Mainstreaming May Improve Access to Ovarian Cancer Genetic Testing in Malaysia

By Ms. Yoon Sook Yee, Cancer Research Malaysia

Mainstreaming may improve access to ovarian cancer genetic testing inMalaysia and help identify mutation carriers who may benefit from risk management and targeted treatment, suggests preliminary results of the MaGiC Study presented at the ESMO Asia 2018 Congress.

“Screening for BRCA1and BRCA2mutations is recommended for all patients with non-mucinous ovarian cancer,” said lead author Ms Sook-Yee Yoon, Genetic Counsellor, Cancer Research Malaysia, Subang Jaya, Malaysia. “Genetic testing identifies mutation carriers and triggers appropriate risk management and treatment. In Malaysia BRCAgenetic testing and counselling is only available at specialised centres in Kuala Lumpur but most people live outside the capital.”

TheMainstreaming Genetic Counselling for Genetic Testing ofBRCA1andBRCA2in Ovarian Cancer Patients inMalaysia (MaGiC Study) was set up to: 1) assess the prevalence of germlineBRCA1andBRCA2mutations amongovarian cancer patients; 2) determine the feasibility of mainstreaming of genetic testing and counselling at local hospitals; and 3) examine the psychosocial impact of genetic testing in Malaysia.

The study was designed to recruit 800 ovarian cancer patients over a three-year period. Basic genetic counselling workshops were held for 60 non-genetic clinicians from 25 hospitals across Malaysia. Patients are counselled by a trained non-genetic clinician in their local hospital in a clinical programme led by Professor Yin Ling Woo, MaGiC’s lead clinician, or by a genetic counsellor or clinical geneticist in a programme led by Professor Meow Keong Thong, who is the lead clinical geneticist at specialised centres in Kuala Lumpur.

All blood samples are analysed for BRCAmutations by Cancer Research Malaysia, led by Dr Joanna Lim who is the diagnostic lead. Patients receive pre-test counselling, followed by test results and post-test counselling. After both pre-and post-test counselling they are interviewed by a study researcher over the telephone to assess feasibility and the psychosocial impact of the experience. Interviews are based on scales adapted for use in Malaysia, including the Genetic Counselling Satisfaction Scale, the Decisional Conflict Scale, the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, the Distress Thermometer, and the Cancer Worry Scale. Interview results are being compared between the two counselling processes.

Two years into the study 476 patients have been recruited, of whom 445 received genetic testing and 59 (13%) had BRCA mutations.

“Around 13% of those tested were BRCAmutation carriers which is quite similar to that found in other populations,” said Yoon. “We found carriers throughout the country and are working with local clinicians to establish protocols in local hospitals that have not managed patients with known BRCAmutations before, thus building capacity in multidisciplinary teams for high risk management of breast and ovarian cancer risk.

In terms of feasibility, patients in the local and specialised counselling arms were equally satisfied with the counselling they received. The local counselling arm has been recruiting patients more quickly than the specialised arm. Yoon said: “Patients seem to prefer local appointments, so if they are referred to another centre for genetic counselling, they seem less likely to attend.”

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Preliminary results show that the answers to the psychosocial surveys were similar between the two groups. Mostpatients were satisfied with their counselling experience, felt informed about their choices, and found it easy to decide to go ahead with genetic testing. Yoon said: “These are preliminary results but mainstreaming of genetic counselling in Malaysia may be a feasible model to improve access to genetic testing services or patients with ovarian cancer. If successful, this model could be adopted for other cancers and in other parts of Southeast Asia.”

“Cancer is still a taboo subject in Malaysia and there is a fatalistic attitude to hereditary conditions,” continued Yoon. “Genetic information can cause conflict in families and the data we are collecting on the psychosocial impact of genetic testing will provide insights into the psychosocial challenges. With this knowledge, we can focus on interventions to overcome these challenges.”

In addition, in the past, genetic testing in ovarian cancer was limited to a small number of patients with the aim of identifying relatives at risk. Now that there is a drug that can potentially treat cancer patients with BRCAmutations, genetic counselling and testing may be requested by many more patients with epithelial ovarian cancer. This may increase the number of patients who qualify for testing and specialised centres may become overloaded.

 

Hepatitis C Elimination Through Access to Diagnostics (Head-Start) Comes to Malaysia!

Q&A with Sonjelle Shilton, Project Manager for the HCV Programme

 

Sonjelle Shilton, Project Manager for the HCV Programme

I joined FIND in 2017, and took on the role of Project Manager for the Hepatitis C Elimination through Access to Diagnostics (HEAD-Start) project earlier this year. The majority of my career has been in Africa, where I spent 10 years as the Director of Operations of a community-based health outreach organization, HardtHaven, in rural Ghana – which showed me how critical it is that public health interventions be collaboratively designed and implemented with rigorous and meaningful data capture. If you don’t measure it, you can’t see if it’s making an impact. I brought my experiences from Ghana to the monitoring and evaluation team at Gavi, the Vaccine Alliance, where I coordinated multi-country, multi-year, prospective full-country evaluations before joining FIND. I hold a Master of Global Public Health and the Global WACh Graduate Certificate in Integrated Health of Women, Adolescents and Children from the University of Washington, USA.

Can you tell us a little more about FIND? Why are diagnostics so important?

FIND is a global non-profit organization that drives innovation in the development and delivery of diagnostics to combat major diseases affecting the world’s poorest populations. It is astounding to see how often diagnostics do not exist, are inaccessible, or cost too much. This needs to change: not only do diagnostics tell patients what is wrong with them, they allow patients to be linked to the right treatment. Plus they are essential to a fully functional health system for many reasons, including surveillance to detect disease patterns and inform public health decisions. Diagnostics also play an important role in the research and development of drugs and vaccines.

 

What is the HEAD-Start project all about?

Hepatitis C is an emergency – 4 out of 5 people with the virus are unaware that they have it, and the mortality rate is rising. Diagnostics exist but they are generally limited to specialist laboratory use, and not getting to the people who need them. A complicating factor is that hepatitis C predominantly affects at-risk or marginalized populations, like people living with HIV, and those who inject drugs. Our HEAD-Start project, funded by Unitaid, is working to improve diagnosis of hepatitis C by simplifying the testing process and making diagnostics more affordable and more widely available. We’re aiming to generate data that will help to drive a change in global implementation guidelines and national policies in support of the World Health Organization elimination targets for 2030.

 

Malaysia has declared hepatitis C to be a national health priority. How is HEAD-Start contributing to Malaysia’s efforts to tackle this disease?

The Malaysian government is showing the world how to tackle hepatitis C – we believe Malaysia should be a model and source of inspiration that other countries in the region can look to as they scale up their own HCV responses. It was therefore really important for us to include Malaysia in HEAD-Start, and it is the only high-middle-income country covered by the project. Earlier this year we signed a Memorandum of Understanding with CRM to collaborate in the research and development of an innovative hepatitis C diagnostic testing strategy that we hope will lead to more cost efficient and earlier detection of hepatitis C.

 

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Can you elaborate on the diagnostic challenges for hepatitis C?

In many countries, including Malaysia, health services are largely centralized – which broadly speaking means diagnostic services for hepatitis C are available in hospitals or laboratories, but not at the primary care level or in community healthcare settings where people first access health services. HIV testing sites offer some of the most accessible testing services, and we believe that integrating hepatitis C diagnostics into this existing infrastructure could be a game-changer for reaching people with hepatitis C/HIV coinfections, in addition to those who inject drugs.

 

What does that mean in practice? How will you make tests available in primary healthcare settings and what will happen to those who get a positive diagnosis?

We are working to demonstrate the feasibility of using new, rapid diagnostic tests in decentralized primary healthcare facilities, and provide technical assistance to the Malaysian Ministry of Health for their implementation. This work is being conducted in partnership between FIND and the Drugs for Neglected Diseases initiative (DNDi). Both FIND and DNDi are product development and delivery partnership organizations, so it’s in our DNA to value collaboration on projects that facilitate equitable development along the entire care cascade. People who test positive for hepatitis C will be offered treatment in one of two ways. They can either join an ongoing DNDi clinical trial, which is co-sponsored by the Malaysian Ministry of Health and designed to assess the efficacy and safety of a new, alternative treatment regimen combining sofosbuvir with the investigational drug ravidasvir. Initial results from the first stage of this trial have indicated extremely high cure rates, including hard-to-treat cases. Alternatively, they will enter the Malaysian national hepatitis C programme, which now offers free treatment (sofosbuvir/daclatasvir) in 22 government hospitals.

Journey to success in Phase 1b Clinical Study for Hepatitis B at the University Malaya Medical Centre, Malaysia

By Chan Wei Quan, Site Manager, Global Clinical Operations (GCO) Malaysia, Janssen

Prof Rosmawati and her team, together with CIC and Janssen representatives.

If you were diagnosed with chronic hepatitis B, would you be willing to try an experimental compound developed by a world-renowned pharmaceutical company? On one hand, you may be hesitant but on the other, you may want to know more about it. For novel compounds to be approved for use in the market, pharmaceutical companies go through a period of pre-clinical and clinical phases to evaluate the compound’s effectiveness. To achieve this, volunteers are needed!

Based on statistics generated by Clinical Research Malaysia (CRM) on phases of clinical trials that were conducted in Malaysia for the year of 2017, Phase 3 studies topped the chart. Whereas for Phase 1 studies, a total of 5 Phase 1b studies were conducted in Malaysia. Is Malaysia too reserved in exploring Phase 1 studies? As a matter of fact, Malaysia has recently released a Phase 1 clinical guideline as well as a Phase 1-unit inspection and accreditation program. Malaysia is now one step closer to conducting more first-in-human (Phase 1) research. Thanks to the groups of regional key opinion leaders in initiating the Phase 1 realization project (P1RP), afflicted patients in Malaysia now have access to new treatment options and regimens. Furthermore, this allows room for economic growth as clinical research could be one of its main drivers as mentioned by the previous Malaysian Health Minister, Dr. Subramaniam. A little elaboration on what Phase 1 study is. Phase 1 study is to primarily to determine what dosage is safe and how treatment should be given. Dosage may be given in single ascending dose/multiple ascending dose. The target population is usually healthy volunteer and study is conducted in small scale. You may search for “Phase 1” to know more……

Chronic Hepatitis B (CHB) is one of the most alarming diseases that has captured the attention of the public health globally. One of the common infections by the hepatitis virus, CHB is often linked with major psychosocial issues due to social stigma. In Malaysia, a multicultural country in Asia, the CHB carries rate varies depending on ethnicity and gender. According to Raihan R (2016), CHB accounts for more than 80% of the hepatocellular carcinoma (HCC) cases seen in Malaysia, and HCC is the third most common type of malignant neoplasm and among the top ten leading causes of death. Following the implementation of the nationwide hepatitis B vaccination in 1989, there was a steady decline of CHB. There is currently no cure to hepatitis B and CHB patients require a daily medication regimen to suppress the hepatitis B viral load. This duration of this regimen is indefinite with the risk of patients developing side effects over the long run. There is an unmet medical need to a CHB cure and this has been the central focus of many pharmaceutical companies. There are several pharmaceutical companies working to develop a cure for CHB. Any of these companies wanting to conduct a trial in Malaysia would know that Prof Dr. Rosmawati Mohamed is a leading key opinion leader in this field.

L-R: Prof Dr Rosmawati awarded the “Top recruiter In Asia – Phase 1b: Session XI” and Dr Syed Mukhtar awarded with certificate of appreciation in ensuring study quality.

While managing the Phase 1b trial (namely HPB1001) clinical study in Malaysia, I had the privilege of working with a renowned hepatologist from the University Malaya Medical Centre (UMMC), Prof. Rosmawati Mohamed. The novel compound may or may not confer therapeutic benefits to the patient, however, the eagerness to look for a functional cure and to improve CHB patients’ quality of life for Prof Rosmawati prevailed. Prof Rosmawati as the principal investigator (PI) headed a team comprising Dr. Roma Basu and Dr. Abdul Malik (sub-investigators), in addition to Dr. Syed Mukhtar and Dr. Zainab Abu Kassim (study coordinators). During this time, Prof. Rosmawati and her team dedicated valuable time and effort in screening for suitable patients. Patients needed to be diagnosed with CHB, but also had to be relatively well in terms of medical health. Furthermore, patients needed adhere to protocol procedures and restrictions while being compliant to prohibited and allowed concomitant medications. At the end of the recruitment period, Prof Rosmawati and her team managed to recruit five patients into the HPB1001 study, ranking Malaysia as the second-best recruiter globally, and ahead of a few countries known for well-established Phase 1 experiences. This achievement puts Malaysia in the limelight as a rising competitive country in conducting Phase 1b trials, despite being initially considered naïve country in Phase 1 studies.

Clinical trials are unable to commence without the approval from a local ethics committee (EC). Moreover, clinical trial proposals submitted to the EC may sometimes warrant justification from the PI on the risk-benefit assessment for conducting such a clinical trial (termed a EC defense meeting). The HPB2001 trial was one of the proposals requiring further clarification, for which Prof. Rosmawati defended excellently. Her effort in defending the proposal during the meeting ensured that the study was approved by the EC on time, allowing for country and global milestones to be met.

Another important aspect of clinical trials is the generation of quality data. Data is collected each time the patient makes a visit to the hospital. This data is compiled and analyzed on a global level, allowing further adjustments to protocols as required. This data is eventually required for the submission to the health authorities for drug approval and marketing. For the HPB2001 trial, Pros. Rosmawati showed great perseverance in ensuring the timely entry of patient data as well as implementing effective retention strategies for the patient during the three-month study period. Prof. Rosmawati managed to retain all of her enrolled patients in the HPB2001 clinical study, symbolizing a mark of excellence.

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In this highly regulated industry, subject safety, data integrity and quality are of the utmost importance. In August 2018, the Malaysia Health Authorities, the National Pharmaceutical Regulatory Agency (NPRA) conducted a three-day inspection for the HPB1001 at UMMC. The outcome was favorable with no major findings or observations noted. The results of this inspection are not only a reflection of Prof. Rosmawati’s dedication to conducting the HPB2001 trial but is also a form of favorable validation on the quality of the research. Furthermore, the success of the inspection is also attributed to the Clinical Investigation Centre (CIC), a clinical department at UMMC dedicated to conducting clinical trials.

Clinical research is a necessary step in sourcing alternative treatment options to many diseases. CHB is one of these diseases. The success of clinical research is largely dependent on the clinical study team chosen to manage it. However, aside from the study team, an even more pivotal element in ensuring the success of clinical trials are the patients. Patients who join the trials allow the generation of data, which in turns leads to more data contributing to the approval of the drug and eventually its availability to the community, hence bringing more benefit to more patients. The willingness of patients who volunteer in the early drug development phase is deserving of commending respect, despite the limited safety and efficacy data generated from pre-clinical studies. Their commitment to clinical trials is regarded as a major contribution in accelerating the development and approval of experimental treatment options. The “I AM AWARE” campaign, designed to increase awareness of clinical research in Malaysia is currently underway. These campaigns conduct regular roadshows at government hospitals and also happen to be a good source of information pertaining to clinical research.


Reference:
Raihan R. Hepatitis in Malaysia: Past, Present, and Future. Euroasian J Hepato-Gastroenterol 2016;6(1):52-55

DISCOVER: DISCOVERing Treatment Reality of Type 2 Diabetes in Real World Settings

According to the DiabCare 2013, despite the effort in improving diabetes care in Malaysia, glycemic control and the prevalence of many diabetes related complications were unchanged over the years.There is still an inertia in getting the patients to clinical targets early with the right treatment.  In view that global real-world data on the management of type 2 diabetes (T2D) are limited, the global DISCOVER study was initiated with the primary objective of describing disease management patterns and disease evolution over 3 years in patients with type 2 diabetes initiating a second-line glucose-lowering therapy.2

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Evolution of Clinical Trial Agreement Review in Malaysia Through CRM

To regulate the conduct, relationships, responsibilities, and obligations of the parties involved in the clinical trial, the Clinical Trial Agreement (CTA) must be in place. The parties in a CTA are not usually limited to sponsors or contract research organizations (CROs), but also include institutions and principal investigators. The Malaysian Guideline for Good Clinical Practice, has defined the CTA as“A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract.”(1)

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Have I Done Enough? – Recruitment and Retention

Read more contents from CRM Bulletin Issue 14. Download here!

The success or failure of a trial strongly lies in the recruitment achievements.  Although clinical trials has been conducted in more than few decades, the recruitment continues to be an immerse challenge for most trials. Investigators enthusiasm for ambitious recruitment targets is often misguided. This is called as “Lasagna Law” where by, investigators overestimate the pool of available patients and at the end of the study fails to deliver the promised target.

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Unraveling the Methodology of Risk Based Monitoring

Read more contents from CRM Bulletin Issue 14. Download here!

The growth of clinical research is extraordinary and the number of clinical trials being approved to run is increasing rapidly in the world. Therefore, there is an increase in the complexity of newer trials as well as the cost of monitoring them. This increasing complexity leads to clinical sites generating more errors during data collection, thus causing delays in the data-cleaning process. Furthermore, there is a higher chance for deviations to occur and be unnoticed at a clinical site. These deviations may directly affect patient safety and data integrity, and is in violation of Good Clinical Practice (GCP). Considering this development, most pharmaceutical companies (or sponsors) are moving towards a new monitoring approach called the Risk-Based Monitoring (RBM) model. For RBM to be defined, a comparative analysis needs to be made between RBM and the traditional monitoring model.

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Site Selection – What a Sponsor Looks For?

Read more contents from CRM Bulletin Issue 14. Download here!

Clinical research is a process that studies a new treatment effectiveness. While it is a very good opportunity for doctors to study the disease development and treatment, the conduct of clinical research by doctors themselves requires a huge budget. Industry Sponsored Research (ISR) provides a good opportunity for doctors to be involved in new and ground-breaking research that may potentially change the course of treatment globally. The number of clinical research has been increasing over the past 10 years. Almost 50% of all trials registered in clinicaltrial.gov showed that it is conducted in Asia. However, less than 1% of the registered clinical research came to Malaysia. To increase the number of ISR in Malaysia, feasibility process plays an important role.

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Malaysia Spearheads Stem Cell Research

Read more contents from CRM Bulletin Issue 14. Download here!

The Ministry of Health (MOH) Ampang Hospital is embarking on a pioneering stem cell research exploring the use of mesenchymal stem cells (MSCs) in acute graft-versus-host-disease (aGVHD). While this innovative treatment has already been approved in several countries, it has so far only been used as salvage therapy after failing steroids and other immunosuppresants, and rarely employed as a front-line therapy. Steroid refractory aGVHD has a dismal prognosis with mortality in excess of 90% and no viable second-line options.1Working in collaboration with Cytopeutics®, a local company with an impressive track record of basic and clinical trials in stem cell, this Phase I-II double blind randomized clinical trial has been approved by the Medical Research Ethics Committee (MREC) and the National Stem Cell Ethics and Research Sub-committee (NSCERT). More centres are expected to participate in the trial locally and abroad including Singapore and Australia. The success of the treatment will provide a real chance of the patient surviving against the odds as well as put Malaysia on the map in the field of stem cell advances.

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Kuala Lumpur Sports Medicine Centre (KLSMC) On Stem Cells Research And Therapy

Read more contents from CRM Bulletin Issue 13. Download here!

Articular Cartilage Repair and Regeneration

Articular cartilage is the soft tissues that surround the bones in the knee joint enabling smooth movement of the knee. Anyone who has suffered or is suffering from damaged cartilage will know just how painful it can be. This can also seriously impact their quality of life and daily function. Regeneration of damaged cartilage has long been thought impossible due to the nature of its tissues. The conventional way of treating cartilage damage often involves complex surgery and is limited to small areas. Even so, the success rates were variable and inconsistent. Often the treatments result in the formation of scar tissues, which cause the cartilage to breakdown faster than normal healthy cartilage; and eventually lead to revision of surgery, higher medical care cost, and little to no improvement in quality of life.

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