1-3 March 2019, Penang, Malaysia
Positive Malaysian Treatment Access and Advocacy Group (MTAAG+), with partners Treatment Action Group and the Foundation for Innovative New Diagnostics, convened the first advocacy workshop on hepatitis C virus (HCV) diagnostics. The workshop presented the latest developments in HCV treatment and diagnostics and prepared community members to participate and raise advocacy concerns at the 4th National Hepatitis Conference (held later on 7-8 March in Kuala Lumpur). A total of 41 participants attended, including family medicine providers and other specialists, technical resource people, and community leaders working with or representing people living with HIV and/or HCV (PLHIV and/or PLHCV), people who use drugs, men who have sex with men, transgender people, incarcerated people, and sex workers.
- Strengthen treatment, harm reduction, and other healthcare advocates’ capacity and technical knowledge on HCV diagnostics
- Foster advocates’ leadership skills and prepare their meaningful community engagement in high-level national decision-making processes associated with timely regulatory approval, guidance development, and scale up of diagnostic technologies.
In addition, the workshop aimed for participants to exchange experiences from different districts and clinical settings, while ensuring the presence of medical expertise and breaking down the silos between medical professionals, advocates, and community members in order to build a coalescent yet diverse and active coalition.
Several strategies and themes emerged to scale up diagnoses, based on the Status Report on Availability and Accessibility of Hepatitis C Diagnosis in Malaysia:
- Increase awareness among people at risk (key populations) to encourage them to go for testing
- Increase decentralization of HCV health services outside hospital settings
- Improve surveillance and collect more comprehensive HCV-specific data
- Strengthen and escalate advocacy for treatment availability
To take concrete steps to address these strategies, advocates developed action plans and a comprehensive list of recommendations, which were presented to Malaysian health authorities in a civil society dialogue at the National Hepatitis Conference. Overall, the key outcomes of the workshop were a clearer overview of the hepatitis C situation in Malaysia and basic understanding of challenges related to HCV diagnostics and treatment among advocates. Furthermore, there was a renewed sense of solidarity and confidence in being advocates on hepatitis C, with a focus to ensure that there will always be civil society representation and input moving forward in national elimination planning.
Download the report below.
Status paper on availability & accessibility of diagnosis and follow up with MoH to remediate to the issues highlighted in the paper.
Availability and accessibility of Hepatitis C diagnosis in Malaysia
The Malaysian Government, particularly the Ministry of Health, has shown a strong commitment to hepatitis C (HCV), in particular, with the availability of effective, all oral direct-acting antiviral (DAA) hepatitis C treatment earlier this year. It is estimated that 380,000 Malaysians are living with Hepatitis C, yet a minority or only less than 10 % have been detected. Therefore, a key factor still outstanding is to find the missing thousands of individuals in Malaysia who are currently infected with hepatitis C but not diagnosed. Early detection of those infected is crucial as successful HCV therapy improves liver disease, reduces the risk of death and liver cancer.
The Foundation for Innovative New Diagnostics (FIND) and the Drugs for Neglected Diseases initiative (DNDi) had recently announced their collaboration with the Ministry of Health (MOH), Malaysia to scale up of hepatitis C (HCV) diagnosis and treatment. The initial diagnostic step that will be taken is decentralized HCV screening at MOH health clinics using pre-qualified rapid diagnostic tests: HCV positive cases will subsequently undergo HCV confirmation to enable them to be linked to HCV treatment as part of a DNDi clinical trial or in government hospitals (https://www.dndi.org/2018/media-centre/press-releases/find-dndi-malaysianmoh-efforts-hepatitisc-screening-treatment/).
The objective of this report is to
- assess availability and accessibility of HCV diagnostic tools in Malaysia
- identify strategies to improve access to HCV testing and improve linkage to care and therefore, support, strengthen and complement Ministry of Health’s existing efforts to scale up of HCV diagnosis and treatment
Figure 1 shows the HCV Care Cascade, not only focusing on the major gap in those diagnosed and aware, but also the possible gaps all along after HCV diagnosis.
The initial step for HCV diagnosis in all hospitals and health centres where mandatory or opportunistic HCV screening done is testing for the presence of Hepatitis C antibodies using laboratory-based assay. Rapid diagnostic test (RDT) for HCV is currently mainly performed by non-governmental organisations such as Positive Malaysian Treatment Access & Advocacy Group and Hepatitis Free Malaysia/Hepatitis Free Pahang.
As the presence of Hepatitis C antibodies implies either current or past or infection, a confirmation step is crucial as only those with HCV viraemia will be considered for HCV treatment. Confirmation of HCV viraemia can be done using either HCV RNA test or HCV Core Ag as recommended by all major international guidelines on HCV management.
In public hospital setting, HCV confirmatory tests can only be done in very few MOH hospitals in Malaysia (Hospital Kuala Lumpur, Hospital Sungai Buloh, Hospital Selayang, Hospital Sultanah Bahiyah, Hospital Umum Sarawak and Hospital Melaka), University Malaya Medical Centre (UMMC) and University Kebangsaan Malaysia Medical Centre (UKMMC). Currently, HCV confirmatory tests are not yet accessible to primary care physicians.
Until recently, HCV RNA testing is limited to HCV RNA quantitative test, which costs at least three times higher compared to the HCV RNA qualitative test. WHO and EASL guidelines recommended using either quantitative or quantitative HCV RNA tests as both tests are equally sensitive assays with a lower limit of detection of ≤15 IU/ml.
In the public hospital setting, HCV RNA qualitative testing was only available in UMMC until recently, where its now available at Hospital Kuala Lumpur and Hospital Umum Sarawak. The test is also available in the Institute for Medical Research (IMR).
In hospitals where HIV RNA tests is done, testing for HCV RNA can also be made available on the same platform in Hospital Pulau Pinang and Hospital Raja Perempuan Zainab II, Kota Bharu.
Although HCV core antigen assays is slightly less sensitive than HCV RNA, a WHO commissioned systematic review which included 44 studies, has provided a high level of evidence that HCV core antigen is good alternative to HCV RNA detection and is strongly recommended both by WHO and EASL guidelines for HCV confirmation. Awareness of HCV core antigen as a confirmatory test for HCV is still lacking, although there is increasing access to this test in 7 MOH hospitals (Hospital Kuala Lumpur, Hospital Ampang, Hospital Selayang, Hospital Sultanah Bahiyah, Hospital Raja Perempuan Zainab, Hospital Sultanah Aminah and Hospital Queen Elizabeth)
Liver disease assessment
The main reason to assess the stage of liver disease is not to miss cirrhosis. Fibroscan is a reliable non-invasive test, but its only available in UMMC and 3 MOH hospitals (Hospital Selayang, Hospital Sultanah Bahiyah, Hospital Raja Perempuan Zainab). Serum biomarkers of fibrosis such as APRI and FIB-4 can be used and have been shown to have a good negative predictive value to rule out cirrhosis.
There is no role for HCV genotyping in the 2018 WHO guidelines as only pangenotypic regimens are recommended. However, as Genotype 3 is the in predominant HCV genotype in Malaysia, accounting for 63% of all HCV in Malaysia, HCV genotyping is still required for cirrhotic patients as the duration of treatment and the need for ribavirin differ according to genotype and treatment experience for certain pangenotypic regimen (eg Daclatasvir/Sofosbuvir)
In the public hospital setting, HCV genotyping is only available in UMMC and Hospital Kuala Lumpur. The test is also available in Institute for Medical Research (IMR).
Assessment of cure and monitoring
HCV RNA test is only required once if used for HCV confirmation and 12 weeks post treatment to assess cure/SVR. For those with cirrhosis, surveillance for HCC is required for life with US +/- AFP measurement, and these are only done at tertiary centres.
If available, HCV RNA quantitative test should be used to assess cure/SVR to save costs.
Strategies to improve access to HCV testing and improve linkage to care
Lack of access to HCV Diagnostic is undoubtedly a major barrier in the HCV care continuum. As recently highlighted, this is fuelled by quasi-monopolies on HCV diagnostics, and the lack of competition has kept prices of reagents at a high price
- Increase public awareness to identify those at risk of HCV
Engagement with family medicine specialists to facilitate identification of those at high risk for HCV had started since 2014 which have been shown to result in an increase detection and notification of new HCV cases in 2016. These should be strengthened further with the use of rapid diagnostic tests (RDT) for HCV screening of those at high risk of HCV.
In addition, the quest to “Find the Missing Thousands” living with hepatitis C who have not been detected should involve many stakeholders, including NGOs and those living with hepatitis C, to make testing more accessible and remove barriers for testing amongst them. There is a need to increase public awareness programmes to identify those at risk of HCV and the use of rapid diagnostic tests for HCV screening is recommended in these settings
- Decentralizing HCV confirmation tests and liver disease assessment
For those tested HCV positive with the initial HCV screening/RDT, reflex HCV confirmatory tests is recommended at the same sitting so these patients are not lost to follow-up.
Nearly 60% of HCV in Malaysia were transmitted amongst people who use drug (PWUD). Mandatory HCV screenings have been conducted in patients with opioid use disorder who are being followed at primary care facilities and medication-assisted treatment (MAT) clinics, with approximately 64% of the 3000 registered patient at government MAT setting annually with slightly higher number of cumulative registered patients at private MAT clinics who are HCV-infected. HCV testing in these settings is limited to anti-HCV test, therefore a large proportion of patients who were tested positive for HCV antibody have not undergone confirmatory HCV testing and liver disease assessment, so these tests should be prioritized at primary care facilities and (MAT) clinics
- Providing simple HCV diagnostic and treatment algorithm
The recently updated WHO guidelines provides a simple algorithm for HCV diagnosis, treatment and monitoring, which can definitely increase the understanding on the steps needed to achieve HCV cure and monitoring thereafter.
- Increase access to DAAs and increase treatment sites
Access to generic DAA is only available at 22 MOH hospitals. To reach the goal of HCV elimination by 2030, the government needs to expand HCV diagnosis and treatment services. To achieve this will require moving beyond hospital settings and necessitate the greater involvement of a broad range of health professionals, especially primary-care providers.
- Efficient procurement and supply management of diagnostics (and DAAs)
Centralised or bulk procurement system or negotiation of cost of HCV diagnostics and DAAs at a national level can translate to more efficiency and lower cost of procurement of reagent and drugs for the government.
The use of using open diagnostic platforms for HCV platforms has been suggested as the way forward to introduce competition and can potentially be very efficient and decrease prices of reagents in the near future. In addition, a nationwide access to generic DAA therapy is urgently needed so that the burden of HCV diagnosis and care management is shared by both the public (including university hospitals) and private sectors.
- McDonald SA, Azzeri A, Shabaruddin FH, Dahlui M, Tan SS, Kamarulzaman A, Mohamed R. Projections of the Healthcare Costs and Disease Burden due to Hepatitis C Infection under Different Treatment Policies in Malaysia, 2018–2040. Appl Health Econ Health Policy. 2018 Aug 25. doi: 10.1007/s40258-018-0425-3
- Ho SH, Ng KP, Kaur H, Goh KL. Genotype 3 is the predominant hepatitis C genotype in a multi-ethnic Asian population in Malaysia. Hepatobiliary Pancreat Dis Int. 2015;14(3):281–6. 5
- Freiman JM, Tran TM, Schumacher SG, et al. Hepatitis C Core Antigen Testing for Diagnosis of Hepatitis C Virus Infection: A Systematic Review and Meta-analysis. Ann Intern Med.2016 Sep 6;165(5):345-55. doi: 10.7326/M16-0065
- World Health Organization. Global health sector strategy on viral hepatitis 2016–2021. 2016.
- Fatiha S, et al. Estimated 3-year acquisition cost of direct acting antiviral (DAA) for the treatment of Hepatitis C in Malaysia in 2018 to 2020. APASL 2018 Delhi
- Near-Monopolies On HCV Diagnostics Curb Competition, Keep Prices High, Research Finds
- Ministry of Health Malaysia. Press Statement Minister of Health 20th September 2017 – Implementation of the Rights of Government for Sofosbuvir Tablet to Increase Access for Hepatitis C Treatment in Malaysia. 2017.
- World Health Organization. Guidelines for the screening, care and treatment of persons with chronic hepatitis C infection. 2018.
- AASLD/IDSA. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. September 2017 Retrieved from https://www. hcvguidelines.org/Treatment-Naive. Accessed 4 September 2018.
Number of interviews: 15
The interview was conducted throughout Malaysia from the period of end of July 2018 to early October 2018, covering non-medical personals and doctors from the government clinics and hospitals.
Below are the summary of our interviewees profile.
The non-medical personals answered both questions one and two thus we recorded their presence in both column on question 1 and question 2.
HCV Diagnostic Survey, Malaysia – July 2018 – Summary Report
ACCESS TO DIAGNOSTIC TESTING
Question 1. Please note the availability of the following tests and their prices in the public sector.
Add rows as needed.
|Test (Diagnosis)||Available in public sector?||Length of result||Total price (per test)||Price paid out-of-pocket by patient||Length of result||
Venue of lab & name.
|HCV Rapid Test Kit||X||On the spot|
|HCV antibody (HCV Ab or anti-HCV)||X||Ranges from 1 – 3 days to
1 – 2 weeks
|HCV core antigen||X||Ranges from 2 – 3 days to 1 week or more.||RM80||Nil|
|HCV RNA PCR||X||1 – 8 weeks||RM400||Nil||Sungei Buloh|
|HCV Genotype||X||4 – 8 weeks||HKL / IMR|
|Fibroscan||X||Depends on opportunities as 3 years ago was immediately||Selayang|
Main issues captures from all the interviews are listed below :
- Budget allocation in government hospital.
- Not maximising use of the existing Gene Expert Machine.
- The length of result available is too long.
- HCV RNA PCR, HCV Genotype can not be ordered directly from KK and has to be referred to the hospital specialist.
- Not aware about the existing Gene Expert Machine available.
- Need to refer patients to hospital for confirmation test (HCV RNA PCR).
- Budget constrain especially for HCV RNA PCR is very expensive test.
- Further (HCV RNA PCR) testings are based on criteria (selective criteria such as patients who are planned for treatment, co-infection cases) at cost constraint.
- More budget allocation as some may not be repeated cases.
- Need integration with TB department.
- Government subsidize cost for reagent.
|Usage of Diagnostic||
|Price procured for the machine.
|Cost per reagent /cartridge||Number of test requested
|Number of test was used per day||Number of free testing.||Number of out source testing.|
|HCV Rapid Test Kit||SD Bioline/ Others|
|HCV antibody (HCV Ab or anti-HCV)||Abbott||23 – 40 tests
|HCV core antigen||
|Available at HKL only|
|HCV RNA PCR
(for TB usage)*
|RM34K – RM80K
|RM70 – RM80
|> 50 tests/day||50 tests/day||Malaysia Liver Foundation|
|HCV RNA PCR
|Cobas||RM200 – RM300||10 – 20 tests per week|
|30 tests and mostly available at HKL only|
|Cobas||RM300 – RM400||1 – 5 tests per week (New)|
|RM200K – RM700K||10 cartridges||25 cartridges per week||All free||No.|
* Note: Gene Expert IV – existing 19 units for TB usage in MoH hospitals, and propose 14 units for HIV/HCV usage, and most of them are on reagent rental contract. Prices are based on procurement through reagent rental. This would also depends on workload such as number of tests performed per year basis. Obviously analyser as an asset would offer lower prices.
Most countries will struggle to eliminate hepatitis C by 2030 due to lack of investment and political will, missing an internationally agreed target set by the World Health Organization, The International Liver Congress in Vienna heard earlier this month.
“Despite the progress we’ve seen, we’re clearly not going to make it,” said Gottfried Hirnschall, Director of HIV and Hepatitis at the World Health Organization (WHO), speaking at a symposium on elimination of viral hepatitis organised by WHO.
The World Health Assembly agreed ambitious targets for elimination of viral hepatitis in 2016. Countries pledged to scale up prevention, diagnosis and treatment so that deaths caused by viral hepatitis would be cut by 65% and new infections cut by 90%
Although 124 countries now have national plans for viral hepatitis elimination, 42% of plans have no domestic funding, Mark Bulterys, head of WHO’s hepatitis team told the symposium.
Furthermore, although 5 million people had been treated with direct-acting antivirals (DAAs) by the end of 2017, most of these treatments occurred in ten ‘champion countries’ which have scaled up treatment quickly, including Egypt, Brazil and Australia.
Even in higher-income countries, hepatitis C elimination may only be achieved by a handful of countries by 2030, the Center for Disease Analysis estimates. Nine countries – Australia, France, Iceland, Italy, Japan, South Korea, Spain, Switzerland and the United Kingdom – will achieve elimination by 2030 at current rates of diagnosis and treatment.
Elimination may not occur before 2050 in Canada, the United States and smaller European countries, the modelling exercise found. Two-thirds of higher-income countries are seriously off-track, the Center for Disease Analysis reported.
Despite dramatic reductions in the prices of generic versions of DAAs to less than $100 per cure, some lower-income countries are still paying substantially higher prices although they are eligible for low-price drugs under voluntary licensing agreements. Sixty-two per cent of people with hepatitis C live in countries covered by these agreements, which allow generic versions of DAAs manufactured under voluntary licence from the originator company to be imported from countries such as India or Egypt.
WHO has calculated how much it will cost to eliminate hepatitis C by 2030. Its model, developed by Dr Melikha Toy of Stanford University, estimates that it will cost $58.8 billion to achieve elimination of viral hepatitis by 2030, slightly higher than the estimate presented by Professor Margaret Hellard of the Burnet Institute, Melbourne, on the opening day of the conference.
But Dr Toy said that the cost of elimination could be considerably lower if drug prices fall rapidly, if countries use voluntary licensing arrangements to obtain low-cost drugs, and if the cost of diagnostics falls, especially hepatitis B DNA testing. A large part of the cost of elimination will be the cost of HBV DNA monitoring, and much of the cost of elimination will be concentrated in the Western Pacific region and Africa due to the high burden of hepatitis B in those regions, she said.
The cost of elimination would add 1.5% to the total budget for universal health coverage proposed by WHO in 2017. The budget set out how much it would cost to achieve the Sustainable Development Goals for health by 2030 through universal health coverage in 67 lower- and middle-income countries. Hepatitis diagnosis and treatment was not included in that costing.
“If you look at data, and ask, ‘what is hepatitis achieving in the context of universal health coverage’, it’s just about getting off the ground,” Dr Gottfried Hirnschall told infohep in an interview.
“We hear about Egypt, Mongolia, Georgia, China, Brazil, but there are many other countries that are not moving yet. There are whole continents that are falling behind, Africa when it comes to hepatitis B, and for hepatitis C some of the larger high burden countries are not moving sufficiently – Russia for example, and China still has a long way to go despite some positive momentum that has been building up.”
“A movement has been created, the momentum has been sparked, the feasibility has been demonstrated in some countries but too many others are still looking across the fence and finding easy excuses for not doing it.”
To maintain a positive trajectory and accelerate it, advocacy will still be needed. We must not give the impression that HIV is almost done, and we must encourage countries to factor those services into a broader health financing approach, and we see that in some countries, such as Thailand.
“In hepatitis, we have to demystify that management is highly complex and can only be done by hepatologists – we are here at a hepatology conference and we need to convince them, ‘it’s not just your job, it can be done by any general practitioner’ and in some low-income settings it could be simplified further, which is what we’ve seen in HIV.”
Read more at : http://www.infohep.org/page/3478324/?utm_source=NAM-Email-Promotion&utm_medium=conference-bulletin&utm_campaign=English&fbclid=IwAR3cidqV0T8sSNjm2w_TeW9IA904gmGI5DJopHfsobf1xqogHcrQOxJEFsQ
1 May 2019, PORTO – The World Health Organization (WHO) is calling for greater commitments to scale up hepatitis C virus (HCV) testing and treatment services to people who inject drugs (PWID) and people in prisons (PIP).
Around 71 million people are infected with chronic HCV worldwide with PWID being disproportionately affected. They account for the highest proportion of new infections – 23% of the 1.75 million infections that occur every year. As for PIP, up to 1 in 4 can be HCV positive. The elimination targets set by WHO aim to diagnose 90% and treat 80% of all eligible persons by 2030.
Today at the Harm Reduction International Conference (HR19), WHO is releasing a new policy brief “Access to hepatitis C testing and treatment for PWID and people in prisons – a global perspective”. The policy brief looks at the global landscape of national hepatitis plans and country experiences, showcasing some of the gains and gaps in reaching PWID and PIP with HCV services.
The policy brief outlines the following analysis.
- More countries have developed national hepatitis plans as at February 2019, but many of these plans overlooked the needs of PWID and PIP.
- Of the 81 national plans and treatment guidelines reviewed by April 2019, 51 (63%) included services for PWID, and 37 (46%) did so in full alignment with the WHO “Global health sector strategy on viral hepatitis, 2016–2021”.
- 28 (35%) plans and guidelines included services for PIP, and 23 (28%) did so in full alignment with the WHO “Global health sector strategy on viral hepatitis, 2016–2021”.
- 11 (14%) plans and guidelines specified restrictive requirements such as drug use abstinence (commonly for a period of 6 months or longer) for PWID to be eligible for HCV testing and treatment.
- Many national plans and guidelines also specify requirements for health insurance coverage, which presents a barrier for PWID and PIP in some countries.
The policy brief also provides select country experiences:
- Australia recently published its fifth national strategy (2018–2022) on the path to hepatitis elimination by 2030. The country used a simplified approach to service delivery, integrating hepatitis testing, treatment and harm reduction for PWID at decentralized sites, and engaging peer workers and general doctors. Concerted implementation of HCV testing and treatment in several prisons shows elimination in these settings is possible.
- China is undertaking development of a national hepatitis plan, which references PWID as a priority population for HCV testing and treatment. The government and health insurance providers are in the process of negotiating lower prices for DAAs – the results of these negotiations will be key to the strategy’s success.
- India launched a national action plan to combat viral hepatitis in February 2019, targeting PWID as a priority population, aiming to provide 1 000 000 DAA treatment courses annually over the next 3 years.
- The Islamic Republic of Iran has a 3-year national hepatitis plan that proposes interventions for PWID and PIP. DAAs can be obtained for as little as US $81, but only for people with health insurance. Many PWID and PIP without insurance face a higher cost of US$ 2200.
- Ukraine is developing a national strategy to contain tuberculosis, HIV and viral hepatitis. Generic DAAs are now available for less than US$ 100. Effective collaboration with the Ministry of Justice enabled HCV testing for 1 000 PIP living with HIV in 2018. Of these people, 50 were treated with DAAs, achieving a 98% completion rate.
- The United States of America also has a viral hepatitis action plan and policies that target PWID and PIP. But high costs for DAAs (between US$ 15 000 and US$ 94 000) are a major implementation barrier.
Steps for HCV elimination among PWID and PIP
The WHO policy brief calls for greater political will to improve testing and treatment access for these marginalized populations. HCV treatment prices also need to drop further. Reaching PIP with public health services is feasible– and can help achieving HCV elimination within this specific population group.
Reaching PWID and PIP with HCV testing and treatment services as part of a comprehensive harm reduction approach is an essential element of hepatitis elimination efforts and embodies the principles of the Universal Health Coverage (UHC) agenda to ensure that no one is left behind.
Reflecting voices of PWID and PIP and other key and at-risk populations in shaping hepatitis elimination and UHC efforts is a critical step as well. This week, WHO is supporting the participation of 7 key population scholars in multi-stakeholder consultations, in preparation for the UN High-Level Meeting on UHC to take place in September 2019.
Salam #Ramadan dan Selamat Berpuasa. Nama saya Basri, saya bertugas sebagai rakan sokong bantu bagi program TAPS (Treatment and Adherence Peer Support) bersama NGO Persatuan Perantaraan Pesakit Kelantan. Saya juga seorang PLHCV (people living with #hepatitis C), saya telah ketahui status saya sejak tahun 2007. Saya mengetahui mengenai rawatan baru DAA #HCV apabila mengikuti workshop bersama MTAAG+. Saya mengalakkan komuniti PWID/PWUD (people who inject drugs/people who use drugs) di Kelantan untuk menjalani saringan dan mendapatkan rawatan HCV yang percuma di fasiliti kesihatan kerajaan. #akujanjiubatiHepC
To end viral hepatitis by 2030, communities are key. We have effective treatments and harm reduction measures, but less than 5% of 71 million people living with hepatitis C have been treated.
“For the community, by the community, with the community”
Join us in our fight: www.coalitionplus.org
UNITAID Malaysian AIDS Council KEMENTERIAN KESIHATAN MALAYSIACoalition PLUS
Gram for gram a HIV medicine costs more than gold.
What makes drugs so costly?
Is it research and development, or have the prices of essential, life-saving drugs been ramped up by a lack of transparency and abuse of a system intended to reward innovation?
Estimated read: 7 minutes
26 April 2019 is World Intellectual Property Day. Intellectual Property. IP. Must be important, to have its own day? So, what do you know about it?
It’s something to do with rights, right? Along the lines of if you invent something, something that you’ve invested time, money and more than a sprinkling of ‘genius’ in, then you can patent your invention for 20 years. That ensures that someone else can’t just come along, copy your idea and make a quick million bucks off the back of your hard work. Sounds fair enough?
A lot of people think of an inventor in a shed, or state-of-the-art tech when you say ‘IP’. But what about when it’s medicines being patented? You can choose whether or not to buy a swanky new gadget, but you don’t choose to get sick, and you don’t choose to need a medicine that gram for gram costs more than gold.
That’s why some people think medicines shouldn’t be owed by anyone, that they are for the good of the people and shouldn’t be monetised at all. Like Jonas Salk, inventor of the polio vaccine, who when asked ‘who owns the patent?’, famously said: “The people, I would say. There is no patent. Could you patent the sun?”
On the other hand, many would argue, discovering new medicines takes time. Lots of it, decades of development and testing, depending on which accounts you read. Plus, after rigorous testing for efficacy and safety, the majority of drugs don’t make it to market (unless you lie about it of course), and who’s supposed to foot the bill for that?
If (and we’ll come back to this word shortly) companies, rather than governments, invest all this time and skill, then there’s got to be an incentive, right? After all, pharmaceutical companies aren’t in it simply for the good of their health, they are a profit-making industry and don’t feign otherwise.
The flow of invest-reward-invest-reward is supposedly what keeps the cogs turning; new medicines being invented; sick people made better.
Then why do pharmaceutical companies seem to get so much flack these days? After all, it sounds like they are just protecting their hard work. Why do treatment activists and pharmaceutical companies who, on the face of it, should be on the same side, have such a bad reaction towards each other? Let’s examine the hotly contested research and development (R&D) argument.
‘Monopolies are necessary in order to recoup the investment and put more money into developing new drugs.’ This, or phrases along these lines, are Big Pharma’s favourite tropes. The industry has repeated this for years. But is it true?
Let’s break it down. To assess the argument’s merit we need to discover who invests in R&D, whether the amount being recouped is fair, and whether that actually leads to more innovation.
R&D: It’s NOT a solo venture
Billions go into biomedical research and development every year. Each year it fluctuates from country to country, and it is generally a combination of public money and industry investment.
The current trend is for the majority of investment to come from industry. It’s to be expected, as the whole point of the present system is for those that invest to get a return. No-one’s begrudging a fair profit, after all that was the idea: invest-reward-invest-reward.
The pharmaceutical industry is the third most profitable in the world, so there are pretty healthy returns, and it’s a strong indicator that profits have gone way beyond a point of merely recouping costs.
The pharmaceutical industry is the third most profitable in the world.
Add to that that not all investment comes from industry, it varies from country to country, but a decent percentage comes from government. Take the USA as an example, in 2017 67% of medical investment came from industry, but 22%, not an insignificant proportion, was funded by the government.
Presumably that would mean that around 1 in 4 medical patents in the USA are owned by the government, and can be priced fairly for the good of citizens, based on the proportion of investment. They don’t. So where is that return on the government’s investment going?
Who’s paying for patents?
Only last month, a Washington Post headline ran: An HIV treatment cost taxpayers millions. The government patented it. But a pharma giant is making billions.
The drug is Truvada for PrEP, the company is Gilead.
The New York Times also ran a piece on the same example. In it the columnists, co-founders of PrEP4All, explain how the price for generic Truvada costs less than $6 per month in other countries, “but Gilead charges Americans, on average, more than $1,600, a markup from the generic of 25,000 percent.”
It continues: “Infuriatingly, American taxpayers and private charities — not Gilead — paid for almost all of the clinical research used to develop Truvada as PrEP.”
This is not uncommon. Often drugs initially developed in the public sector are bought, not invented, by pharma companies, which then complete the development and file the patent.
In this case surely the argument, that such high prices are necessary to recoup costs from years of investment, has to be thrown out of the window.
Gilead has earned $36.2 billion on Truvada since 2004 according to its annual reports. The total funding needed to get the HIV response back on track has been estimated at $26 billion annually.
Why is the USA government paying for a drug that it largely funded, and allowing an unfair profit to be made by a private company when there’s a shortfall in HIV funding?
Treatment activists have been wondering whether it’s the “cosy relationship” between government and Gilead that prevents the government taking a stand on a patent that by rights shouldn’t belong to a pharmaceutical company.
Not only is the pharmaceutical industry is the world’s third most profitable industry, it’s also THE largest lobbying power in the USA.
Why is the USA government paying for a drug that it largely funded when there’s a shortfall in HIV funding? And why the need for such heavyweight lobbying?
Say Truvada for PrEP was the exception and not the norm. If the system was fair and therefore it was patently obvious that countries must pay for the price of investment, then why the need for such heavyweight lobbying?
Industry’s influence on, or in, government
As THE largest lobbying power in the USA, pharmaceutical companies effectively have a seat at the government’s table, and not just figuratively speaking.
Pharmaceutical companies have a seat at the USA Government’s table, and not just figuratively.
Alex Azar is a lawyer, pharmaceutical lobbyist and former drug company executive. He’s also the current Secretary of Health and Human Services. Let’s repeat that. A pharmaceutical lobbyist holds the USA’s most senior health role.
In ‘NO is not enough’ Naomi Klein describes what’s happening in Washington since Trump’s election as a “naked corporate takeover”. Klein writes: “Apparently, all that wining and dining of elected officials, all that cajoling and legalised bribery, insulted their sense of divine entitlement. So now they’re cutting out the middlemen – those needy politicians who are supposed to protect the public interest – and doing what top dogs do when they want something done right: they are doing it for themselves.”
Who else who sits on Trump’s cabinet? Sitting alongside Azar is a millionaire investor who lied about his net worth. He’s the Secretary of Commerce. An investment banker and previous hedge fund manager is Secretary of the Treasury. Exxon-Mobile, General Dynamics, Boeing, and Goldman Sachs alumni and board members have also sat round the table in Washington in official roles. This shows that Azar is not the only one holding a position with a glaring conflict of interest. “Trump’s cabinet of billionaires and multimillionaires tells us a great deal about the administration’s underlying goals,” writes Klein.
When you think of it it beggars belief, you couldn’t make it up, and yet it’s true. How about numbers though, can you make those up?
How much does drug development cost?
Unfortunately the one thing numbers can’t add up to is agreement.
Estimates for the cost of a medicine, “from invention to pharmacy shelves” varies from $30.3 million to $2.7 billion. This guys argues, in Forbes, that it’s the upper limit. In his words: “What really drives up costs is the fact that 90% of medicines that start being tested in people don’t reach the market because they are unsafe or ineffective. The $2.7 billion figure includes the cost not only of these failures, but also of not putting the money spent on them into something that would give a more reliable return.”
The high-end figures come from industry-funded studies, and as an MSF report states, they chose to include “arbitrarily inflated” costs yet don’t account for the public support.
Big Pharma is notoriously un-transparent about R&D costs. While that remains the case we’ll never know the true costs, but even if you take the low end of the calculations it begs the question, ‘how much profit is enough?’.
How much profit is enough? Blockbuster Drugs
Take a ‘Blockbuster Drug’, two words that, for many, sit together uncomfortably. The pharmaceutical industry defines a blockbuster drug as one that meets the “$1 billion USD annualsales milestone”.
Let’s do a quick calculation: $1 billion per year (minimum) x 20 years standard monopoly = $20 billion (minimum).
That was easy. However, it might take a blockbuster drug up to four years to reach its potential. Let’s knock off $4 billion – of course they don’t earn nothing in the first four years, but just for ease, plus let’s also minus the top-level, industry-funded estimate ($2.7 billion) that a company invested.
That’s now ‘dwindled’ down to $13.3 billion. Of course, not every drug is grossing $13 billion plus, but we also know not every, if any, drug costs $2.7 billion to create either. To provide some context, Avatar is the most expensive movie ever made. The costs were over $478 million and it grossed over $3 billion worldwide. At least $10billion less than a blockbuster drug.
The most expensive movie ever made grossed $10 billion less than a ‘Blockbuster Drug’.
A less dramatic way to look at it would be to take each drug on the World Health Organization’s (WHO) list of essential medicines and compare the cost and price of all the drugs on it. That’s what researchers at the University of Liverpool did. The research looked at cost of production, which included manufacturing, formulation, packaging, taxation and a 10% profit margin. It found a significant gap between the cost and price of the majority of medicines on the list.
Still though: Innovation, innovation, innovation
So prices for patented medicines are excessive. However, perhaps even for those uncomfortable with such steep profits being attached to medicines, maybe the incentive of earning billions is OK if it achieves an end goal of discovering more effective drugs, and more breakthroughs and cures?
After all, once the 20 year patent period has expired we should expect that competition gets introduced, prices drop massively, and pharma companies race to find new, effective (and profitable) drugs.
But wait. A patent doesn’t always end after 20 years. There’s a common practice called evergreening. This is when companies effectively extend their monopolies by applying for multiple, overlapping patents, with small changes, on the same drug.
A monopoly often doesn’t end after 20 years.
Take Thailand. During an 11 year period (1999-2010) 82% of patent applications were examples of evergreening, and 72% of patents granted also fell into that category. In one example there were six patents and a total monopoly period of 31 years on one drug.
Even in cases of genuine innovation, it means nothing if you, or your government, can’t afford the drug that’s needed to save your life. 15.2 million of the 36.9 million people living with HIV do not have access to treatment.
Investing in drugs, or patents?
Instead of incentivising innovation, the practice of evergreening patents actually stifles innovation, leading to less medical breakthroughs. If you can continue to make millions or billions on an existing product it removes much of the profit motivation to develop new products.
Paediatric drugs have particularly suffered due to this practice, due to a ‘limited market’. It seems that sick children just aren’t profitable enough.
“We are not markets, we are people” – Lorena Di Giano, Executive Director, Fundación GEP.
A country can refuse to grant an unmerited patent, including evergreening patents, while an application is pending, or, when a patent is granted issue what’s called a compulsory license, which effectively overrides the monopoly if there is a public health need. The classic case for the latter is when a government can’t afford to treat all people in need at the prices charged, and to prevent or tackle a public health crisis, it uses its legitimate right to source more affordable, trusted, generic versions.
This is all laid out in a multilateral agreement know as TRIPS (Trade Related Aspects of Intellectual Property Rights Agreeement) and the Doha Declaration (Declaration on the TRIPS agreement and public health. The problem is that often when governments legitimately push back pharmaceutical companies use their legal and financial muscle to push back harder.
Examples of how that ‘push back’ has manifested in the past include threatening an impact on trade, or refusing to register new drugs in a country. One reason countries may decide not use the ‘flexibilities’ entitled to them under the TRIPS Agreement is the fear of these types of consequences. Another theory as to why these rights aren’t enacted in the first place is because if industry is within governments or at least influencing them, then governments are less likely to act, as they’d effectively be pushing back against their own interests.
The current system, connected to the enigma of R&D costs, keeps prices and profits unfairly high, and there’s little or no recourse. One proposed solution is de-linkage. The argument is that R&D funding should not be tied to the price of the product. Monopolies and high prices would be replaced with alternative incentives based upon cash rewards, and expanded funding for research, drug development, and clinical trials through a combination of grants, contracts, tax credits, and other subsidies.
The R&D argument is unmerited
The current system, and the arguments made by pharma that prop it up, amounts to a lot of profit but not much else.
There are many more examples of IP abuse that can be cited here, and so for an industry built on medicines, there’s an unhealthy amount of controversy.
If you wnat more convincing, consider these salaries: Among the recent top 10 highest paid pharma bosses was the Gilead CEO taking home $13.9 million a year; the AbbVie chief exec securing a $18.8 million salary (that’s the company that pulled all new drugs when a country enacted its rights), and the Bayer boss earning $25.27 million.
That’s per year, just take that in. In just one year, 110,000 children died of HIV-related illnesses. $25 million, ONE person’s salary, could be enough to provide 416,000 children with life-saving HIV treatment for a year. Now that’s got to make you sick.
read more at : http://makemedicinesaffordable.org/en/whats-wrong-with-ip-rights-protecting-medicines-from-competition-can-be-costly/?fbclid=IwAR2HJTweUSAGILrpJFiy73SDq_AXxB2jlmPkIfLtKHp1x13fD85IcR0uRbM
“Medical innovation has little social value if most people cannot access its benefits…. this is a global human rights issue,” said Mariângela Simão, Assistant Director General at the World Health Organization (WHO), at the opening of the second WHO Fair Pricing Forum, co-hosted by South Africa, which took place 11-13 April 2019 in Johannesburg, South Africa.
The Forum brought together over 200 delegates from government, NGOs, academia and industry to discuss how to design a fairer pharmaceutical system where medicines are affordable to those in need and the development of effective new treatments is financed appropriately. Medicines Law & Policy was invited to present the TRIPS Flexibilities Database at the Forum; this database lists instances of the use of provisions in patent law to reduce prices on needed medicines, shedding light on how often they have been needed.
Calls for drug price and cost transparency grew louder at the second Forum, though they began at the first Fair Pricing Forum held in the Netherlands in 2017. High prices are defended by pharmaceutical companies as necessary to recoup costs of research and development (R&D) and incentivise further research, but with little clarity on how much R&D truly costs nor how medicines prices are set it is difficult to objectively determine what price is fair. Cases of exponential increases in the price of previously affordable drugs when market exclusivity was obtained were cited as examples that current prices seem to be more about profit than recouping costs.
Cancer took centre stage
The cost of cancer treatment took centre stage at the Forum, with the WHO’s report on the pricing of cancer medicines providing important background. The study found that the costs of R&D and production may bear little or no relationship to how pharmaceutical companies set prices of cancer medicines. Return on investment is more than generous with an average income of US$ 14.50 for every R&D dollar spent.
Cancer patients from South Africa gave powerful testimony at the Forum (and outside where activists were demonstrating and addressing the media) of the hardship caused by the high cost of the treatments.
One patient, who asked to remain anonymous, described his quest to gain access to the treatments he needs. Three years ago, he was diagnosed with multiple myeloma. His doctor prescribed lenalidomide, a derivative of thalidomide, which is sold under the brand name Revlimid by Celgene. In India, generic lenalidomide is available for R32,000 (US$ 2289) per patient per year. Until 2016, South African patients had access to generic lenalidomide from India under a section 21 authorisation that allows the sale and use of unregistered products. This authorisation was withdrawn once Celgene registered the product in the country. Celgene priced it at R882,000 (US$ 63,000) per patient per year. While the health system provides the drug, patients are struggling to pay the 20% co-payment. South Africa’s GDP per capita is US$ 6,160. According to the Cancer Alliance, South African patents block access to generic lenalidomide and this may last until 2028. Celgene told its shareholders earlier this year that it expects sales of Revlimid to be around US$ 10.8 billion in 2019. Bristol-Myers Squibb is currently in the process of taking over Celgene for US$ 74 billion.
There are similar issues with other cancer medicines. Trastuzumab (Herceptin), a WHO essential medicine for the treatment of HER2 positive breast cancer, costs R130,632 (US$ 9,295) in the public sector and R475,380 (US$ 33,827) in the private sector in South Africa. Biosimilar versions of trastuzumab are beginning to become available elsewhere in the world because the basic patent expired in 2016. But not in South Africa, where the company Roche continues to benefit from a market monopoly. The production cost of this same treatment is around US$ 240 for a one-year supply. Roche’s annual sales for the product is around US$ 7.5 billion.
Pembrolizumab (Keytruda) is a second-line treatment of non-small cell lung cancer and is priced at R180,000 (US$ 43,000). The Forum was told that to treat all in need would cost the South African health system R200 million (US$ 48 million).
These stories helped to set the scene and impress on participants to the Forum that there is no fairness in the system and that finding solutions to the problem of high drug pricing is urgent. Just as it was 20 years ago for HIV.
Pharma vs Nelson Mandela
In the past, South Africa has been the scene of some of the fiercest battles for access to medicines. Director General for Health, Precious Matsoso, recalled some of the histories at the opening ceremony. In 1998, at the height of the HIV crisis, 39 mostly multinational drug companies took the South African government to court over new provisions in its medicines law designed to accelerate access to lower-priced medicines. The companies claimed that the provisions were unconstitutional and in conflict with South Africa’s obligations under the TRIPS Agreement. Three years later, in 2001, the companies dropped the case after a global outcry and after it became clear that the legal text in question was based on draft legislation provided by the World Intellectual Property Organization (WIPO).
By then the case had become widely known as Pharma vs. Nelson Mandela and spurred global action on access to HIV medicines, strengthened flexibilities in patent law and made an industry in need of atonement agree to lower prices and later to offer patent licences to ensure low priced generic HIV medicines could be made available.
Twenty years ago, access to medicines was predominantly a problem for developing countries. “Today access to medicines has become a global issue”, said Simão.
Drug pricing a global issue
In Switzerland, the civil society organisation Public Eye requested the government for a compulsory licenceon the patents related to the breast cancer medicine pertuzumab, sold by Roche under the brand name Perjeta. The US$ 100,000 price tag of Perjeta in Switzerland underscored the point that medicines pricing is a global issue. Similar demands have been made in other countries. Wilbert Bannenberg, chair of the Dutch Pharmaceutical Accountability Foundation described the case of a rare disease medicine, CDCA, used for the treatment of the metabolic illness cerebrotendinous xanthomatosis (CTX). For years, the product was available for € 300 per patient per year and prescribed off-label to treat CTX. After the drug company, Leadiant was granted exclusive rights to market the product in Europe for CTX in 2017, it increased the price to € 153,300 per treatment-year. Bannenberg’s presentation emphasised the need for competition authorities to take action against excessive drug prices. He further outlined his organisation’s plans to use the law (competition law, patent law, human rights law, civil law) to challenge unfair medicines pricing.
It may have been coincidence that shortly after the start of the Fair Pricing Forum, the Dutch Minister of Health Bruno Bruins announced his plans to reduce the exclusivity for orphan drugs from 10 to 5 years in the EUropean Union (EU) and to establish a commission to study the use of compulsory licensing to gain access to lower priced medicines in the Netherlands. A review of the pharmaceutical incentives in the EU is underway. Bruins also decried the lack of transparency in drug pricing and cost of R&D.
Dr Salmah Bahri, director of pharmaceutical services at the Malaysian ministry of health, described her country’s comprehensive approach to selecting and financing access to essential medicines. Malaysia does not shy away from using compulsory licensing when needed and has reduced the cost of hepatitis C treatments from US$ 72,000 to less than US$ 300 in the public sector by allowing generic import and supply of the product. They are also working with the Drugs for Neglected Diseases initiative (DNDi) on the development of a low-cost hepatitis C treatment.
Gaëlle Krikorian, from Médecins Sans Frontières (MSF), told the meeting about vaccine pricing challenges the organization deals with. MSF’s Access Campaign succeeded in persuading Pfizer and GlaxoSmithKline to significantly drop the price of the pneumococcal conjugate vaccine (PCV) for humanitarian organizations. Organisations working in emergency settings can now obtain the vaccine for US$ 9 per child under the ‘humanitarian mechanism’. It took seven years of negotiation to obtain the lower price. While this is good news for children in crisis settings others cannot benefit from this price. The list price of the vaccine is US$ 540 per child. In reality, prices vary but are high: France pays US$ 189, Lebanon US$ 243 and the price in local Greek pharmacies is US$168. MSF recently announced that it will use the “humanitarian mechanism’ to protect refugee children in Greece against pneumonia, the world’s ‘number one childhood killer’ according to MSF. Since 2009, Pfizer and GSK have earned $49.1 billion in sales from the pneumonia vaccine, said MSF.
Othman Mellouk from the International Treatment Preparedness Coalition (ITPC) also drew attention to the plight of people in middle-income countries. He mentioned the case of dolutegravir, an essential medicine for the treatment of HIV which will be available for US$ 75 per patient per year in low and middle-income countries. The patent license agreement reached by the Medicines Patent Pool with ViiV and the price deal brokered by the Clinton Health Access Initiative and partners exclude 39 countries, mostly upper middle-income countries. The World Bank defines lower middle-income economies as those with a GNI per capita between $1,006 and $3,955 and upper middle-income countries as those with a GNI per capita between US$3,956 and US$12,235. Above this figure, the country is considered high-income.
Transparency, transparency, transparency
The call for transparency emerged as the central theme of the meeting, in particular with regard to medicines pricing, production cost and expenditures on R&D. 64 civil society organisations published a statement before the meeting calling for greater medicines pricing and R&D cost transparency.
Andrew Hill presented data on the production cost of essential medicines that demonstrated most of them could be produced for a fraction of their current prices. For example, the price based on production cost for the US$ 30,000 per patient per year cancer drug imatinib can be as low as US$ 180 per patient per year. Insulin, which was discovered in 1923, cost US$ 1 per vial to make but is sold at US$ 240 per vial today. The global insulin market is valued at US$ 28 billion. Greater price transparency will help countries to understand the savings they can make by buying generics. The same call could be heard earlier this year at the Executive Board of the WHO. Since then, Italy has proposed a World Health Assembly resolution to improve the transparency of markets for drugs, vaccines and other health-related technologies. The resolution is expected to be discussed at the 72nd World Health Assembly that takes place from 20 – 28 May 2019.
The need for greater transparency in R&D cost was brought forward by the first Fair Pricing Forum, including the potential it has for designing targeted rewards for needed innovation.
Thomas Cueni, director general of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) fiercely resisted the calls for transparency on medicines pricing. He warned greater transparency on medicine prices could backfire, and drive up drug costs in low and middle-income countries. This could, for example, be the case if high-income countries would refer to low prices available in low-income countries and demand the same lower prices or use it for reference pricing. Meeting participants seemed to agree with making provisions needed to allow for significant differential pricing. However, Suerie Moon from the Graduate Institute in Geneva pointed out that this would require more reasonable pricing in high-income countries as well. A fair price, she explained, is one that covers the cost made by the seller (including R&D, manufacturing and distribution, and fair profit) and assures affordability, value to the individual and the health system and security of supply to the buyers.
Jamie Love, director of Knowledge Ecology International, warned against using patient coverage as leverage in price negotiations. “Put the compulsory licensing of patents on the table, so that the monopoly is at risk, rather than the patient,” he said. He further outlined a proposal to finance the cost of R&D in a different manner. “Temporary monopoly is the primary incentive today, enforced by patents and a variety of regulatory monopolies. This is expensive and the primary reason why prices are high and access unequal,” Love said. By implementing models that de-link the cost of R&D from the price of medical products to finance drug development, high prices are no longer required to recoup R&D expenditures. He mentioned market entry awards and product prizes as two possible such models. He proposed a progressive implementation of de-linkage awards to gradually replace market exclusivities. A next step should be a feasibility study of the proposed new models. Such exploratory work would also benefit from greater transparency.
One successful example of an innovation initiative that works with a delinked model is the Drugs for Neglected Diseases Initiative (DNDi). The DNDi is open about its R&D outlays. “We need to be publicly accountable and be able to show the public’s return on the public investments we use to develop new treatment’ said Michelle Childs, head of policy advocacy at the DNDi.
The Medicines Patent Pool is another example of an organisation committed to transparency. The MPP publishes all its agreements in full on its website. The MPP initially focussed on HIV and later hepatitis C, but has expanded its mandate to negotiate licenses for all patented essential medicines. One company, with a significant cancer portfolio that was present at the Forum indicated that it is in talks with the MPP.
At the closing of the meeting, Fatima Suleman, a professor in pharmaceutical sciences at the University of KwaZulu-Natal and chair of the National Medicines Pricing Committee, noted the striking increase in research, available data and analysis to inform better policy making on medicines pricing and cost. Indeed, telling examples presented at the meeting included the WHO report on cancer drug pricing, the research on production cost of essential medicines by Andrew Hill, analysis on how to determine a fair medicine price and work on transparency by Suerie Moon, the TRIPS Flexibilities Database by Medicines Law & Policy, the patent opposition database, medicines patent analysis by I-Mak, the patent status information databases Medspal by the Medicines Patent Pool and Patinformed maintained by WIPO in collaboration with the IFPMA, and the drug research, development and pricing information database by Knowledge Ecology International.
The WHO announced it would set up working groups to further develop proposals put forward at the meeting before the next Fair Pricing Forum takes place in 2021. WHO will also launch an online public consultation in the coming weeks to collect suggestions for a definition of what constitutes a ‘fair price’. The next milestone will be the discussions on price and R&D cost transparency at the World Health Assembly this May of year.
The presentations made at the meeting will be available at the Fair Pricing Forum website.
Read more at : https://medicineslawandpolicy.org/2019/04/strong-call-for-transparency-on-medicine-prices-cost-of-rd-at-who-fair-pricing-forum/?fbclid=IwAR3yzXxMJ6efmTaCvUvmxXxZpuuTWa2yp7qPvNCfIVvVIFAV5yeJcPnfIbk