Monthly Archives: January 2017

How Cost-Effective Are New Cancer Drugs?

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The main reason why cancer is so serious a disease, is the ability of the malignant cells to spread in the body, both locally by moving into nearby normal tissue, and regionally to nearby lymph nodes, tissues, or organs, affecting even the distant parts of the body. When this happens, doctors term it as metastatic or stage IV (four) cancer.

Although most patients with metastatic tumors would eventually die of cancer, the treatment with various types of anticancer drugs, could help prolong life, in varying degree. No wonder, many new anticancer drugs now obtain regulatory approval based on their effectiveness on metastatic cancer patients. Consequently, it has now become almost a routine to administer newer anticancer drugs to patients with early stage of disease, after they have undergone surgery or radiotherapy.

But, these lifesaving drugs are expensive – very expensive! For example, a newer anticancer treatment is often priced at US$ 100,000 or more per patient, which, obviously, a large majority of the population can’t just afford.

Are these new drugs cost-effective?

To put in simple words, cost effectiveness of a drug is generally ‘expressed in terms of a ratio where the denominator is a gain in health from a measure (years of life, premature births averted, sight-years gained) and the numerator is the cost associated with the health gain.’

From this perspective, a January 2015 research study titled, “Pricing In The Market For Anticancer Drugs”, published by the National Bureau Of Economic Research of the United States observed that anticancer drugs like bevacizumab (US$ 50,000 per treatment episode) and ipilimumab (US$120,000 per episode) have fueled the perception that the launch prices of anticancer drugs are fast increasing over time.

To evaluate the pricing trend of these drugs, the researchers used an original dataset of 58 anticancer drugs, approved between 1995 and 2013, and found that launch-prices, adjusted for inflation and drugs’ survival benefits, increased by 10 percent, or about US$ 8,500, per year. This study was restricted to drugs administered with the primary intent of extending survival time for cancer patients and drugs for which survival benefits have been estimated in trials or modeling studies. The researchers did not consider drugs administered to treat pain or drugs that are administered to alleviate the side effects of cancer treatments.

The paper concluded, as compared to the older ones, newer anticancer treatments, generally, are less cost-effective. Despite this fact, the prices of these drugs are rising faster than their overall effectiveness.

How much do these drugs cost to prolong a year of life for cancer patients?

Another paper, titled “Cancer Drugs Aren’t As Cost-Effective As They Used To Be”, published in the Forbes magazine on September 30, 2015, expressed serious concern on the declining cost-effectiveness of new anticancer drugs. The author termed this trend as unacceptable, and more disturbing when providing just a year of life to cancer patients costs around US$ 350,000 to even US$ 800,000. High prices should reflect large benefits, and we need to demand value out of medical interventions – he recommended.

Do the claims of efficacy also reflect the real-world effectiveness?

Providing an answer to this question, a very recent article titled, “Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer Medicines”, published in the well reputed medical journal ‘JAMA Oncology’ on December 29, 2016, concluded as follows:

“Although innovation in the oncology drug market has contributed to improvements in therapy, the magnitude and dimension of clinical benefits vary widely, and there may be reasons to doubt that claims of efficacy reflect real-world effectiveness exactly.”

As stated above, this conclusion was drawn by the researchers after a detail study on the overall survival, quality of life, and safety benefits of recently licensed cancer medicines, as there was a dearth of evidence on the impact of newly licensed cancer medicines.

The authors analyzed in detail health technology assessment reports of 62 cancer drugs approved in the United States and Europe between 2003 and 2013, and found that these were associated with increased overall survival by an average of 3.43 months between 2003 and 2013. Following is a summary of the detail findings:

  • 43 percent increased overall survival by 3 months or longer
  • 11 percent by less than 3 months
  • 30 percent was not associated with any increase in overall survival, which means almost one third of these drugs lacked evidence to suggest their increased survival rate when compared to alternative treatments
  • Most new cancer drugs, though improved quality of life, were associated with reduced patient safety

The researchers expect this study to support clinical practice, and promote value-based decision-making in the cancer drug treatment, besides assessing their cost-effectiveness.

Some overseas Cancer Institutes protested:

In 2012, doctors at the Memorial Sloan-Kettering Cancer Center reportedly announced through ‘The New York Times’ that their hospital would not be using Zaltrap, a newly patented colorectal cancer drug at that time, from Sanofi. This action of the Sloan-Kettering doctors compelled Sanofi to cut the price of Zaltrap by half.

Unlike India, where prices of even cancer drugs do not seem to be a great issue with the medical profession, just yet, the top cancer specialists of the American Society of Clinical Oncology are reportedly working out a framework for rating and selecting cancer drugs not only for their benefits and side effects, but prices as well.

In a 2015 paper, a group of cancer specialists from Mayo Clinic also articulated, that the oft-repeated arguments of price controls stifle innovation are not good enough to justify unusually high prices of these drugs. Their solution for this problem includes value-based pricing and NICE like body of the United Kingdom.

This Interesting Video from Mayo Clinic justifies the argument.

Was it a tongue-in-cheek action from India?

On March 9, 2012, India did send a signal to global pharma players on its apparent unhappiness of astronomical pricing of patented new cancer drugs in the country. The then Indian Patent Controller General, on that day, issued the first ever Compulsory License (CL) to a domestic drug manufacturer Natco, allowing it to sell a generic equivalent of a kidney cancer treatment drug from Bayer – Nexavar, at a small fraction of the originator’s price.

However, nothing has changed significantly since then on the ground for cancer drugs in the country. Hence, many construe the above action of the Government no more than mere tokenism.

In this context, it won’t be out of place recapitulating an article, published in a global business magazine on December 5, 2013 that quoted Marijn Dekkers, the then CEO of Bayer AG as follows:

“Bayer didn’t develop its cancer drug, Nexavar (sorafenib) for India, but for Western Patients that can afford it.”

Whether, CL is the right approach to resolve allegedly ‘profiteering mindset’ at the cost of human lives, is a different subject of discussion.

VBP concept is gaining ground: 

The concept of ‘Value-Based Pricing (VBP)’, has started gaining ground in the developed markets of the world, prompting the pharmaceutical companies generate requisite ‘health outcome’ data using similar or equivalent products.

Cost of incremental value that a product delivers over the existing ones, is of key significance, and should always be the order of the day. Some independent organizations such as, the National Institute for Health and Clinical Excellence (NICE) in the UK have taken a leading role in this area.

Intriguingly, in India, public health related issues, however pressing these are, still do not seem to arrest much attention of the government to provide significant relief to a large majority of population in the country.

Conclusion:

Warren Buffet – the financial investor of global repute once said, “Price is what you pay. Value is what you get.” Unfortunately, this dictum is not applicable to the consumers of high priced life-saving drugs, such as, for cancer.

Prices of new drugs for the treatment of life-threatening ailments, such as cancer, are increasingly becoming unsustainable, across the world, and more in India. As articulated by the American Society of Clinical Oncology in 2014, this is mainly because their prices are disconnected from the actual therapeutic value of products.

Currently, a sizable number of poor and even middle-income patients, who spend their entire life’s saving for treatment of a disease like cancer, have been virtually priced out of the patented new cancer drugs market.

The plight of such patients is worse in India, and would continue to be so, especially when no trace of Universal Health Care/Coverage (UHC) is currently visible anywhere near the healthcare horizon of the country.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Dry New Antibiotic Pipeline: Increasing Incidence Of Deadly Antibiotic Resistance

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On January 13, 2017, ‘The Telegraph’ quoting the ‘Centers for Disease Control and Prevention (CDC)’ reported that a woman in Nevada was killed by a superbug that proved resistant to every antibiotic available in the United States (US). She was in her 70s, and had recently returned to the US after an extended visit to India. The CDC found her blood containing ‘New Delhi metallo-beta-lactamase (NDM)’ – an enzyme that was first detected in India, makes bacteria resistant to many antibiotics. Nevertheless, this is just not a solitary example. It’s fast giving rise to a snowballing effect.

The magnitude of this problem has now assumed a global dimension. A May 2016 review of ‘Antimicrobial Resistance (AMR)’ estimates: ‘By 2050, 10 million lives a year and a cumulative 100 trillion USD of economic output is at risk due to the rise of drug – resistant infections, if we do not find proactive solutions now to slow down the rise of drug resistance. Even today, 700,000 people die of resistant infections every year.

According to the World Health Organization (W.H.O), AMR is the ability of a microorganism (like bacteria, viruses, and some parasites) to stop an antimicrobial (such as antibiotics, antivirals and antimalarials) from working against it. Consequently, standard treatments become ineffective, infections persist and may spread to others.

As antibiotics are a special category of antimicrobial drugs that underpin modern medicine as we know it: if they lose their effectiveness, key medical procedures (such as gut surgery, caesarean sections, joint replacements, and treatments that depress the immune system, such as chemotherapy for cancer) could become too dangerous to perform. Most of the direct and much of the indirect impact of AMR will fall on low and middle-income countries – the above review reiterates.

The first global report on AMR:

Not so long ago, In 2014, the first global report on AMR, published by the W.H.O reiterated that this scary scenario is no longer a prediction for the future. It is happening right now, and is not a country specific issue, but a global concern that is jeopardizing global health security.

“Hundreds of thousands of antibiotic-resistant infections and tens of thousands of related deaths go uncounted each year. But even if they were closely tracked, the lack of new drugs to meet the rising tide of resistance means the toll will only mount,” Reported Reuters in another article titled “Stronger superbugs and no new drugs to fight them”, on December 15, 2016.

Thus, there isn’t even an iota of doubt now that in the battle against bacterial infections, drug-resistant superbugs are fast emerging as one of the deadliest issues in the health care space, across the world, including India.

Interestingly, no one knows who will fall victim of this scary scenario and when. Neither can one eliminate this risk completely, even in the developed world. Only painstaking medical research, sans sole focus on creamy bottom-line, and with the application of cutting edge technology, can help overcome this fast-growing health menace to mankind.

“It’s all about the bottom line”:

Quoting a biochemistry professor at Indiana University, Bloomington, the above article reported, in 1980, 36 large American and European pharmaceutical companies were involved in research into new antibiotics. This number currently reduces to just four: Novartis AG, Merck & Co, GlaxoSmithKline Plc and Sanofi SA.

The May 2016 Data Table of ‘The Pew Charitable Trust’ indicates, as of March 2016, an estimated 37 new antibiotics with the potential to treat serious bacterial infections are in clinical development for the U.S. market. It is worth noting, the success rate of clinical drug development is low. Historical data show that, generally, only 1 in 5 infectious disease products that enter human testing (phase 1 clinical trial) will be approved for patients.

Moreover, most of these new antibiotics are based on existing drugs. Although, this approach is cheaper and easier to develop a new antibiotic, as compared to new classes of drugs, bacteria may rather quickly succeed in developing resistance to them.

It keeps happening, primarily because the return on investment for antibiotics, which are typically prescribed for a short period of 7 to 14 days, is much lower than the new drugs used for virtually a life treatment of chronic conditions, such as hypertension, hyperlipidemia, or diabetes.

Consequently, most of the constituents of Big Pharma have virtually fled the antibiotic business, as the new drug development ball game today “is all about the bottom line”, the article quoted.

Antibiotic resistance in India:

As W.H.O articulates in its above report, AMR poses a greater challenge in the developing nations, such as India, where the burden of infectious disease is high and health care spending is too low. The problem assumes a more critical dimension in India, that records among the highest bacterial disease burden in the world, with antibiotics playing a critical role in limiting morbidity and mortality.

The 2015 multi-country survey of the W.H.O unveiled a widespread public misunderstanding about antibiotic usage and resistance in India. Some of the major highlights are as follows:

  • Three quarters (75 percent) of respondents think, incorrectly, that colds and flu can be treated with antibiotics, and only 58 percent know that they should stop taking antibiotics only when they finish the course as directed.
  • More than three quarters (76 percent) of respondents report having taken antibiotics within the past 6 months; 90 percent say they were prescribed or provided by a doctor or nurse.
  • While 75 percent agree that antibiotic resistance is one of the biggest problems in the world, 72 percent of respondents believe experts will solve the problem before it becomes too serious.

Nowhere AMR is as stark as in India:

Another article published in the ‘PLOS Medicine’ on March 2, 2016, is quite in tune with the above W.H.O report. It also reiterates that antibiotic resistance is a global public health threat, but nowhere is it as stark as in India. The crude infectious disease mortality rate in India today is 416.75 per 100,000 persons and is twice the rate prevailing in the United States when antibiotics were introduced (roughly 200 per 100,000 persons).

It also captures the following burning issues in this area:

  • Antibiotic use is a major driver of resistance. In 2010, India was the world’s largest consumer for human health.
  • Access to antibiotics is rising, which portends well for the large proportion of India’s population that thus far had poor access to these life-saving drugs.
  • The convergence of factors such as poor public health infrastructure, rising incomes, a high burden of disease, and cheap, unregulated sales of antibiotics have created ideal conditions for a rapid rise in resistant infections in India.
  • Over-the-counter, nonprescription sales of carbapenems in India are among the highest in the world, and contribute to growing carbapenem resistance among gram-negative organisms.
  • Improving regulations of drug production and sales, better managing physician compensation, and encouraging behavior change among doctors and patients, are of immediate priority.

More serious than local perception:

The new report released by the Center for Disease Dynamics, Economics & Policy (CDDEP) in September 2015, has flagged an alarming trend of bacterial resistance to last-resort antibiotics that can lead to life-threatening infections across the world.

While the developed countries still use far more antibiotics per capita, high AMR rates in the developing nations, such as India, Kenya and Vietnam send a strong warning signal to the world.

For example, in India, 57 per cent of the infections caused by Klebsiella pneumoniae, a deadly superbug found in hospitals, were found to be resistant to one type of last-resort drug in 2014 – an increase from 29 per cent in 2008. It is worth noting that these drugs, known as carbapenems, are still effective against Klebsiellainfections in 90 per cent of cases in the U.S, and over 95 per cent in Europe.

A new class of antibiotics discovered with iChip technology:

The good news is, as reported in the June 18, 2015 issue of the Journal of Antimicrobial Chemotherapy, scientists could produce a new class of antibiotic, named Teixobactin, from a hitherto undescribed soil microorganism (provisionally named Eleftheria terrae). It was isolated with a new tool – the iChip, that allowed the environmental bacterium to grow and for the antibiotic it produced to be isolated and subsequently identified.

Working together with collaborators at the University of Central Florida and the Hong Kong Polytechnic University, a research team of Hong Kong University (HKU) has successfully synthesized this ‘game-changing’ antibiotic that can kill a wide range of bacteria seemingly without developing resistance.

Teixobactin has activity against Gram-positive (but not Gram-negative) organisms and mycobacteria and a novel mode of action inhibiting peptidoglycan biosynthesis. Teixobactin, a still-experimental drug that may herald a new era of antibiotic discovery. However, there are no guarantees that it will be able to reach the market post regulatory acid tests, though the use of the iChip will hopefully result in the discovery of further potential new antibiotics.

Country specific frugal innovation is also necessary:

Alongside, various academic initiatives in search of new, path breaking antibiotics, frugal innovation in various countries to address the local issues in this area, could also play a very significant role to contain this menace.

In this context, I shall quote from the example of a small country, such as Singapore, which is contributing significantly to medical research and development in this area.

An article published in a new daily of Singapore – ‘Today’, on December 29, 2016, highlighted that drug-resistant superbugs have become one of the most pressing problems in the healthcare space of even one of the cleanest cities of the world.

Driven by the need to find a more suitable alternative, researchers at the Institute of Bioengineering and Nanotechnology (IBN) of Singapore, have developed a new material that can kill E coli bacteria within seconds. E coli is a type of bacteria found in the intestines of humans and animals, and some strains can cause severe diarrhea, abdominal pain and fever.

The article, reported that the novel synthetic material, known as imidazolium oligomers, can kill 99.7 percent of the bacteria within 30 seconds, more rapidly than any existing antimicrobial product on the market, such as hand wash or surface sprays. Existing products take minutes to hours to kill the bacteria. It was also tested and found to be effective against other common strains of antibiotic-resistant bacteria and fungi, such as Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. It has been licensed by a multinational firm for commercial development in October.

If Singapore can take its own initiatives in this crucial health care space, why can’t India?

Conclusion:

Strict enforcement of the existing regulations of the medical sector, particularly in the prescription of medicines, is of crucial importance. Lack of knowledge among medical practitioners, as well as public on rational use of antibiotics, aggravates the issue.

Notwithstanding fast drying-up of global research pipeline for new antibiotics due to several reasons, India needs to address this fast escalating life-threatening problem through various other practical means. One such could be, putting in place a comprehensive National Action Plan for AMR, quite in line with the Global one, which the W.H.O has already recommended.

This critical issue gets further compounded, as a very significant part of an out-of-pocket expenditure on health care is on medicines, and longer treatment with ineffective drugs and/or second line expensive antibiotics, are pushing the treatment costs higher. On the other side, higher priced drug regimens are less likely to be adhered to, which again contributes to the AMR.

“This situation needs to be interrupted and reversed, not only for safeguarding people’s health, but also for providing protection against health care costs and people going into poverty,” advises the premier World Health body.

Finally, it is important for all to bear in mind, no one knows who will fall victim of this scary scenario and when. So, a decisive action from all concerned can’t wait any longer.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Mental Health Problem: A Growing Concern In The Healthcare Space Of India

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A thud!

Something fell from high above!

In no time, a bright young life of just a 32-year-old highly accomplished professional – a widely admired soul, vanished in the thin year, for good, mostly unnoticed in the quiet neighborhood, initially.

The news was more than a shock to my family. It engulfed me by the fire of impotent rage against this cruel play of destiny, where nothing can be undone, just nothing!

What prompted this so bright, successful, hugely promising and an ever-helpful-to-all guy doing what he did? No one could ferret out the answer, just yet, and possibly would never be.

Medical literatures have now established a close relationship between depression and its possible lethal outcome – suicide. Using literature data, one can estimate that 60 to 70 percent of the subjects attempting suicide were suffering from depression of various kinds. Was this young man too silently suffering from this undiagnosed and untreated mental illness?

In this article, I shall dwell on this important aspect of overall health care in India.

Depression ranks 4th in the 10 leading causes of the global burden of disease:

The World Health Organization (W.H.O) underlines: “Major depression is now the leading cause of disability globally and ranks fourth in the ten leading causes of the global burden of disease. If projections are correct, within the next 20 years, depression will have the dubious distinction of becoming the second cause of the global disease burden. Globally, 70 million people suffer from alcohol dependence. About 50 million have epilepsy; another 24 million have schizophrenia. A million people commit suicide every year. Between ten and 20 million people attempt it.”

A recent study:

Currently in India, millions of people with mental illnesses continue to remain untreated. This is vindicated by a chain of recent research studies titled, “China-India Mental Health Alliance Series”, published in ‘The Lancet’ on May 18, 2016.

The studies highlighted that: “China and India, which together contain 37 percent of the world’s population, are both undergoing rapid social changes. Because mental disorders account for a high proportion of morbidity, detailed knowledge of the mental health status of the populations in these two countries, and the evidence-base regarding the treatment of those disorders, are of paramount concern.”

“In China, mental, neurological and substance use disorders accounted for 7 percent of all (years of healthy life of the whole population) in 1990, rising to 11 percent by 2013. Similarly, in India, the proportion of all burden explained by mental, neurological, and substance use disorders rose from 3 percent in 1990 to 6 percent in 2013,” the researchers highlighted.

Greater concern in India:

In 2013, 36 million years of healthy life were lost to mental illness in China, and 31 million in India. The new research estimates that by 2025, though 36.9m years of healthy life will be lost to mental illness in China (10 percent increase), it will be 38.1m in India (23 percent increase). Anxiety and depression are the most common mental health problems among working age adults between 20 and 69 years.

Similarly, dementia is emerging as a growing mental health issue for both countries. However, from 2015 to 2025, it is estimated that the number of healthy years lost due to dementia will increase by 82 percent in India against 56 percent in China.

Interestingly, in August 2016, replying to a debate on the ‘Mental Health Care Bill’ in the Parliament, the Union Health Minister Mr. J. P. Nadda said, around 6-7 per cent of Indian population suffered from mental illnesses, while 1-2 per cent suffer from acute mental disease.

This means, over 70 million people are affected by mental illness in India, which has a close association with the rate of suicides, cardiovascular disorders, and loss of a significant number of productive days. It is estimated that around 50 percent of people with severe mental disease and around 90 percent of those with less severe symptoms, remain untreated in the country.

Depression, reportedly, the most prevalent form of mental illness that affects almost 3 to 5 percent of urban population living in cities, such as, Mumbai or Delhi. Around 30 percent of them are severely neurotic.

Alzheimer’s disease was reported to be the most common of severe disorders (54 percent) followed by vascular dementia (39 percent).

Another Government statistics indicate that 20 percent of Indians reportedly need counselling at some point of their lives. One per cent of the population suffers from serious mental health disorders, while 5-10 percent of Indians suffer from moderate disorders.

Another recent study:

Another recent report published in ‘The Lancet Psychiatry’ on 12 August 2016, captured the following details for India, in this area:

  • Very few population-representative data were found for mental disorders, with an average coverage of just 1 percent of the country’s population.
  • Major depressive disorder, anxiety disorder, and alcohol dependence were the most common mental, neurological, and substance abuse disorders, for men.
  • For women, anxiety disorder, major depressive disorder, and dysthymia were most common.
  • Human and financial resources for mental health are grossly inadequate with less than 1 percent of the national health care budget allocated to mental health in India.
  • Improvement of coverage will need to address both supply-side barriers and demand-side barriers related to stigma and varying explanatory models of mental disorders.

An associate professor of psychiatry at New Delhi’s All India Institute of Medical Sciences (AIIMS), reportedly said, there is just one psychiatrist for every 400,000 Indians. Apparently, he also said that there are only about 4,000 psychiatrists, 1,000 psychologists and 3,000 social workers in the entire country of over 1.2 billion people. Only 1,022 college seats for mental health professionals are set aside in India.

Or, in other words, a huge dearth of trained mental health professionals, coupled with low public investments, and fueled by high associated stigma, continue to compel many Indian populations lose many years of their lives to the illness.

Role of traditional medicines:

The study also suggests that traditional medicine practitioners, who are so common in India, “may be trained to recognize and refer patients who are at risk to themselves and others, or to advise patients against stopping their medication. Nevertheless, the authors do call for more research in this area to understand the effectiveness and potential risks of traditional medicines in the treatment and management of mental health.

Associated stigma:

It’s worth repeating, unlike many developed countries of the world, there is still a stigma associated with mental health problems in India. There are several instances of its adverse impact, not just on the social level, but also on the employment opportunities. These issues compound the treatment problem, making their public interaction too very weird at times, further increasing social polarization and inequalities.

Not a personal failure:

As the World Health Organization (W.H.O) articulates: “Mental illness is not a personal failure. It doesn’t happen only to other people. We all remember a time not too long ago when we couldn’t openly speak about cancer. That was a family secret. Today, many of us still do not want to talk about AIDS. These barriers are gradually being broken down.”

The Mental Health Care Bill:

The long-awaited ‘Mental Health Care Bill’, which after an extensive consultation process, is now awaiting the lawmakers’ formal approval for its enactment as law. The Bill, was passed by the Rajya Sabha on August 8, 2016, and is expected to be discussed in the Lok Sabha, probably in this budget session. It was first introduced on August 19, 2013, the Rajya Sabha Standing Committee report was submitted on November 20, 2013.

The bill reportedly redefines mental illness to better understand various conditions that are persistent among the population. It states that mental illness is a ‘substantial disorder of thinking, mood, perception, orientation or memory that grossly impairs judgement, behavior, capacity to recognize reality or ability to meet the ordinary demands of life’. Mental conditions related to alcohol or drug abuse are also included in the definition.

The Bill basically aims at protecting the rights of persons with mental illness and promote their access to mental health care.

One of the major highlights of the bill is decriminalization of attempt to suicide, as it states that the person attempting suicide will be presumed to be ‘under severe stress’ unless otherwise proven, and is not punishable. This move is commendable, ‘as it takes away the burden of implicating a mentally ill person in a crime that he or she had no sane control over.’ The W.H.O report on suicides (2000-2012) puts India right on top of the list in Southeast Asia. It says, the average suicide rate in India is 10.9 for every 100,00 people.

Conclusion:

Mental health has now been included in the United Nation’s ‘Sustainable Development Goals (SDG)’ at its General Assembly in September 2015. It is very likely that SDGs addressing mental health issues will become a part of country development plans and of bilateral and multilateral development assistance. This could well mean that millions of people will finally receive much needed help in this area.

Zeroing-in to India, mental health problems have since been a low priority area in the public health narrative of the country. The health information system of the country does not prioritize mental health, either.

To address this growing concern, besides forthcoming enactment of ‘Mental Health Care Bill’, the much-awaited healthcare reform of the nation, should include a transparent policy framework for mental health. A substantial number of community health workers, including traditional medicine practitioners need to be trained to deliver basic mental health hygiene and care. More serious cases, in that process, should be referred to the qualified professionals.

Mental health problems are growing at a rapid pace in India, being a cause of great concern in the healthcare space in India. It deserves to be treated like any other serious physical illness or disease, in a systematic way, backed by adequate budgetary support for affordable treatment and counselling measures, wherever required.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Sharper Focus On Vaccine: A Huge Scope To Reduce Disease Burden In India

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Several international research studies have conclusively established that the aggressive application of nationally recommended prevention activities could significantly reduce the burden of disease in several areas. Immunization or vaccination program is one such critical areas.

Several ailments, which used to be so common all over the world, can now be effectively prevented through vaccination. The most common and serious vaccine-preventable diseases are: diphtheria, Haemophilus influenzae serotype b (Hib), hepatitis B and C, measles, meningitis, mumps, pertussis, poliomyelitis, rubella, tetanus, tuberculosis, rotavirus, pneumococcal disease and yellow fever.  The list of the World Health Organization (WHO) indicates that vaccines are now available for 25 different diseases.

Thus, vaccination can save millions of lives and morbidity that such diseases still cause to a very large number of global population. Thanks to vaccines, two most scary diseases – small pox (totally) and polio (almost totally), have been eliminated from the world.

No doubt, why vaccination was voted as one of the four most important developments in medicine of the past 150 years, alongside sanitation, antibiotics and anesthesia by readers of the ‘British Medical Journal (BMJ)’ in 2007. It has been decisively proved that vaccines are one of the most successful and cost-effective public health interventions, which help preventing over 3 million deaths every year, throughout the world, topping the list in terms of lives saved.

In tandem, concerted efforts need to be made by both the industry and the Governments to improve affordable access to all these vaccines for a larger section of the population, especially in the developing world.

A crying need still exists:

Nevertheless, there is still a crying need for greater encouragement, more resource deployment and sharper focus towards newer vaccine development for many more dreaded and difficult diseases. One such area is malaria vaccine.

Some areas of new vaccine development:

Following is an example of some newer therapy areas where novel vaccines are now reportedly under development:

  • Malaria vaccine
  • Cancer vaccine
  • AIDS
  • Alzheimer’s disease

Malaria vaccine:

A July 24, 2015 article of the BBC News states, the ‘European Medicines Agency (EMA)’ gave a positive scientific opinion after assessing the safety and effectiveness of the first anti-malarial vaccine of the world – Mosquirix, developed by the British pharma major GlaxoSmithKline.

The vaccine reportedly targets the ‘P. falciparum’, the most prevalent malaria parasite and the deadlier of the two parasites that transmit the disease. At present, in the absence of any licensed vaccines for malaria, the main preventive measures to contain the spread of this parasitic disease are spraying of insecticides, use of other mosquito repellent and mosquito nets.

However, it was observed during its clinical trial that he best protection with this vaccine was achieved among children aged five to 17 months, receiving three doses of the vaccine a month apart, plus a booster dose at 20 months. In this group, cases of severe malaria were cut by a third over a four-year period, the report said.

Some concern was also expressed, as the effectiveness of the vaccine waned over time, making the booster shot essential, without which the vaccine did not cut the rate of severe malaria over the trial period. Moreover, the vaccine did not prove very effective in protecting young babies from severe malaria.

This caused a dilemma for the ‘World Health Organization (WHO)’. On the one hand, the stark reality of malaria killing around 584,000 people a year worldwide, and on the other, lack of conclusiveness in the overall results for this vaccine. Therefore, the world health body decided at that time to further consider about it, soon after the experts’ deliberation on whether to recommend it for children, among whom trials have yielded mixed results, gets completed.

The good news is, on November 18, 2016, Newsweek reported the announcement of the W.H.O, that Mosquirix will be piloted across sub-Saharan Africa in 2018, after a funding approval of US$ 15 million for this purpose.

Cancer vaccines:

According to the National Cancer Institute, which is a part of the National Institutes of Health (NIH) of the United States, cancer vaccines belong to a class of substances known as biological response modifiers. Biological response modifiers work by stimulating or restoring the immune system’s ability to fight infections and disease. There are two broad types of cancer vaccines:

  • Preventive (or prophylactic) vaccines, which are intended to prevent cancer from developing in healthy people.

-       Persistent infections with high-risk human papillomavirus (HPV) types can cause cervical cancer, anal cancer, oropharyngeal cancer, and vaginal, vulvar, and penile cancers. Three vaccines are approved by the US Food and Drug Administration (FDA) to prevent HPV infection: Gardasil®, Gardasil 9®, and Cervarix®.

-       Chronic Hepatitis B virus (HBV) infection can lead to liver cancer. The FDA has approved multiple vaccines that protect against HBV infection, such as, Engerix-B and Recombivax HB, which protect against HBV infection only.

  • Treatment (or therapeutic) vaccines, which are intended to treat an existing cancer by strengthening the body’s natural immune response against the cancer. Treatment vaccines are a form of immunotherapy.

-       In April 2010, the USFDA approved the first cancer treatment vaccine. This vaccine, sipuleucel-T (Provenge®), is approved for use in some men with metastatic prostate cancer. It is designed to stimulate an immune response to prostatic acid phosphatase (PAP), an antigen that is found on most prostate cancer cells.

Another type of cancer vaccine is currently being developed, known as the Universal Cancer Vaccine.

  • Universal Cancer Vaccine,  June 1, 2016 issue of ‘The Independent’ reported that scientists of Johannes Gutenberg University in Germany have taken a “very positive step” towards creating a universal vaccine against cancer that makes the body’s immune system attack tumors as if they were a virus. The researchers had taken pieces of cancer’s genetic RNA code, put them into tiny nanoparticles of fat and then injected the mixture into the bloodstreams of three patients in the advanced stages of the disease. The patients’ immune systems responded by producing “killer” T-cells designed to attack cancer.

The vaccine was found to be effective in fighting “aggressively growing” tumors in mice. At the same time, such vaccines are fast and inexpensive to produce, and virtually any tumor antigen (a protein attacked by the immune system) can be encoded by RNA, the report said.

The analysts forecast the global cancer vaccines market to grow at a CAGR of 27.24 percent over the period 2014-2019.

HIV/AIDS Vaccine:

The 21st International AIDS Conference (AIDS 2016) held in Durban, South Africa from July 18 to 22, 2016, revealed that a vaccine against HIV will be trialed in South Africa later in 2016, after meeting the criteria needed to prove it, could help fight the epidemic in Africa. A small trial, known as HVTN100, took place in South Africa in 2015 to test the safety and strength of immunity the vaccine could provide, ahead of any large-scale testing in affected populations.

This development reportedly has its origin in a large landmark 2009 trial of RV 144 vaccine in Thailand, demonstrating the proof of concept that a preventive vaccine with a risk reduction of 31 percent could effectively work.  The trial was supported by the World Health Organization (WHO) and UNAIDS. The clinical trial participants who received Vacc-4x, reportedly “experienced a 70 percent viral load decrease relative to their level before starting Anti-Retroviral Therapy (ART), compared with no notable reduction among placebo recipients.”

Alzheimer’s disease vaccine:

A vaccine for Alzheimer’s disease could be trialed in human within the next 3-5 years, after researchers from the United States and Australia have uncovered a formulation that they say successfully targets brain proteins, which play a role in the development and progression of the disease, states a July 18, 2016 report published in the ‘Medical News Today (MNT)’.

This vaccine generates antibodies that target beta-amyloid and tau proteins in the brain – both of which are considered hallmarks of Alzheimer’s disease. In their study, the researchers found that the formulation was effective and well-tolerated in Alzheimer’s mouse models, with no reports of adverse reactions. The vaccine was also able to target the proteins in brain tissue from patients with Alzheimer’s.

Study co-author Prof. Michael Agadjanyan, Institute for Molecular Medicine, California said: “This study suggests that we can immunize patients at the early stages of AD (Alzheimer’s disease), or even healthy people at risk for AD, using our anti-amyloid-beta vaccine, and, if the disease progresses, then vaccinate with another anti-tau vaccine to increase effectiveness.”

If the vaccine continues to show success in these preclinical trials, the researchers envisage that they could be testing the vaccine in individuals at high risk for Alzheimer’s, or those in the early stages of the disease, within the next 3-5 years.

More details on vaccine development:

A 2012 report on vaccines, published by the Pharmaceutical Research and Manufacturers of America (PhRMA) give details of vaccines under development.

Vaccine requirements of the developing world: 

Developing countries of the world are now demanding more of those vaccines, which no longer feature in the immunization schedules of the developed nations. Thus, to supply these vaccines at low cost will be a challenge, especially for the global vaccine manufacturers, unless the low margins get well compensated by high institutional demand.

Issues and challenges:

To produce a safe, effective and marketable vaccine, besides R&D costs, it takes reportedly around 12 to 15 years of painstaking research and development process.

Moreover, one will need to realize that the actual cost of vaccines will always go much beyond their R&D expenses. This is mainly because of dedicated and highly specialized manufacturing facilities required for mass-scale production of vaccines, and then for the distribution of the same mostly using cold-chains.

Around 60 percent of the production costs of vaccines are fixed in nature (National Health Policy Forum. 25. January 2006:14). Thus, such products will need to have a decent market size to be profitable. Unlike many other medications for chronic ailments, which need to be taken for a long duration, vaccines are administered for a limited number of times, restricting their business potential.

Thus, the long lead time required for the ‘mind to market’ process for vaccine development together with high cost involved in their clinical trials/marketing approval process, special bulk/institutional purchase price and limited demand through retail outlets, restrict the research and development initiatives for vaccines, unlike many other pharmaceutical products.

Besides, even the newer vaccines will mostly be required for the diseases of the poor, like Malaria, Tuberculosis, HIV and ‘Non-Communicable Diseases (NCDs)’ in the developing countries, which may not necessarily guarantee a decent return on investments for vaccines, unlike many other newer drugs. Thus, the key issue for developing a right type of newer vaccine will continue to be a matter of pure economics.

India needs a vibrant vaccine business sector:

For a greater focus on all important disease prevention initiatives, there is a need to build a vibrant vaccine business sector in India. To achieve this objective the government should create an enabling ecosystem for the vaccine manufacturers and the academics to work in unison. At the same time, the state funded vaccine R&D centers should be encouraged to concentrate more on the relevant vaccine development projects, ensuring a decent return on their investments for long-term economic sustainability.

Often, these stakeholders find it difficult to deploy sufficient fund to take their vaccine projects successfully through various stages of clinical development to obtain marketing approval from the drug regulator, while earning a decent return on investments. This critical issue needs to be urgently addressed by the Government to make the disease prevention initiatives in the country sustainable.

A possible threat to overcome: 

As per reports, most Indian vaccine manufacturers get a major chunk of their sales revenue from exports to UN agencies, charitable organizations like, the Bill & Melinda Gates Foundation, GAVI, and other country-specific immunization programs.

The report predicts, the virtual monopoly that Indian vaccine manufacturers have enjoyed in these areas, will now be challenged by China, as for the first time in 2012, the Chinese national regulatory authority received ‘pre-qualification’ certification of WHO that allows it to approve locally manufactured vaccines to compete for UN tenders.

Conclusion:

Keeping this in perspective, vaccine related pragmatic policy measures need to be taken in the country for effective disease prevention, covering all recommended age groups, of course, with an equal focus on their effective implementation, without delay. Consequently, this will not only help reduce the disease burden in the country, but also provide the much-awaited growth momentum to the vaccine market in India.

Alongside, increasing number of modern imported vaccines coming in, would help India address one of its key healthcare concerns effectively, and in a holistic way.

It is about time to aggressively garner adequate resources to develop more modern vaccines in the country. In tandem, a rejuvenated thrust to effectively promote and implement vaccine awareness campaigns, would help immensely in the nation’s endeavor for disease prevention with vaccines, that offers a huge scope to reduce disease burden, for a healthier India.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Awaiting The Two To Tango: Pharma Innovation And Public Health Interest

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“The rewards for the breakthrough drug discovery must be substantial, but if prices are the only mechanism through which returns on research flow, affordability will be compromised,” articulated an article titled, ‘Pharmaceutical Policy Reform – Balancing Affordability with Incentives for Innovation’, published in The New England Journal of Medicine (NEJM) on February 25, 2016.

The article arrived at this conclusion, on the backdrop of the high prices of prescription drugs becoming an issue of paramount concern, not just in the United States, but across the world. This concern is so acute that it found its way into policy proposals from both the prime candidates, in the American Presidential election held on November 8, 2016.

Through last several decades, healthcare sector in general and particularly the pharmaceutical industry, witnessed many innovations that cure and effectively manage ailments to improve the general quality of life. It enormously impacted the lives of many in the developed countries, and a few others which offer high quality Universal Health Care in a comprehensive format, for all.

A trickle-down impact:

Nevertheless, even no more than its just a trickle-down impact, helped increase overall life expectancy of the population in many developing and poor countries, mostly driven by the expanding number of cheaper generic drugs, fueled by more treatment and disease management options.

The paper titled, ‘World Population Prospects – The 2015 Revision’ of the Department of Economic and Social Affairs, Population Division of the United Nations’ reported that the life expectancy at birth rose by 3 years between 2000-2005 and 2010-2015, that is from 67 to 70 years. All major areas shared in the life expectancy gains over this period, but the greatest increases were in Africa, where life expectancy rose by 6 years in the 2000s, after rising by only 2 years in the previous decade.

Similarly, the global life expectancy at birth is projected to rise from 70 years in 2010-2015 to 77 years in 2045- 2050 and to 83 years in 2095-2100. Africa is projected to gain about 19 years of life expectancy by the end of the century, reaching 70 years in 2045-2050 and 78 years in 2095-2100. Such increases are contingent on further reductions in the spread of HIV, and combating successfully other infectious as well as non-communicable diseases.

The availability of cheaper generics gave some respite:

Out of a total population of 7.3 billion, as the above report says, the World Bank estimated that in 2013, 767 million people still lived on less than US$ 1.90 a day. Unfortunately, despite the greater availability of a large variety of cheaper generic drugs, the basic health care remains elusive to hundreds of millions of people in the world.

What causes more concern is the fact that 6 percent of people in low and middle-income countries are tipped into or pushed further into extreme poverty because of health spending, as the June 12, 2015 report of the World Health Organization (W.H.O) and the World Bank highlights. W.H.O has estimated that over a billion population of the world still suffer from neglected tropical diseases.

How many people benefitted from pricey patented drugs?

Nevertheless, despite so much innovation in the pharma industry, access to these new drugs remains elusive to a large section of even some the most developed nations, such as the United States, as they can’t afford these high-priced drugs. The overall situation, in this regard, is going from bad to worse. For example, the March 16, 2015 study published in the Mayo Clinic Proceedings reveals that the average annual cost of cancer drugs increased from roughly US$ 10,000 prior to 2000 to an astounding over US$  100,000 by 2012.

Further, an August 31, 2015 article published in the ‘Health Affairs’ also gave examples of Biogen Idec’s multiple sclerosis drug, Tecfidera, which costs US$ 54,900 per patient per year; hepatitis C cures from Gilead Sciences, with a sticker price of $84,000 per patient; and Orkambi, a cystic fibrosis drug from Vertex Pharmaceuticals approved this month, priced at a whopping US$ 259,000 per year. A Kaiser Health Tracking Poll last July 2015 found that 73 percent of Americans find the cost of drugs to be unreasonable, and most blamed drug manufacturers for setting prices too high, the article stated.

The health care scenario in India is no better:

A study conducted by the ‘National Sample Survey Organization (NSSO)’ from January to June 2014, which was the 71st round of the ‘National Sample Survey’, and published in the ‘Health in India’ report, narrates a very gloomy picture for India, especially for a clear majority of those who incur ‘out of pocket’ expenses on medicines. The report states, out of all health expenditure, 72 percent in rural and 68 percent in urban areas was for buying medicines for non-hospitalized treatment.

Thus, many patients cannot afford health services, even when these are needed the most. As many as 68 percent of patients in urban India and 57 percent in rural areas attributed “financial constraints” as the main reason to take treatment without any medical advice, the report adds.

In this situation, the challenges that the Governments and the civil society are facing in many developing, and to some extent even in some developed countries, though for different reasons, are multi-factorial. It has been well established that the humongous global health care challenges are mostly of economic origin.

Pharma innovation benefitted the developed countries more:

A study  titled, ‘Pharmaceutical innovation and the burden of disease in developing and developed countries’ of Columbia University and National Bureau of Economic Research, to ascertain the relationship across diseases between pharmaceutical innovation and the burden of disease both in the developed and developing countries, reported that pharmaceutical innovation is positively related to the burden of disease in the developed countries but not so in the developing countries.

Making the two to tango:

These facts prompt the need to make the pharma innovation and public health interest to tango. Several suggestions have been made and initiatives taken in this direction. Some of which are as follows:

  • Responding to this need, in 2006 W.H.O created the ‘Intergovernmental Working Group on Public Health, Innovation and Intellectual Property (IGWG)’. The primary focus of IGWG is on promoting sustainable, needs-driven pharmaceutical R&D for the diseases that disproportionately affect developing countries. One positive effect of this global debate is that some global pharmaceutical companies have initiated their R&D activities for neglected tropical diseases, such as, Malaria and Tuberculosis. Many charitable organizations like, Bill & Melinda Gates Foundation and Clinton Foundation, are allocating significant funds for this purpose.
  • A paper  titled, “Optional reward for new drugs for developing countries” published by the Department of Economics, University of Calgary, Institute of Health Economics, proposed an optional reward fund for pharmaceutical innovation aimed at the developing world to the pharmaceutical companies, which would develop new drugs while ensuring their adequate access to the poor. The paper suggests that innovations with very high market value will use the existing patent system, as usual. However, the medicines with high therapeutic value but low market potential would be encouraged to opt for the optional reward system. It was proposed that the optional reward fund should be created by the governments of the developed countries and charitable institutions to ensure a novel way for access to innovative medicines by the poor.
  • ‘Open Innovation’ or the ‘Open Source Drug Discovery (OSDD)’ is another model of discovering a New Chemical Entity (NCE) or a New Molecular Entity (NME). Imbibing ‘Open Innovation’ for commercial results in pharmaceuticals, just has what has happened to android smartphones, would encourage drug discovery initiatives, especially for the dreaded disease like cancer, to make these drugs affordable for a very large section of people across the globe. In this model, all data generated related to the discovery research will be available in the open for collaborative inputs. In ‘Open Innovation’, the key component is the supportive pathway of its information network, which is driven by three key parameters of open development, open access and open source. This concept was successfully used in the ‘Human Genome Project’ where many scientists, and microbiologists participated from across the world to sequence and understand the human genes. Currently, pharmaceutical R&D is a well-protected in-house initiative of innovator global companies to maximize commercial benefits. For this reason, only a limited number of scientists working for the respective innovator companies will have access to these projects. In India, the Council of Scientific and Industrial Research (CSIR) is the champion of the OSDD movement, locally. CSIR believes that for a developing country like India, OSDD will help the common man to meet his or her unmet medical needs in the areas of mainly neglected tropical diseases.

Conclusion:

Thus, the ongoing heated debate on Innovation, Intellectual Property Rights (IPR) and Public Health Interest is gathering steam all over the globe.

Argumentative Indians are also participating in this raging debate. I reckon rightly so, as India is not only the largest democracy of the world contributing 16.7 percent of the global population, it is also afflicted with 21 percent of the global burden of disease. Considering this, the reason for similar heated debate in our country is indeed no-brainer to anyone.

Many would possibly not disagree, both encouraging innovation and safeguarding the public health interest are equally important to any society, be it in the developed nations or developing countries. Nevertheless, some constituents of ‘Big Pharma’ and their trade association still highlight that ensuring access to high price innovative drugs is the responsibility of the respective Governments. Any other regulatory mechanism to bring down such prices will be construed as a barrier to encouraging, protecting and rewarding innovation.

Be that as it may, most other stakeholders, across the world, especially the patients, are awaiting these two goals to tango. From that point, I reckon, giving a quick shape to commercially well-tested initiatives, such as, ‘Open Innovation’ model could well be an important step to ensure access to innovative new medicines for a larger number of patients of the world, meeting their unmet medical needs with greater care.

By: Tapan J Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.