and follow on study mentioned abovesuch as what causes it, which medications monitored and blood samples will be collected, were instrumental in helping me obtain theare most suitable and who is at greatest risk processed and stored. Transition Award, and they would not haveof developing treatment resistance or side been possible without the small grants and theeffects to the treatments remain unanswered. Our group will attempt to validate the lipid- NHG Small-Innovative Grant (SIG). based peripheral blood signature in this group,Schizophrenia is a serious mental disorder and monitor its changes in relation to clinical A point I often make is the need forwith potentially disabling outcomes. One of response and treatment. What is also unique in continued education to understand researchthe main drawbacks in psychiatric practice this study is the parallel recruitment and follow methodologies. I have been trained for 5 yearstoday is the lack of an objective measurement up of a group of healthy controls, to examine to understand the language of medicine andsuch as a biomarker that clinicians can rely how these lipid markers vary over time and took on further education over the years inon. A central dogma in psychiatry has been the influence of dietary and lifestyle factors. the forms of the NHG Clinician Leadershipthat psychiatric disorders are primarily brain This information is important in understanding in Research Programme, and the Master ofdisorders, and most research has focused on normal variations so that our team is better Clinical Investigation (MCI) to understand thethe brain. There is now increasing evidence able to filter the noise from the true signal. language of research.that psychiatric disorders do not just affect thebrain, but also on peripheral tissues – at least While the study focuses on identifying Telling others that I am embarking onthe medications certainly do. biomarkers as the longer term aim, I research (including my family) never fails also believe in research that benefits the to elicit some form of peculiar response –Journey of Discovery participants. A feature of this study is that frequently I would get frowns, worried looks,Our initial studies have shown that it was participants will have their Body Mass Index and queries about my own sanity, to the verypossible to identify a lipid-based signature (BMI) calculated, blood pressure taken, occasional interested “tell me more” look.in red blood cell membranes, and a gene fasting lipid and glucose profile measured, Whenever I face challenges, an adage that aexpression signature in peripheral blood of and the results mailed to them. This pertinent wise psychiatrist once said comes to mind –patients with psychosis. A follow on pilot study information will hopefully provide the “The mind is the last frontier” – a statementdemonstrated the stability of the lipid-based participants a snapshot of their own metabolic applicable to my own pursuits, as well mysignature over a short period of time after health, and encourage them to either maintain patients’.anti-psychotic medication exposures. This their healthy lifestyle, or seek help if needed.lead us thinking that a peripheral blood-based ISSUE 12 JUL / AUG 2012

10 researchers feature Research Support & Allied Health PersonnelContinuous MNHs GDo-OreHeRnPLPimC, MIPraCnhdarCleCsRWPoancgc,rMedsiHteudLsitqaifnf (FArobmsenLte:fMt: sMJsoFbeylnicaiaHWo)ong,Educationand FurtherCertificationof OHRPP StaffThe NHG Office of Human Research program. The CIP program was developed professionals would be the Society of ClinicalProtection Program (OHRPP) in 1999 by Public Responsibility in Medicine Research Associates (SoCRA) certificationis committed to the continuing and Research (PRIM&R) and tests candidates’ program.professional development (CPD) knowledge in these four major areas:of staff to ensure that staff is This certification program validates andconfidently equipped with ethics 1. Foundations and concepts of IRB practice accredits Clinical Research Coordinators orknowledge to facilitate efficient 2. Organizational and personnel knowledge Professionals with at least 2 years of relevantand high quality ethics review and 3. IRB functions and operations experience, and who are able to demonstratemaintain high standards of human 4. Records and reports professional competency in the area ofresearch protection. clinical research. The CIP credential is a validation of anAn important CPD opportunity for individual’s professional experience and The NHG OHRPP is proud to announceInstitutional Review Board (IRB) staff to competency in IRB and HRPP administrative 100% passes among staff who undertookadvance and demonstrate their competency practices and strengthens the administration of the above programs in March 2012.would be the Certified IRB Professional (CIP) IRB processes. Congratulations to all Certified Clinical Research Professionals (CCRP) and Certified Another platform to accredit clinical research IRB Professionals (CIP)!CATALYST ACCELERATING RESEARCH

Q+ ualitéNHG RESEARCH QUALITY MANAGEMENT PROGRAM 11 money 1111The program with a mission to ensure and enforce the responsibleconduct of research meeting high ethical standards.Informed Consent DocumentationThe Use of Short Form Consent FormsWhat is the Short Form Consent? investigator, translator, impartial witness and Patient Information Sheet & Consent Form). subject. The subject would then sign on theInformed consent must be obtained from all Short Form Consent Template which was in the For Investigator Initiated Studieshuman subjects, prior to their participation in language understandable to him/her. For all types of research studies (for theany research studies approved by the NHG recruitment of non-English speaking subjects,Domain Specific Review Board (DSRB), unless Health Sciences Authority’s where a fully translated ICF is not available),the process has been waived by DSRB. Recommendation on the use of Short Form investigators are allowed to conduct the Consent informed consent process for the non-EnglishIn addition, DSRB recognizes the requirements speaking subjects using the DSRB-approvedof Good Clinical Practice and United In HSA’s recommendations of the informed Short Form Consent Template. However, theStates Food & Drug Administration Code consent process, for subjects who were unable short consent form must be used together as aof Federal Regulations, that the informed to read the informed consent form, there is no complete set with the DSRB-approved Englishconsent document should be in a language legal provision for the subjects to sign on the version Patient Information Sheet & Consentunderstandable to the subject. However, in Short Form Consent alone (without signing on Form.view of the budget constraints of investigator- the original English consent document).initiated research studies, DSRB recognizes • The Subject, Investigator and Impartialthe fact that sometimes it is not possible for Hence, in order to harmonize with HSA’s witness need to sign on BOTH the Shortinvestigators to develop translated versions of requirements, DSRB will be recommending Form Consent Form and the English versionthe consent document. some changes to the practices of informed Patient Information Sheet & Consent Form. consent for non-English speaking subjects.Considering the above, DSRB created a Short • These 2 documents are considered a setForm Consent Template for these researchers New Recommendations on the Use of Short of documents, and a copy of the full set ofto obtain consent from non-English speaking Form Consent documents is to be provided to the subject.subjects, where a translated version of thecomplete set of consent documents is not Consent from non-English speaking subject • A document footer and a page numberavailable. The Short Form Consent Template The preferred method of obtaining informed will be required as essential elements onis intended to be used as a tool, in addition to consent from non-English speaking subjects, these documents. This is an added measurethe original English consent document, and is to provide the subjects with consent forms to ensure the study team and the subjectthe consent process and procedure has to be written in the language understandable to the understand that they are indeed a set ofperformed or obtained in the presence of an subject (i.e. translated version of the complete documents. IISSSSUUEE 1122 JJUULL // AAUUGG 22001122

1122 money • A certified translation is preferred. This released to the research community in should be accompanied by a letter the coming months as DSRB seek to help (continued from previous page) of certification from the translator or Investigators ensure compliance to the translation service provider. recommended revisions in the informed Translation of consent documents consent processes. For investigator-initiated research studies, • For Investigator-Initiated studies, whereby investigators should include the costs of cost of translation is a factor of concern, Other References: consent documents translations into grants and DSRB accepts documents translated by Health Sciences Authority Website (Frequently contracts. It is the responsibility of the Principal an individual fluent in the given language Asked Questions) - [H] INFORMED CONSENT Investigator to ensure that there is provision of in place of a certified translation. A letter FORM (ICF) adequate resources to obtain proper informed from the translator describing their http://www.hsa.gov.sg/publish/hsaportal/en/ consent from the subjects. qualifications should be provided with the health_products_regulation/clinical_trials/ translated documents. faqs.html#(H) DSRB has developed the following More information on the guidance will be recommendations for translated consent documents, applicable for all types of research studies:Protocol Non-Compliance:Compromising the Privacy andConfidentiality of Subject’s InformationBackground subject identities in a separate and secured [PCR 501-B05 Item 9.] To protect theA multicenter study involving several sites document to minimize the risk of exposing confidentiality of subjects, the CRF should notin Singapore recently have been sending subjects’ identities. have a provision to enter the subjects’ name.hardcopies of the Case Report Forms (CRFs) The CRF should be linked to the subject onlyfrom the various participating sites to the c. Research data sent outside the institution by subject identification code and if needed theoverall Principal Investigator for consolidation should not contain any subject identifiers, subject initials. Sticky labels with the subjectand filing. However, attached to the CRFs unless specific approval has been obtained name and other personal information thatwere also copies of the source documents and from DSRB. Principal Investigators should is generally used in institutions for medicalrecords from the various participating sites. also check their institution policies with records and other forms should never be stuckThis included subjects’ admission records, regards to data management or transfer of on CRF pages. When laboratory test resultsmedical history, etc. data outside of the institution and obtain are filed as part of the CRF, the subjects’ name necessary approval before releasing should be obscured.Findings & Implications patients’ records to members locatedThe study team had attached a copy of source outside the institution. PCR 501-B05 (Definition) b. Source Data – Alldocument/records with the CRFs to facilitate information in original records and certifiedin the verification and clarification of potential d. If there is a need to send copies of copies of original records of clinical findings,discrepancies. source records outside your institutions; observations, or other activities in a clinical subjects’ identifiers should be obliterated trial that is necessary for reconstruction andHowever whilst doing so, the study team had or obscured.. This can be done by using evaluation of the research. Source data areinadvertently compromised on the research a black marker and photocopying the contained in source documents.subjects’ privacy and confidentiality as records document to ensure that the subjectcontaining their identifiers and medical identifiable information cannot be seen. The NHG Proper Conduct of Researchinformation had been sent out to the various Standard Operating Procedures are foundinstitutions. References from NHG – Proper Conduct of at the following portal: Research SOPs (PCR-SOPs):Tips and Recommendations http://www.research.nhg.com.sg/wps/ [PCR 501-B08 Item 4.] The CRFs should not wcm/connect/romp/nhgromp/resources/a. Data entry should be completed at site and contain patient identifiers such as name, date research+sops data should be verified with source data/ of birth, address, etc. Each subject should be documents before it is entered into case assigned a unique subject identification code report forms. which should be used in the CRFs, serious adverse event reports, UPIRTSOs and anyb. Case report forms should not contain any other research related data. In addition to the subject identifiers (eg. Name and NRIC subject identification code, subject initials may number). Instead, unique codes could be also be entered. The link between the subject assigned to subjects when data is being identification code and the subject identifiers collected. These codes would be linked to should be stored in a separate document.CCAATTAALLYYSSTT AACCCCEELLEERRAATTIINNGG RREESSEEAARRCCHH

money 1133Protocol Non-Compliance:Compromising the Privacy andConfidentiality of Subject’s InformationQ1: What is the Purpose of having Source laboratory notes, memoranda, subjects’ diaries collected (the greater the sensitivity, the Documents? or evaluation checklists, pharmacy dispensing greater the need for privacy) records, recorded data from automated The fundamental purpose of source instruments, copies or transcriptions certified d) Method of Data Collection (e.g focus group, documents is to confirm the existence after verification as being accurate copies, individual interview, covert observations) of the subject; confirm the validity of the microfiches, photographic negatives, microfilm trial conducted and the integrity of data or magnetic media, x-rays, subjects files, and Maintaining Confidentiality: collected. Therefore, in a clinical trial, records kept at a pharmacy) at the laboratories, Confidentiality pertains to data and is explained records on which clinical observation are and at medico-technical departments involved as treatment of information that an individual initially recorded are considered source in the research. has disclosed in a relationship of trust and documents. These records are also Case report forms are printed, optical or with the expectation that it will not be divulged legitimate raw data that supports a trial’s electronic document designed to record all to others without permission in ways that are findings. At an investigational site, usually of the protocol required information for each inconsistent with the understanding of the a hospital, the medical record is often the study subject. original disclosure. source documentation. It can also be a computer print out of laboratory value References: For the maintenance of confidentiality, the results or patients’ diaries. following factors are to be considered: • Singapore Guideline for Good ClinicalQ2: What are source documentations and Practice (SGGCP a) Research Design (minimizing the need to how is it used in clinical trials? collect and maintain identifiable subject • NHG PCR SOP 501-B05: Documentation information) Source documentation serves to substantiate the integrity of the trial data • Good Clinical Practice: A Question & b) Collecting and maintaining Identifiable Data collected, which include original documents Answer Reference Guide, May 2011 (protocol includes safeguard to maintain related to the trial, to medical treatment, (Published by Barnett Education Services) confidentiality of data and data security and history of the subject. To substantiate appropriate to the degree of risk from the integrity of the trial data collected, the Reference Guide: Protecting Privacy and disclosure) information on a subject’s medical record Maintaining Confidentiality should correspond to the data on the case c) Provisions to maintain confidentiality of report form, and in turn should support the The Office of the Human Research Protection data (should be included in the protocol) data listings and statistical results which are Programme of UCLA published a quick provided to regulatory agencies. reference guide or tool intended to aid d) Limit access to Data (the informed consent researchers and IRB members to ensure that states who should have access to the data, According to Singapore Guideline for adequate provisions exist for the protection of usually authorized personal e.g auditors, Good Clinical Practice (SGGCP) 4.9.3, data research participant privacy, the maintenance regulatory inspectors) reported on the CRF, that are derived from of confidentiality of identifiable research data source documents, should be consistent and data security. For more detailed information, reference to with the source documents or the the guidance document is recommended (link discrepancies should be explained. Some of the issues to consider in protection of below). subject’s privacy are explained in this guide.Definition/Glossary: Reference:Source data are information in original records Protecting Privacy: UCLA Office Of Human Subject Protectionand certified copies of original records Privacy is about people and their control over Program (OHRPP)’s Quick Reference:inclusive of original records of clinical findings, the factors of extent, timing, and circumstances Protecting Privacy and Maintainingobservations, or other activities in a clinical of sharing oneself whether physically, Confidentiality in Research, AAHRPP Elementstrial that is necessary for reconstruction and behaviorally, or intellectually with others. – II.2.B., II.3.D-F, II.5.A.evaluation of the research. Source data arecontained in source documents. For privacy in research, the following factors are considered:Source documents refers to all documentsthat have source data, including original a) Subject Population (cultural norms and agedocuments, data, and records (i.e. hospital may affect privacy preferences)medical records, clinical and office charts, b) Recruitment Methods (acceptable methods of identifying and contacting subjects) c) Sensitivity of the Information being IISSSSUUEE 1122 JJUULL // AAUUGG 22001122

14 healthcare leadership feature Knowing our Healthcare Leaders Associate Professor Leo Yee Sin, Head, Department of Infectious Disease, Tan Tock Seng HospitalAssociate Professor Leo Yee Sin (third from left) with collaborators of STOP Dengue 1. What are your thoughts on the works well and collaborates well with We also collaborate with other healthcare current state of collaborative many other specialties. institutes in Singapore, with the first inter- research in your institution? hospital infectious disease network set Examples of intra-hospital collaborations up for a clinical trial in dengue, and with a Tan Tock Seng Hospital (TTSH) prides currently in progress include antibiotic polyclinic network for recruitment of early itself as a service-oriented hospital. It utilization with intensive care physicians dengue infection. was founded as a pauper’s hospital and and pharmacists, bone and joint infectious is the second largest acute care general with orthopedics and viral encephalitides Industrial collaboration has been initiated, hospital. TTSH houses many renowned with neurologists at the National for example in dengue diagnostics, and clinical groups and through the years has Neuroscience Institute. we have started exploring international invested in clinical research aiming to collaborations with other centers improve patient care. The award of the flagship infectious experienced in dengue research. disease translational clinical research Continued collaborative research will TTSH has a particular strength grant to STOP Dengue led by CDC depend on further grant support, and we in infectious disease housing the in 2008 promoted inter-institution have joint proposals for diagnostics with Communicable Disease Centre (CDC) collaboration, with active partners in NTU and A*STAR under review. which is also the National Outbreak National University of Singapore, Genome Response Centre that handled the SARS Institute of Singapore, Duke-NUS, 2. Is there a simple analogy that you and 2009 H1N1 influenza outbreaks. Environment Health Institute and other would use to describe the “As Is” Infectious disease is a unique non-organ local research institutes. and “To Be” state of your research specific sub-specialty that by nature in your institution?CATALYST ACCELERATING RESEARCH

Clinical research strengths at TTSH are into all areas of our research healthcare leadership feature 15 currently in health services outcome We contribute to ongoing national research given the high patient load and surveillance through our collaborators utilization, we hope to contribute to a more emphasis on service provision. While at the Environment Health Institute effective national healthcare system, the maintaining this emphasis which has (EHI). Our samples allow for molecular importance of which can be seen from the proven fruitful especially in infectious epidemiology studies to be done, which recent healthcare budget. We are currently disease and rehabilitation medicine, can detect strain shifts. The introduction engaged in international collaborations to we would like to move forward by of new strains of dengue viruses is investigate the applicability of our findings. leveraging on local expertise for example associated with fresh outbreaks as in implementation research. With the occurred nationally in 2007, and on a 5. On a lighter note, what do you like opening of the Lee Kong Chian School smaller scale with clusters of dengue most about your job? of Medicine based at TTSH with NTU serotype 3 reported in the news last and Imperial College, London, in 2013, year. Quick response is vital to detect Infectious disease, and in particular we hope to build our relationship with and stamp out these clusters and it was outbreak research is forever challenging: these universities and synergise with successfully managed. facing rapidly developing outbreaks from the strengths of NTU particularly in the Nipah virus to SARS to the 2009 H1N1 bioengineering. Collection of clinical virus isolates was pandemic, managing clinical operations critical to the development of a new while simultaneously ensuring high-quality3. What do you think are the qualities and improved mouse model of dengue research is being done keeps me on my of your institution that allows it to virus by A/Prof Sylvie Alonso at the toes. The potential to have a revolutionary catalyse collaborative research? National University of Singapore. This impact is a great source of satisfaction, for mouse model is now being used by other example with the global pandemics of HIV, As the second largest acute general researchers in our team to develop new influenza and dengue. Finally, bringing hospital in Singapore, with the pioneer ways to prevent and treat dengue. research findings back into the clinic to geriatric medicine department and improve patient care, safety, and cost continue strength in the care of older Development of the first serotype-- management is what I find most rewarding. persons, we are well placed to support specific, non-crossreactive human large clinical cohorts necessary for health monoclonal antibody against dengue 6. How do you handle the tight services operations research and clinical serotype 1 by A/Prof Paul MacAry at NUS demands of your schedule and yet translational research. The Communicable is another example of how clinicians were find time for your family? Disease Centre is also a key resource able to collaborate with immunologists in as its position as the national outbreak time-sensitive research. Our collaborators Strong family support has been absolutely response centre puts it in the best position responded to the availability of clinical critical to help me balance work and home to study a range of outbreaks. During the samples by also studying the T-cell life. Help from parents in childcare and 2009 H1N1 pandemic, clinicians moved response to dengue with major advances an understanding husband have brought fast to gather data while managing the in our understanding of lymphocyte our family through the difficult school-age emergent clinical situation. The plethora response to dengue. Plans are in progress years. Now my older girl has graduated of high-quality outbreak research that for clinical trials for the monoclonal from university and my second child is has been published is testament to antibody and other dengue treatments. awaiting national service. I can’t stress the willingness to collaborate not only enough how rewarding it is to be able to between clinicians in different disciplines, We have initiated a biomarker discovery balance work and family, especially as you but also with laboratory researchers. project with a range of collaborators with see your children grow up. expertise in genomics and transcriptomics4. Could you share an example of a (GIS), metabolomics (SMART), and 7. What do you like to do in your spare piece of collaborative research that lipidomics and proteomics (NUS) to time? Do you have any hobbies? you are involved in and how it has discover prognostic markers for severe benefited the various stakeholders? dengue. Together with collaborators from Reading good books and tending to my the Department of Statistics, NUS, we garden are two activities I would like to be As the Lead Principal Investigator on plan to pool data together to demonstrate, able to spend more time on. Unfortunately, STOP Dengue, the national flagship often for the first time, the utility of these the truth is there is very little spare time! infectious disease translational clinical new technologies for infectious disease, to research program, it has been my improve the management of dengue, and 8. Does your personality and love privilege to coordinate a spectrum of to spur new implementation technologies for your hobbies help in making research on this pressing disease with half with bioengineers and biotech companies decisions in your research work? the world’s population at risk. We see the to bring solutions to the clinic. backbone of the program as the two large What motivates me is finding answers to prospective cohorts, the primary-care Finally, in terms of healthcare outcomes, the real-life problems I face as a clinician. based EDEN (Early Dengue Infection and our clinicians at Tan Tock Seng developed, Being able to implement well-researched Outcome Study) and the hospital-based validated and modeled the cost-benefit and effective solutions is very rewarding. PADS (Prospective Adult Dengue Study) of a prognostic algorithm that prioritized This is what drives me through the process with a combined enrolment of over 3500 hospitalizations for dengue together with of deciding what issues will benefit from to date. These are critical sources of statisticians and economists at NHG and research, what research is currently clinical data as well as samples that feed NUS. By improving healthcare resource feasible and then using the findings in innovative ways to help patients. ISSUE 12 JUL / AUG 2012

16 collaborations in research COLLABORATIONS IN RESEARCH INFECTIOUS DISEASES Infectious diseases remain the leading cause An effort to make Singapore the preferred NUH, SGH and CGH documenting the of death worldwide. The threat of infectious location for innovative drug studies, research molecular epidemiology of HIV-1 in disease is imminent even in Singapore, despite on biomarkers and disease mechanisms Singapore. Regionally, CDC is the Singapore its excellent healthcare infrastructure and high for dengue, STOP Dengue aims to improve representative on the sole pan-Asian HIV standards of living. Singapore being a major collaborations between scientists and database - the Treat Asia HIV Observational global trading hub will continue to be plaqued clinicians, with the purpose of translating Database (TAHOD). The associated Treat by emerging infectious diseases like SARS, discoveries in the laboratory into interventions Asia Quality Assurance Scheme (TAQAS) HIV, H1N1, re-emerging infectious diseases that can improve dengue care. has also facilitated quality control for a locally like dengue and tuberculosis as well as drug developed genotypic resistance test at the resistant infections because of various factors The first three years of STOP-dengue’s CDC. like changes in the population demographics collaborative research has accomplished key and behavior and increased international research outcomes. The team of basic science Collaborations with international partners travel. and clinician researchers have published 58 like the Johns Hopkins Medical Institution, peer-reviewed journal papers, contributed to University of Texas and University of New Tan Tock Seng Hospital (TTSH), as the 12 book chapters, had 11 oral presentations South Wales have also been forged. Projects National Referral Centre for communicable and 42 poster presentations. They have examining molecular epidemiology, inter- diseases and HIV infection and for infectious trained 12 PhD, five Masters students and won subtype differences in bystander T-cell post exposure management, is also the MOH/ additional competitive research grant funding. apoptosis and the different treatments for HIV NEA designated outbreak management patients have since been conducted. centre. Research and knowledge is one of STOP dengue also marked the inaugural the pillars in TTSH’s pursuit of excellence in ASEAN dengue day on 15 June 2011 together Additionally, an NMRC-funded collaboration medical advancement in infectious diseases. with the Minister for the Environment and with A*STAR had resulted in a locally Water Resources, Dr Vivian Balakrishnan, developed HIV-1 quantitation assay which has The TTSH Communicable Disease Centre and the World Health Organisation’s Regional been successfully patented. The cost of the (CDC) aims to become a regionally and Director for the Western Pacific, Dr Shin Yong- HIV viral load test used to be a major barrier internationally recognised centre for clinical Soo. for inclusion as a routine part of clinical care. care, training and research into infectious Research done on in-house viral load assay diseases. Amongst the key research This preceded an educational dengue (2008-2009) by TTSH CDC has enabled TTSH programmes in TTSH CDC, the STOP Dengue symposium attended by the local and to have a cheaper in-house assay for TTSH programme led by TTSH CDC’s Clinical international scientific community and patients. Director, Associate Professor Leo Yee Sin, who Singapore general practitioners. In conjunction also heads the Infectious Disease department with the symposium, a public exhibition on These various research have helped to at TTSH focuses on optimising early diagnosis, dengue was also held at TTSH’s Atrium to improve the care for HIV patients. The locally prognosis and case management for adult commemorate the inaugural ASEAN Dengue developed viral load and genotypic resistance dengue infection. day, graced by Minister for Health, Mr Gan Kim test has facilitated access to these tests for Yong. our patients. The patenting of the viral load STOP Dengue Translational and Clinical kit helps to ensure continued and affordable Research (TCR) funded by NMRC since HIV research is another area in TTSH that access for our patients. December 2008 serves as the focal point for has led promising programs and achieved Dengue Research collaboration in Singapore. extensive collaborations internationally. Being Research into the molecular epidemiology It integrates established groups from Infectious the national reference centre for HIV clinical of HIV-1 in Singapore has also helped the Diseases departments of TTSH, NUS and care in Singapore, TTSH is the largest HIV identification of a novel recombinant strain, Duke-NUS to form internationally competitive treatment centre caring for 2,500 patients CRF51_01B, which was generated in programs. (70% of national patients). The CDC HIV Singapore as a result of recombination of the treatment programmes has been at the two existing strains, CRF01_AE and subtype This multi-disciplinary 5-year programme forefront of research, collaborating extensively B. These enable us to effectively manage and seeks to integrate knowledge gathered on to bring progress to HIV patient care, publish treat our patients with HIV effectively. topics such as developing optimal dengue results to contribute generalisable knowledge management strategies; understanding and patent ideas to commercialise benefits. disease pathogenesis; discovery of prognostic makers; prevention of the spread of Dengue Locally, CDC investigators are heading and effective targeted therapy. a multi-centred collaboration involvingCATALYST ACCELERATING RESEARCH

RESPONSIBLE CONDUCT OF RESEARCH education 17Responsible Conduct of Research (RCR)Conflictof Interest In the previous issues of Catalyst, we have introduced 2 out of the 8 components of Responsible Conduct of Research (RCR) – Research Misconduct and Protection of Human Subjects. In this issue, we will look at the 3rd component of RCR - Conflict of Interest.Researchers are motivated to work hard for interests can provide a strong incentive to review grant applications, publications or ethicsmany reasons - to contribute to advancing overemphasise or underemphasise research applications submitted by close colleaguesknowledge, to make discoveries that will findings or even encourage research or students that they are mentoring. This isbenefit individuals and society, to further their misconduct. Financial COI are situations that because their presumed interest in wanting toindividual professions and to achieve personal create perceived or actual tensions between see their colleagues or students succeed couldgain and satisfaction, among other reasons. personal financial gain and adherence to the possibly conflict with their obligation to make fundamental values of honesty, accuracy, objective, evidence-based judgements. Thus,While the advancement of efficiency and objectivity. most grant funding agencies as well as DSRBknowledge is best served requires reviewers to disclose any conflict ofby the sharing of ideas If a researcher and or his/her study team interest beforehand.with colleagues, legitimate (inclusive of immediate family members) hasresearch interests can create financial interests (e.g. stocks, stock options Intellectual conflicts are more difficult tocompeting responsibilities or other ownership interests in the assets or identify. If a researcher holds strong personaland lead to what is liabilities of any company that may benefit from views on the importance of a particular areacommonly called conflict of the research activity), the researcher must of research or a set of research findings (i.e.interest (COI). declare this on the DSRB Application. The If a researcher holds a strong view that bone declaration should provide a full disclosure of marrow aspiration must be carried out first toIt is important to understand that COIs are the facts giving rise to the financial interest and accurately diagnosis leukaemia in a patientnot entirely bad. In this day of research, the should detail the steps proposed to eliminate suspected of leukaemia), these views shouldcomplexity and demanding nature of research any potential conflict of interest that may arise be disclosed so that others can take them intoinevitably gives rise to competing obligations from the financial interests. consideration when judging the researcher’sand interests. Not only are researchers statement(s).expected to serve on committees, train aspiring Conflicts of Commitmentresearchers, teach, etc., they are at the same At any one time, a researcher is likely to be Likewise is true of strong moral convictionstime, expected to pursue their own research. wearing more than one hat, i.e. working on one that could influence a researcher’s scientificHowever, in the crucial areas of financial or more grant-funded projects, working as a opinions. This might be particularly evidentgain, work commitments and personal and paid employee of an institution or sitting on an when researchers serve as expert advisors (e.g.intellectual matters, it is necessary to take advisory board etc. Therefore, these activities A researcher/expert advisor who has strongappropriate measures to ensure that COIs do place competing demands on the researcher’s moral convictions against the terminationnot contest with the responsible practice of time and loyalties, leading to conflicts of of unwanted pregnancies has been taskedresearch. commitment. Special care is thus required to review a study involving tissue samples to ensure that these commitments do not obtained from foetuses prior to the terminationFinancial Conflicts of Interest interfere with one another. of the unwanted pregnancy.Personal interests and prospects of financialgain can unfortunately influence a researcher’s For example, if a researcher has two concurrent In this case, the researcher’s personalelemental obligation to truth and honesty. grant-funded studies, he/she should minimally convictions could influence scientificResearchers should not, but may find honor the time commitments made, by judgements and may therefore, bias the reviewunreasonable ways to delay a competitor’s devoting a specific percentage of his/her time outcome). Therefore, researchers shouldwork so as to secure a patent or other to either study. be vigilant and avoid making judgements orfinancial advantage for themselves. Financial presenting conclusions based solely on their Personal and intellectual conflicts opinions or affiliations rather than on scientific Personal conflicts are usually easier to identify evidence. and resolve. Generally, researchers should not ISSUE 12 JUL / AUG 2012

18 education good reference book for researchlifegiving mentors: a guide forinvesting your life in othersby Tim ElmoreAssociate Professor Sim Kang For those who have been inspired to mentor mentor to help me ask the right questionsSenior Consultant Psychiatrist or be mentored, perhaps abounding questions in research, develop a discipline to relate toDeputy Chief, General Psychiatry Department include how can I find a suitable mentor or the mentor, and to appreciate that the bestDeputy Director, Research Division mentee and what are common problems faced mentoring is “intensity in a narrow field” in theInstitute of Mental Health during mentoring. In this regard, I have found areas of learning, practice and assimilation. this book entitled “LifeGiving Mentors: A guideMost of us at various points in for investing your life in others” refreshing and The author shares many life examples whichour profession will be involved a rich resource of ideas. should allow some of the principles to stickin mentoring either in a formal better in our minds after reading them. Indeedor informal way. Some of us The author reminds us to be mindful of the the journey of research mentoring is aboutmay be a mentor to juniors in needs of the mentees that are integral to the helping our mentees through knowing, byour midst within our vocation mentoring journey and how their needs may showing, to get going and for mentees to seeand in turn be a mentee to a differ from our preconceived notions of how we their growth.senior whom we respect and were when we started that journey.aspire to emulate. This applies I have also realized that three Ps; Process,to research mentoring as well. As a mentor in the research domain, I am Preparation and Perseverance, are crucial in reminded by the author to take note of this journey, that is, the realization that first,As I reflect and contemplate on this issue of discovering the strengths of the mentee, it is a process of learning and relearning, andresearch mentoring and how to do it better, determining their focus, discerning their blind relating; second, it requires preparation inseveral questions continue to fill my mind spots, and closing the gap between potential terms of thoughtful collaborative deliberationssuch as how can I be a better influence to my and performance or output. about the content of mentoring; and lastly thatmentee (or how I can avoid passing the wrong it takes perseverance and persistence to see itvalues to my mentees), what is successful As a mentee, I need to take note that there bear fruit. Happy reading and reflecting!mentoring, how do I confront difficult issues are no perfect mentors, that I need to ask myand mentees effectively, what should bereasonable goals and so on. local training coursesNHG Research Training Calendarfor August - December 2012Date Time Training Programme Course Category Module Venue No of Seats 00:00 - 23:59 Proper Conduct of Research PC101 & Online - Basic I & III 103 100Ongoing PC102 www.elearning.nhg.edu.sg Proper Conduct of Research – Proper 3017 Aug Basic II^ Conduct of 30022 Aug Research 30 09:00 - 18:00 Proper Conduct of Research - - PC201 National University Hospital, Kent Ridge Wing, 30 Intermediate Workshop Level 2, ASTC, STLab 50 30 14:30 - 17:30 Globalisation of Clinical - Ren Ci Hospital, Multi-Purpose Hall, Level 4 Trials Forum24 Aug 13:00 - 17:45 Manuscript Writing and Research - National University Hospital, Kent Ridge Wing,14 Sep Presentation Workshop Methodology - Level 2, ASTC, STLab National University Hospital, Kent Ridge Wing, 12:45 - 17:30 Study Design Workshop Level 2, ASTC, STLab20 & 21 Sep 09:15 – 18:00 Singapore Guideline for - SG-GCP National University Hospital, Kent Ridge Wing, Good Clinical Practice Level 2, ASTC, Seminar Hall28 Sep 08:30 – 17:30 Grant Preparatory Research RM105E National University Hospital, Kent Ridge Wing, Seminar Methodology Level 2, ASTC, STLabFor registration and full details, please visit www.research.nhg.com.sg (Training & Education > Search for a Course) * Dates are subjected to changes without prior notice ^ For more information, refer to (www.research.nhg.com.sg -> Training & Education -> Proper Conduct of Research Courses)CATALYST ACCELERATING RESEARCH

UPDATES ON LOCAL REGULATIONS regulations 19Clinical Trials on Medical DevicesWhat you need to know about thecurrent controls and the new regulationsThe Health Sciences Authority will be When will the new regulations for of unregistered medical device of risk classintroducing new regulatory controls conducting clinical trials on medical devices C & D. This category of applications would befor medical devices investigated in be implemented? evaluated under the CTA system. An approvalclinical trials. A new piece of subsidiary is required from HSA before the trial canlegislation, the Health Products (Clinical The new regulatory framework will be commence. The target timeline for regulatoryTrials) Regulations, will be promulgated implemented upon the introduction of the evaluation is 30 working days.under the Health Products Act. The Health Products (Clinical Trials) Regulations.regulatory scope of this legislation will The target timeline for implementation is in the How do I apply for the import of aninclude medical devices investigated in first half of 2013. unregistered investigational medical deviceclinical studies in addition to drug trials, for clinical trials?which are currently regulated under What is the scope of the new regulations?the existing Medicines (Clinical Trials) With the full implementation of the regulatoryRegulations. The scope of the new regulations will include framework for registration of medical devices, medical devices of a higher risk class (class C import and supply of unregistered medicalHSA has adopted a risk-based approach & D) regardless of their registration status with devices is prohibited. However, import andin implementing these new requirements HSA. It will exclude medical devices of a lower supply of such devices solely for the purposeand will continue to ensure the risk class (class A & B), and “non-invasive ” of use in clinical trials can be authorisedrequirements are administered in the and “non-confirmatory ” in-vitro diagnostic by HSA. Currently, sponsors can submitleast burdensome way possible whilst products. completed applications of CTM (Medicalensuring trial participants are protected. Devices) for import of unregistered medical How will the new regulations for conducting devices for use in clinical trials.What are the current regulatory clinical trials on medical devices berequirements for conducting clinical trials on implemented? The application can be submitted in hard-medical devices? copy to HSA’s Clinical Trials Branch. Upon The new regulatory controls will be approval, an import permit number wouldUnder the current Medicines (Clinical implemented in phases to allow stakeholders be indicated on the CTM (Medical Devices)Trials) Regulations, a CTC (Clinical Trial adequate time to transit to a full regulatory application form. The approval would serve asCertificate) application is not required for framework. During the first phase, HSA will the regulatory authorisation to facilitate thestudies assessing the safety, performance administer a CTN (Clinical Trial Notification) importation of the unregistered medical deviceor effectiveness of a medical device. It system i.e. the sponsor of the clinical trials will for use in clinical trials. The authorisation ofis the sponsor’s/ principal investigator’s be required to notify HSA of their clinical trials the CTM (Medical Devices) will enable theresponsibility to seek ethics approval assessing the safety/performance of medical importer to use it for multiple imports ofto conduct the trial from the respective device of risk class C & D. unregistered medical devices for clinical trialIRB(s) (Institutional Review Boards) before purpose and is valid for 6 months from thecommencement of the trial. Upon HSA acceptance of the notification, date of approval. targeted to be within 3 working days, the trialCurrently, for all medical devices whether can proceed provided all other applicable Where can further information be obtained?they are used in routine practice or in clinical requirements such as ethics approvals andtrials, the specific regulatory requirements as contract agreements have been fulfilled. HSA had conducted a few briefing sessionsper the Health Products (Medical Devices) on the changes to the upcoming regulationsRegulations 2010 should be followed. The In the second phase, which will be the full specifically on the new controls for medicalduties and obligations of manufacturers, implementation of the regulatory framework, devices investigated in clinical trials. Theimporters or wholesalers of medical devices HSA will also introduce the CTA (Clinical Trial presentation slides used in these sessionsthat currently applies include: Authorisation) system. The CTN system will are available at the following HSA website: continue to be applicable for clinical trials http://www.hsa.gov.sg/publish/hsaportal/en/ • Reporting of defects and adverse effects to investigating registered medical devices, health_products_regulation/clinical_trials/ HSA i.e. devices listed on the SMDR (Singapore industry_communication.html Medical Device Register). • Notification to HSA concerning recall There will be more regulatory briefing sessions • Duty to maintain records of supply Sponsors of clinical trials will be required to for stakeholders in Q4 of 2012. So stay tuned! • Duty to maintain records of complaints submit regulatory applications to HSA for • Labelling requirements clinical trials assessing the safety/performance ISSUE 12 JUL / AUG 2012

20 regulations UPDATES ON LOCAL REGULATIONSUpdates from NHG Domain Specific Review Board (DSRB)Conditionally Registered Doctors as Principal Investigators in ResearchA Principal Investigator (PI) must be qualified For research proposals submitted to the NHG ● For less than minimal risk research studies,by education, training and experience to Domain Specific Review Boards (DSRB) Level 2 Conditionally Registered doctors areassume responsibility for the proper conduct for ethics review, NHG DSRB now allows allowed to be Principal Investigators; andof a research study and should meet all Conditionally Registered doctors of Levels 2qualifications specified by the applicable and 3 supervision to be Principal Investigators ● For more than minimal risk research studies,regulatory requirements. of research studies according to the level of Level 3 Conditionally Registered doctors risk, as follows: allowed to be Principal Investigators. Additional conditions required to be fulfilled:No. Conditions Less than minimal risk studies More than minimal risk studies1 Doctor’s Profile The doctor must be at Level 2 supervision – i.e. After The doctor must be at Level 3 supervision – i.e. After 0.5 years at Level 1 and received at least “above av- 0.5 years at Level 1 and received at least “above erage” performance grading for the past 6 months. average” performance grading for L1, and after 1.0 year at L2 and has been ascertained to be ready to work independently, but have yet to fulfill the specified period of supervised practice required for computation towards Full Registration.2 Commitment of PI’s supervisor must declare in writing that: Supervisor a. She/he is aware of, and supports, the involvement of the Conditionally Registered doctor as PI b. She/he will provide guidance and include research activities in regular progress reports to SMC c. Based on the doctor’s current progress and technical and ethical competency, the Conditionally Registered doctor is deemed competent to assume the role of PI and affirm that the Conditionally Registered doctor has adequate medical expertise to provide medical care and make medical decisions for safety and welfare of the subjects3 Declaration to SMC PI declares that his involvement in research as PI has been provided to SMC and no objection has been received from SMC.4 DR/IR Approval Department Representative and Institutional Representative approve the Conditionally Registered doctor to be PI.All written documentation (Items 1-3 in the table above) should be attached to the DSRB Application, for DSRB’s consideration in the review of the study. The endorse-ment of the online application on ROAM by the Department Representative and Institutional Representative will be considered proof that Item 4 has been fulfilled (i.e. noseparate written documentation required).For more information, please contact DSRB at +65 6471 3266 or [email protected] New Templates:Investigator File DividersA common question asked by investigators, particularly those new to research, is how to createand maintain Essential Documents required for a study. The Singapore Guideline for Good Clinical These documents serve to demonstrate the Investigator File Dividers template to help Practice (SG-GCP) defines Essential compliance of the investigator, sponsor and investigators who are conducting Investigator- Documents as documents which individually monitor with the standards of SG-GCP and all Initiated studies maintain proper research and collectively permit evaluation of the applicable regulatory requirements. To assist documentation and adhere to high standards conduct of a trial and the quality of the data investigators in creating and maintaining these of practice in the conduct of human subject produced. Essential Documents, NHG has created the research.CATALYST ACCELERATING RESEARCH

UPDATES ON LOCAL REGULATIONS regulations 21(continued from previous page)The Investigator File Dividers template has been added tothe existing templates available for download on the NHGresearch website. Besides its primary function to indicate andseparate the main sections required in an Investigator File, thedividers of each respective section also provide elaborationon the types of documents to file in each section and listimportant notes and links to the relevant guidelines for theinvestigators’ easy reference. The File Dividers templates arecategorized into ‘PI-Initiated Clinical Trials (involving Drug/Device)’ and ‘Clinical Research (not involving Drug/Device)’with the respective sections below.Investigator File Dividers Investigator File Dividers(For PI-Initiated Clinical Trial involving Drug/Device) (For Clinical Research not involving Drug/Device)● Study Team ● Study Team● Study Documents ● Study Documents● Institutional Review Board Documents ● Institutional Review Board Documents● Regulatory Documents ● Study Logs and Signed Informed Consent Documents● Study Logs and Signed Informed Consent Documents ● Laboratory & Biological Specimen● Safety Reports ● Financial Documents● Investigational Product ● Other Documents● Laboratory & Biological Specimen● Financial Documents● Other DocumentsDo log on to the NHG Research Website (www.research.nhg.com.sg --> resources) to take a look and utilize this new template for your study soon!Organised by: In collaboration with: In conjuction with: Asia Pacific Society of Ophthalmic Plastic & Reconstructive Surgery For more details, please contact Congress Secretariat at:Tel : (65) 6357 7735 | Fax : (65) 6357 7649 | Email : [email protected] | Website :ISwSwUEw12.tJeUi.Ln/hAgUG.c2o0m12.sg DISCLAIMER: NATIONAL HEALTHCARE GROUP EYE INSTITUTE 5TH INTERNATIONAL OPHTHALMOLOGY CONGRESS HAS NO RELATION NOR AFFILIATION WITH INTERNATIONAL CONGRESS OF OPHTHALMOLOGY’S WORLD OPHTHALMOLOGY CONGRESS.

22 money LOCAL GRANTS / AWARDS RECEIVEDNational Medical Research Council(NMRC) Research Training Fellowship 2011The NMRC Research Training Fellowship is awarded to outstanding and talented clinicians, health science professionals(e.g., nurses, pharmacists) and biostatisticians for overseas research training or to pursue a graduate degree in researchin local institutions. Two of our staff have been awarded the NMRC Research Training Fellowship. Lam Zhan Yang, Max Research Psychologist, Research Division, Institute of Mental HealthAbout Finding the Unknown Personal ReflectionsMax had a head start by working as a student Max’s PhD training with the Department of The NMRC research fellowship award wasresearch assistant at National University of Psychological Medicine, Yong Loo Lin School very competitive and Max was pleased andSingapore (NUS) during his undergraduate of Medicine, NUS started in August 2011, grateful to be awarded it. It was a key enablerdays. Research had always been an important under the National Medical Research Council for him to pursue his PhD training and madepart of his life because he was interested to (NMRC) Fellowship Award. The title of his him more determined to push the envelope ofknow why people behaved and experienced thesis is “Elucidating the Genetic Architecture innovation and science harder, in an attemptfeelings in certain ways. of Neuropsychological Performance”. The to make breakthroughs in research that will set project investigates the genetic make up Singapore’s psychiatry and psychological R &When psychological illness struck close of neuropsychological abilities and tries to D on the international stage.to home, it crystallised to him a desire to understand whether they are genetic in nature.know more, to generate more knowledge He is extremely thankful to many people andso that sufferers can be better understood We commonly find ourselves trying to mentors who helped him throughout theand therefore, treated differently. He began remember someone’s telephone number or journey. Max believes that embarking on PhDhis career in mental health research after address, pay attention in speeches or lectures, training is an essential step in becoming agraduation in 2008. and make complex decisions in our day to scientific investigator. At the same time, it is day work. These are basic neuropsychological also a decision that will impact one’s careerMax was trained and mentored by experienced domains and previous twins and family studies and family life.clinicians and researchers such as Professor suggest that cognition appears to be heritable.Opler, Professor Michael First and Professor To him, it is time and energy invested intoRichard Keefe. He feels privileged and Capitalizing on the advances in genetic generating new knowledge: Knowledge thathonoured to learn and to be able to contribute microarray technologies, the thrust of his has the potential to make someone else’sback to the field by being involved in the research is to refine the cognitive behavioural world a slightly better one. He believesSingapore Translational Clinical Research measures that have been collected as part of research is an ideal, a belief, a passion and anProject (STCRP) as a researcher. the STCRP in healthy participants. identity – all of which is lifelong. The scientific and inquisitive mind never really retires.Being a neuropsychological tester and clinical Thereafter, a scan of the human genome willrater allowed him to spend more time with be conducted, to identify strong associations For people wanting to follow this path ofpatients and provided glimpses of the world with certain genes. He believes that this work research, he says, “persistence and patiencethe patients live in. will support the many cognitive and behaviour have been in the equation for me. Bite the genetics work investigating pathological bullet, don’t give up.” cognitive processes in mental illnesses.Goh Tze JuiSenior Psychologist, Autism Services, Department of Child and Adolescent Psychiatry, Institute of Mental HealthAbout (ASD) who may present with co-morbid mental the Autism Diagnostic Observation ScheduleTze Jui joined IMH in 2006 and is currently a health issues, in terms of individualised and and is part of the multidisciplinary assessmentSenior Psychologist with the Neurobehavioral group sessions as well as in a collaborative team at Autism Clinic.Clinic under Child Guidance Clinic, Department format with parents/caregivers and schoolsof Child and Adolescent Psychiatry, Institute of with regards to education and supportive work. As part of her job, she often participates inMental Health (IMH). sharing or mentoring sessions with colleagues, She is trained in the administration of fellow professionals and students throughShe works primarily with children and standardized assessments instruments such as sit-ins and observation sessions. She is alsoadolescents with an Autism Spectrum Disorder the Autism Diagnostic Interview – Revised and active in research projects on ASD and hasCATALYST ACCELERATING RESEARCH

LOCAL GRANTS / AWARDS RECEIVED currently in the planning and conceptualisation money 23 stage but aims to apply a clinical psychological(continued from previous page) focus in the management of ASD in Although she has just started her journey of Singapore. Fellowship training and doctoral studies, sheassumed the roles of Principal Investigator and feels that the award has provided her with aCollaborators by initiating studies and working Being of a New Challenge new outlook on the landscape for professionaljointly with other organizations. Tze Jui feels that the fellowship award development in the field of psychology in is an encouragement for her and is an Singapore.Learning and Working at the Same Time acknowledgment of the valuable contributionTze Jui is currently pursuing her doctoral of Allied Professionals in research areas. The It is a strong motivator in encouraging fellowstudies in Clinical Psychology at James support from IMH and her mentors allows her colleagues and juniors from Allied HealthCook University, Singapore, supported by a to initiate research in important clinical areas professions to participate in research andFellowship Award from the National Medical and also bridges collaboration with external other areas of clinical work. She encouragesResearch Council Singapore. She chose to agencies who are also important stakeholders practicing psychologists to adopt a clinician-pursue an accredited local degree to being, as in fields of clinical psychology and areas scientist model in their work, which willphysically present in Singapore allows her to related to ASD. provide them with the tools and skill sets tocontinue her on-going research work at IMH. engage in evidence-based practice.Her thesis focuses on ASD which is anarea she is passionate about. The project isRESEARCH TRAINING FELLOWSHIP 2012Dr Rupesh Agrawal MMed, FRCS (Glasg), FAMS, Associate Consultant, NHG Eye Institute, Tan Tock Seng HospitalDeveloping a molecular-targeted fluorescent probe as thebasis for a human retinal leukogram to image the progressionof Intraocular Inflammation and Diabetic Retinopathy2 year full-time fellowship/training leading to a Doctor of Medicine (Research) at University College London (UCL), UKExperimentation in numerous animal models the live assessment in the animal retina of peptide candidates for their ability toof retinal vasculopathy and several lines leukocytes in diabetic, inflammatory and specifically bind human leukocytes in vitro andof clinical evidence support the concept angiogenic disease, into a potential biomarker to select a lead candidate fluorescent peptidethat chronic, subclinical leukostasis and and diagnostic tool to monitor the onset and conjugate for further development based onsubsequent downstream inflammatory progression of DR & intraocular inflammation the ability to detect leukostasis in the livingprocesses within the retina are central to the in humans, as well as an essential enabling rodent retina following systemic administrationonset and progression of diabetic retinopathy tool for the development of novel treatments. using scanning laser ophthalmoscopy (SLO).(DR). The technique would consist of a fluorescent Once Dr Rupesh completes his dissertationSimilarly, intraocular inflammation requires probe administered systemically to bind on Human retinal leukogram and gets hislong term immunosuppressive therapy which intravascular leukocytes, and within minutes Doctor of Medicine in Research, the teamrequires to be monitored based on extent of routine fluorescence ophthalmoscopy will will compete for further funds from BMRC orcellular reaction in the retina, vitreous and reveal the number of inflammatory cells in the NMRC to complete preclinical developmentaqueous humor. retina—similar to the process for fluorescein and initiate Phase 1 studies which should angiography. provide a safety evaluation and initial proof-In this project, Dr Rupesh under mentorship of-concept data in collaboration with A*Star,of Prof David Shima at UCL would aims to The aims of this proposed research are to IMRE and Singapore Eye Research Institutetransform a well-accepted research tool, characterize and evolve several fluorescent locally in Singapore.TTSH Pitch-For-Fund ProgramTTSH had launched the inaugural TTSH Pitch-For-Fund Program on 1 September 2011.The aims of the exercise is to enable TTSH staff to quickly obtain some monies for a small research project so that they can present theirpreliminary data when they apply for a grant at the national level. The judging consists of two steps. First, the applications are read by a groupof judges drawn from the Hospital’s Clinical Research Committee. Shortlisted candidates are then asked to present to a panel of judges,without any presentation slides. Two of the judges are non-TTSH.In the first TTSH Pitch-For-Fund Program in 2011, there were 5 awardees being granted $10,000 for a period of one year. Congratulations tothe 5 Awardees - Dr Tan Ern Yu and Dr Pek Chong Han from General Surgery, Dr Rupesh Agarwal and Dr Melissa Tien from Ophthalmologyand Dr Stephen Chan from Anaesthesiology. ISSUE 12 JUL / AUG 2012

24 money Major Research Funding Available Upcoming Grant Calls in SingaporeNational Medical Research Council (NMRC) Grants http://www.nmrc.gov.sgGrant Name Grant Description Funding Quantum Application DateClinician Scientist – The CS-IRG is provided to Clinician Scientists to Maximum of S$1.5 million per pro- 1st Nov 2012Individual Research Grant (CS-IRG) enable them to carry out medical research on a ject for 3 years with additional 20% 1st Nov 2012Clinician Scientist – specifically defined topic. All CS-IRG applications indirect costs. 1st Nov 2012Individual Research Grant – will be evaluated through a two stage process with 1st Nov 2012New Investigator Grant (CS-IRG-NIG) an international peer review stage followed by a Maximum of S$200,000 per project 1st Nov 2012Cooperative Basic Research Grant Local Review Panel. for 2 years with additional 20% 1st Nov 2012(CBRG) The CS-IRG-NIG is a subcategory of the CS-IRG to indirect costs.Cooperative Basic Research Grant - cater for new clinical investigators. The CS-IRG-NIG Maximum of S$1.5 million per pro- 1st Nov 2012New Investigators Grant (CBRG-NIG) is a step for the new investigator to a first independ- ject for 3 years with additional 20%Transition Award (TA) ent national level grant. indirect costs. The CBRG is provided to non-clinical researchersClinician Scientist Award (CSA) to conduct research proposals in basic and Maximum of S$200,000 per project translational clinical research. The CBRGs also for 2 years with additional 20%Health Services Research - aims to promote basic biomedical sciences (BMS) indirect costsCompetitive Research Grant – research collaborations across institutions in Maximum of S$375,000 per awardNew Investigator Grant (HSR-CRG-NIG) Singapore. for 3 years with 20% indirect costs The CBRG-NIG Is a subcategory of the CBRG to cater for new non-clinical investigators. The Investigator Category: CBRG-NIG is a step for the new investigator to a first Maximum of 3 years’ salary support independent national level grant. and grant support of S$675,000 for 3 The TA is provided to assist budding, young clini- years with 20% overhead costs. cians who have just returned from formal research Senior Investigator Category: training, to build up their capability in research. It Maximum of 5 years’ salary support includes funding support for mentored research and grant support of S$1.75 million project with salary and grant funding for up to three for 3 years with 20% overhead costs. years. As HSR-CRG-NIG is a new grant in The CSA aims to provide salary & funding sup- 2012, more information on the fund- port for selected outstanding clinician scientists, ing quantum will be provided nearer who possess a consistent record of excellence in to the grant call research, to enable them to carry out internationally competitive translational and clinical research. The HSR-CRG is a MOH research grant established in promote the conduct of HSR and enable the translation of HSR findings into policy and practice. The HSR-CRG-NIG is a subcategory of the HSR- CRG to cater for new investigators. The HSR-CRG- NIG is a step for the new investigator to a first independent national level grant.Agency for Science, Technology and Research (A*STAR) Grant http://www.a-star.edu.sgGrant Name Grant Description Funding Quantum Application Date 4th Biomedical Engineering Programme The BEP is provided to foster Clinician-Engineer Estimated at between S$250,000 Dec 2012 (BEP) Grant Call collaborations for development of medical devices and S$500,000 for up to 3 years.CATALYST ACCELERATING RESEARCH and solutions to clinical problems. In particular, it supports collaborative research projects with emphasis on devices, procedures, diagnosis, and clinical systems to improve patient care and cost- efficiency of the healthcare system. Note: More information on the application date will be provided nearer to the grant call

Major Research Funding Available money 25NHG Intramural Grants http://www.research.nhg.com.sgGrant Name Grant Description Funding Quantum Application DateClinician Leadership in Research (CLR) 1st Oct 2012 The CLR is a 2 year programme that consists of 3 Maximum of S$5,000 per year components: Mentorship, Training and Assessment. with additional S$500 academic Successful applicants will explore collaborative op- allowance for up to 2 years. portunities with their nominated mentors and receive seed funding and academic allowances to support these research projects.Small Innovative Grant (SIG) The SIG aims to fund clinically relevant research Maximum of S$50,000 per year 1st Oct 2012 projects that can contribute directly to improve for up to 2 years. patient care or to enhance clinical research capabilities in NHG. It is designed to support exploratory and innovative studies with the aim of preparing young investigators to initiate larger investigations and vie for competitive grants on a national level.In FocusNew NHG Grants 2012 - NHG Clinician Scientist CareerScheme (CSCS) & NHG Thematic Grant (NTG)National Healthcare Group Research & Development Office (RDO) has successfully launched the new NHG ClinicianScientist Career Scheme (CSCS) & NHG Thematic Grant (NTG) for 2012. We are pleased to introduce the 2 new NHGgrants in this Catalyst issue, and be sure to catch the next issue for the list of successful applicants!About NHG Clinician Scientist Career Scheme (CSCS) Institute of Mental HealthThe NHG CSCS call for applications started on 9 April 2012 and has received Participate in Oura total of 8 applications. NHG CSCS’ short term aim is to develop research Research Studiescapabilities of our clinicians to enable them to compete successfully forNMRC’s Transition Award (TA) or Clinician Scientist Award (CSA) in the next The Research Division of Institute of Mental2-3 years. The longer term aim of the scheme is to develop clinician scientists Health carries out scientifically and clinicallywho will contribute to excellence in research innovation and improvement in relevant research to help us to understandpatient care, delivery and outcomes. the mechanisms underlying various mental disorders and translates these findings intoThis scheme also provides a customized research career development path interventions for better patient care. Wefor all clinicians in NHG who are interested in embarking a career in research are currently recruiting participants for twoimmediately or in the near future. Besides research funding, successful research studies:applicants will enjoy the benefit of having mentorship by renowned facultymembers and support by the various programs under NHG RDO to facilitate Longitudinal Youth At-Risk Studytheir research. Clinicians may apply under the Junior or Mid-Level ClinicianScientist category. The Junior category is open to AST, Registrars, Senior Longitudinal Youth At-Risk Study (LYRIKS): this study is aResidents or equivalent and Mid-Level category is open to Associate Consultant community based participatory research study that aims tos and above or equivalent. Successful applicants would receive up to 0.4FTE identify key genetic, biological, cognitive, clinical, and socialsalary support, as well as up to S$180,000 (for Junior category) and S$300,000 risk factors for serious mental illness.(for Mid-Level category) for research support over a maximum of 3 years. Singapore Mental Health Study on the ElderlyAbout NHG Thematic Grant (NTG) Well-being of the Singapore Elderly (WISE): The projectThe NTG grant call opened on 4 July 2012. Applicants were required to submit aims to establish the prevalence of dementia in Singapore andthe Letter of Intent (LOI) by 25 July 2012 and the full research proposal by 3 investigate the risk factors, service use and cost of care for theOctober 2012. The aim of this grant is to build up NHG’s research capabilities in illness. Caregivers’ burden and needs for dementia care willprogrammatic areas in order to compete successfully for NMRC’s Translational also be assessed in this nation-wide study.Clinical Research (TCR) or equivalent. Please visit www.imh.com.sg to find out how you canThis grant aims to facilitate the discovery and application of basic science ideas participate.relevant to the advancement of health, and to provide productive platformsfor collaborations within and outside NHG. Potential applications should also ISSUE 12 JUL / AUG 2012include research projects which span from bench to beside. NTG is open to allclinicians in NHG who possess a strong research track record in translationalclinical research. Successful applications will receive up to S$1 million overthree years, with a maximum of three sub-projects.

26 grapevine Have a question AUNTY RESEARCH AGONY HOW DO YOU regarding research? FORMULATE A Drop us a note at the researchtraining@nhg .com.sg and we’ll have it answered by experts in upcoming editions! Here’s one from our readers.Research QuestionPradeep Paul George, Senior Research Analyst, Health Services & Outcomes ResearchEvery research starts with a question. The and peer inputs. You could provide an angle for your researchsuccess of any research process relies, in part, through insights stemming from your personal experience,on how well investigators are able to translate contemporary issues and engagement with literature anda clinical problem into a research question—a guidance from mentors / peers. Narrowing, clarifying andtask that is not so simple. even redefining your questions are also part of the iterative process of research question development.What is a research question?A research question is a statement that identifies the Ask yourself the 5W’s (Who, What, When, Where and Why).phenomenon to be studied. A good research question A strong research idea should pass the “so what” test. Thinkdefines the investigation, sets boundaries and provides about the potential impact of the research you are proposing.direction for data collection and analysis. Developing a What is the benefit of answering your research question?researchable question can be challenging if you do not Who will it help (and how)? If you cannot make a definitiveknow what you really want. Remember: “A question well- statement about the purpose of your research, it is unlikely toasked is a question well-answered” be funded.Where to start? Research directions are not always at the full discretion ofForming and framing the right question should be seen the research. Be mindful of the practicalities, appropriatenessas an iterative process that is well informed by literature of the topic, and the ability to get peer/ mentor and funding support.How to frame the research question?The PICO approach • The patient, population, or conditions of your interest.Problem The • This could be, for instance, a treatment or diagnostic test, a prognostic factor, or an exposure.Intervention • This is usually an alternative intervention with which to compare the intervention of interest. • In studies of treatment effects this will usually be a comparison with accepted standard therapy - Acomparison or if no such therapy exists then with placebo.The outcome • This could be, for example, pain relief, quality of life or survival. of interest • Defining the outcome precisely is critical as sample size for the research study and statistical methods are determined by this. PICO Elements A well-structured research question should usually contain four parts and Patient Adults be contained within a single sentence. The process of framing a research question can be summarized by remembering the acronym PICO - Problem, Intervention Binge drinking Intervention, Comparison and Outcome. Comparator No Binge drinking Example: In adults, is binge drinking compared with no binge drinking associated with an increase in mortality? Outcome MortalityCATALYST ACCELERATING RESEARCH

grapevine 27What are the characteristics of a good research question? “FINER” the betterThe FINER criteria state that a research question must be feasible, interesting, novel, ethical, and relevant. When you think you mayhave a good idea/ question, apply the “FINER” criteria to it to see if the question is good enough.Components QuestionF - Feasible Is the question answerable? Do you have access to all the materials you will need to do the study? Do you have access to enough subjects? Will you have enough time and money? Do you have the expertise to do this study or can you collaborate with someone who does?I - Interesting The question has to be interesting to the investigator, but should also be interesting to others.N - Novel Has this study been done before? Does it add to the current body of medical knowledge?E - Ethical Can the study be done in a way that does not subject subjects to excess risks? Will an IRB approve the study?R - Relevant Will it further medical science? Will the results change clinical practice, health policy or point towards further avenues of research?If your question fails on any one of these 5 criteria, it is probably not worth putting much effort into.ConclusionIt is hard to formulate a good answer to a bad question, so spending time on formulating and refining an interesting, important, well-structured, ethical, and practical research question is worthwhile. It will influence the choice of study design, the interpretation ofresults and the writing-up of the research report.References• O’Leary, Z. (2004) The Essential Guide to Doing Research. London: Sage. Chapter Three• Posing the research question: not so simple. [Can J Anaesth. 2009] - PubMed - NCBI [Internet]. [cited 2012 Jun 18]. Available from: http://www. ncbi.nlm.nih.gov/pubmed/19247780• Research questions, hypotheses and objectives [Internet]. [cited 2012 Jun 18]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2912019/• Guyatt, Gordon, et al. Users’ Guide to the Medical Literature. 2nd ed. New York: McGraw Hill, 2008.To find out more information on health services research, please visit www.hsor.nhg.com.sg or email [email protected] yourself certified with a nationally recognisedStatement of Attainment (SOA) upon successful completion ofProper Conduct of Research – Basic II (PC102)! As a Singapore Workforce Development Agency (WDA) Approved Training Organisation What are the benefits for the trainees? (ATO), National Healthcare Group (NHG) Research & Development Office (RDO) will be able to conduct Clinical Research training under the Clinical Research Singapore • Enhanced Module Curriculum: Face-to-face Workforce Skills Qualification (WSQ) framework and issue nationally recognized WSQ workshop and assessment reinforce acquisition of certificates. The accreditation is a testament to the quality of NHG’s training, and its ability information to deliver industry validated and endorsed competency-based training. In March 2012, the Proper Conduct of Research – Basic II (PC102) module was • Guide for career progression pathway: SOA certifies successfully accredited under the WSQ system for Clinical Research. The PC102 module that you have effectively demonstrated transferable is equivalent to the “WSQ Perform Recruitment and Retention of Subjects in Clinical skill sets of industry standards Trials” Competency Unit. This revised PC102 module consists of online lectures, a trainer- led classroom workshop and an on-site assessment. Upon successful completion of this • Self-Directed Learning: Online lectures make module, trainees receive both a “Statement of Attainment” (SOA), as well as a “Certificate learning convenient at your own time and pace of Achievement” issued by WDA and NHG respectively. • WDA Funding Subsidies: for Singaporeans andTo find out more about the course, please visit www.research.nhg.com.sg Singapore Permanent Residents (PR)(Training and education>Course Categories>Proper Conduct of Research Courses) *(Eligibility Criteria Apply) ISSUE 12 JUL / AUG 2012

28 & 29 Septemper 2012 | Max Atria@Singapore ExpoCome and Join the Medical and Scienti c Congress of the Year We have an exciting line-up of scienti c programmes with a panel of distinguished local and international speakers over the 2-day congressMedical Specialties &Clinical Services Cardiovascular Medicine Disease Management Geriatric Medicine Infectious Diseases Primary Care Forum 2012 Psychiatry RadiologyEducation Health Professions Education Nursing – Education & Innovation Simulation & Integrated Medical TrainingQuality Nursing – Quality & Safety NHG Quality Convention 2012Research Health Services Research Research – Measuring Health Utility Research – How Not To Do ResearchOrganised by: Closing Date for Registration: 2 September 2012 Visit www.shbc.com.sg for more information Participating institutions: