Covid-19: Perils Of Haste In Scientific Decision-Making Process

Multifaceted threats posed by Coronavirus to the humanity, are getting increasingly complex, every day. Currently, Covid-19 cases in India are ‘the highest that any country has ever recorded on a single day since the start of the outbreak.’ Alongside, the hopes of billions of people – for its predictable and dependable remedies are also soaring sky high. But, despite full throttle global endeavor of scientists, the world continues waiting for scientific-evidence-based, well-proven, safe, and effective Covid-19 drugs, vaccines and other treatments.

It is expected, each of these cures and antidotes should be duly authorized by drug regulators, according to global norms – without any outside non-scientific interference – not even from the very top. Nevertheless, the reality is, as on date, besides some ‘emergency use authorizations’, all scientific pursuits in this area are Works in Progress (WIP) – some are with great potential, though.

The catastrophic impact of Covid-19 pandemic is all pervasive. So is the competition between media publications to attract maximum eyeballs, with details on many aspects of the disease and related scientific development. These include reports on intense, non-scientific pressure on scientists and regulators to make drugs, vaccines or other Covid-19 treatments immediately available for use. In this article, I shall dwell on the perils of haste in the scientific decision-making processes, while combating Covid-19.

A quick research outcome is important – based on ‘rational’ – but not ‘rash’ decisions: 

In pursuit of a quick disease treatment outcome, a rational and ethical approach in any scientific discovery process, is non-negotiable. It has always been so – while dealing with many different health crises, and should remain that way for Covid-19, as well. In my view, for achieving a prompt and desirable treatment outcome – a quick, but rational decision should always be favored – over highly influenced, contentious, non-scientific and rash decisions.

Many wise men believe, a quick decision is one, made quickly supported by irrefutable inputs of an accepted quality and scale. Whereas, a rash decision is one, made with limited, questionable or even no inputs – just based on gut feel, as it were. This broad concept is applicable to Covid-19 drugs, vaccines and other treatments, including -plasma therapy.

In the space of Covid-19 pandemic, there are several such examples, starting from hydroxychloroquine to the most recent plasma therapy – both in India, and also beyond its shores. Without being judgmental, this article will try to join some critical dots, for the readers draw their own conclusions on this issue. Let me start with two examples of this drug regulatory quagmire – the very first, and the most recent ones.

Perils of haste in the Hydroxychloroquine saga:

As I wrote in this blog that the US President Donald Trump, on March 21, 2020,  proclaimed Chloroquine and Hydroxychloroquine as potential game changers against Covid-19 global pandemic, despite doubts from the US-FDA. Interestingly, on March 28, 2020, the US drug regulator granted the emergency use authorization of these two drugs for treating Covid-19. However, it was subsequently revoked on June 15, 2020. The agency justified this action by saying:

“Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA. Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.”

The World Health Organization (W.H.O) also announced: “Studies show Hydroxychloroquine does not have clinical benefits in treating COVID-19.” However, as published by JAMA on May 28, 2020,following President Trump’s naming these drugs at a press conference, Hydroxychloroquine prescriptions shot up by over 200 percent, over the previous year. Nonetheless, the prescriptions returned to normal as news highlighting the lack of enough evidence to support its use started spreading, across the globe.

Soon, India followed the same… a strange coincidence?

As stated above, on March 21, 2020, the US President Trump proclaimed Chloroquine and Hydroxychloroquine as potential game changers against Covid-19 global pandemic, despite doubts from the US-FDA. Curiously, on March 23, 2020, Indian media also reported:

‘Amid rising Coronavirus cases in the country, the national task force for COVID-19 constituted by Indian Council for Medical Research (ICMR) has recommended hydroxy-chloroquine as a preventive medication for high-risk population. According to the advisory, it should be given to high risk population — asymptomatic healthcare workers involved in the care of suspected or confirmed cases of COVID-19 and asymptomatic household contacts of laboratory confirmed cases.’

The above protocol, recommended by the National Task Force, has been approved by the Drug Controller General of India (DGCI) for restricted use in emergency situations. This seems to have happened even before the US-FDA granted similar authorization. Intriguingly, US-FDA subsequently revoked it on June 15, 2020, for lack of enough scientific evidence, unlike the Indian drug regulator.

Another report of April 09, 2020 summed it up well. It wrote, the hype of Hydroxychloroquine – pushed by the US President Trump as a COVID-19 treatment, has now been joined by many other countries, despite inconclusive medical evidence on the efficacy and safety of the drug. Is this just a strange coincidence?

Be that as it may, India’s decision on the emergency use of Hydroxychloroquine had its rub-off financial impact in the country, in terms of increase in its export demand, which may not be an intended one, though.

Its rub-off financial impact in India:

As the world’s largest manufacturers of Hydroxychloroquine are located in India, many of these companies reaped a rich harvest in the April-June quarter, mostly, based on media reports on its use in treating Covid-19. For example, Ipca Laboratories Ltd, reportedly, garnered ₹259 Crore in additional sales, with consolidated net profit for the quarter soar threefold to ₹454 Crore, from the drug in that period.

Notably, Ipca also acknowledged, ‘HCQ sales were a one-time boost for the company. With the hype waning, after various clinical trials showed the drug did not provide any significant benefit, the company now expects sales to ease to earlier levels,’ as the report goes. Let me now move over to the most recent example.

Perils of haste in the plasma therapy saga:

Since, the third week of this month, a series of incidents related to plasma therapy highlighted the ongoing perils of haste in the scientific decision-making process. These were generally prompted by powerful non-scientific external influences, as reported below:

  • On August 23, 2020, the US President announced that the US-FDA has granted emergency approval of blood plasma from recovered Coronavirus patients as a treatment for those battling the disease. President Trump called the development “a historic breakthrough.”
  • According to Reuters, the US-FDA had authorized its use after President Donald Trump blamed the drug agency for impeding the rollout of vaccines and therapeutics for political reasons.
  • The very next day of President Trump’s announcement, on August 24, 2020, the World Health Organization advised caution about endorsing the use of recovered COVID-19 patients’ plasma to treat those who are ill, saying evidence it works remains “low quality.”
  • American scientists, including researchers at the Mayo Clinic also challenged a key statistic cited by U.S. officials as grounds for emergency approval of the treatment.
  • On August 25, 2020, US-FDA Commissioner Stephen Hahn, publicly apologized ‘for overstating the benefits of plasma for treating Covid-19 patients.’ 
  • “The US-FDA’s emergency use authorization for plasma for Covid-19 looks questionable. If this presages an early vaccine nod, we should be very afraid,” reported another article.

Similar controversy was also witnessed in India. Just days after the Drug Controller General of India (DCGI) gave its go-ahead to a proposal of ICMR for the clinical trial of convalescent plasma therapy in COVID-19 patients, the Ministry of Health said, ‘there is not enough evidence to claim plasma therapy can be used for treatment of COVID-19. Interestingly, several states, such as, Delhi, Gujarat, Maharashtra and Uttar Pradesh, have already started clinical trials for plasma-based treatment. Meanwhile, media reports, such as, ‘India sees black market boom for plasma from recovered Covid-19 patients,’ started pouring in.

Conclusion:

As recorded in the morning of August 30, 2020, total Coronavirus cases in India have reached a staggering figure of 3,542,733 with 63,657 deaths, despite all measures taken by the country. No signs of flattening of the curve are visible, just yet. In this situation, many experts believe, the way prescriptions are written for Covid-19 patients, based on anything but robust considerations, needs to be re-looked. The headline of an article, written by Richard L. Kravitz, Professor of Health Policy and Internal Medicine, University of California, Davis on July 09, 2020, vindicates this point. It said:‘When Trump pushed Hydroxychloroquine to treat COVID-19, hundreds of thousands of prescriptions followed, despite little evidence that it worked.’

Another interesting article, tried to ferret out the truth behind such haste. It voiced, ‘the truth is that researchers, academic institutions, medical journals and the media all face powerful incentives to portray the latest research findings as more earthshaking than they actually are’. The authors spotlighted, under normal circumstances, numerous mechanisms exist to blunt some of the worst over-hyping and many sources of medical information do their best to be accurate in what they report.

It is possible that in the midst of a pandemic, the urgency of the moment may overwhelm these good intentions. The above paper also cautioned, ‘Bad science can be spread far and wide by normally credible sources.” However, the bottom-line is, the scientific research community, under no circumstances, be made to comply with the thoughts and beliefs of non-scientific, but powerful decision makers. It happened in the oldest democracy in the world, as it also happened in the largest democracy on the planet earth.

The above two instances are just illustrations to highlight an important point – without becoming judgmental. The discussion spotlights the perils of haste in the scientific decision-making processes, while combating Covid-19. As many experts believe, it could be counterproductive for non-scientific power sources to influence the robust medical value creators for a quick remedy. Mainly because, patients will continue to be at the receiving end for the net outcome, of such unproven, and scientifically fragile hypes.

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.

Covid-19: Will Pharma Deliver What It Can Do The Best, Soon?

The news of a bright possibility of finding magic bullets to significantly tame, if not totally annihilate Covid-19, is coming almost every passing day. As expected, these are being initiated mostly by drug companies, alongside various academia, located in several countries of the world, including India. It rekindles hope to return to some kind of normalcy in daily life, work and business.

However, the hype created around each of these, either too early or based on some anecdotal reports, apparently driven by the desire for a windfall commercial gain, may be counterproductive. That some remedial measures to tackle the notorious virus will come very soon, could influence a number of decisions of those who are engaged in managing the situation.

The pressing need to restart the economic activity – come what may, even before the first wave of Covid-19 subsides in a developing country like, India, comes along with a strong storm signal. Balancing life with livelihood has never been so difficult ever. In tandem, it poses a great challenge also for the pharma industry to demonstrate what it stands for the society, such as:

  • Bringing scientifically proven, safe and effective drugs and vaccine, in a specified timeframe falling close to the realm of a genuine possibility.
  • Making these drugs and vaccines available, at an affordable price and accessible to all, globally.

In this article, I shall focus on the relevance of these two critical expectations of all, where, incidentally, pharma is expected to do and deliver the very best – particularly against the prevailing and near-chaotic scenario. Let me begin with the first point first.

A great challenge:

Understandably, the above task is not a piece of cake due to many reasons. For example, according to a leading pharma trade association in the United States, ‘On average, it takes at least ten years for a new medicine to complete the journey from initial discovery to the marketplace, with clinical trials alone taking six to seven years on average.’

Thus, logically, a new drug molecule for Covid-19 can’t possibly be expected, by any stretch of imagination, within the next 12 to 18 months. What one can possibly expect for the same is, repurposing older drugs for the same. Quite logically, steps are being taken in this direction. However, even for such drugs, a clinical trial would take ‘six to seven years on average.’ Considering the urgency to combat the Covid-19 pandemic, can a fair clinical trial be completed in the next 12 to 18 months?

Therefore, the challenge in hand for the drug companies, even considering a super fast-track regulatory assessment and approval in 12 to 18 months, appear a pretty tough proposition. The challenge gets more complex, if Covid-19 starts changing.

A new issue is unraveling:  

Recently, a new dimension got added to the mounting challenge of coming out with an effective drug or vaccine to fight Covid-19 pandemic, as evident from the Bloomberg article of May 20, 2020. It carries a headline ‘China’s New Outbreak Shows Signs the Virus Could Be Changing.’

It reported, Chinese doctors are seeing the Coronavirus manifest differently among patients in the new cluster of cases of their northern provinces of Jilin and Heilongjiang, compared to the original outbreak in Wuhan. Apparently, it indicates that the pathogen may be changing in unknown ways, complicating efforts to manage the infection. Although, more details need to be unraveled in this area, this incident could flag a fresh uncertainty over the virus mutation that may hinder current efforts of developing safe and effective drugs and vaccine for Covid-19.

Still no available drugs and vaccine for Covid-19 with proven clinical efficacy:

The Lancet’ article of April 02, 2020 – ‘‘Global coalition to accelerate COVID-19 clinical research in resource-limited settings’ has also emphasized the above point. It reiterated, there is still no available vaccine against Covid-19 infections and no drug with proven clinical efficacy, although there are several candidates that might be effective in prevention or treatment.

As of March 24, 2020, there were 332 COVID-19 related clinical trials, 188 of which were open for recruitment and 146 trials are preparing to recruit. These clinical trials were either planned or being carried out, mostly in China, South Korea, Europe and North America. However, not many trials were planned in south and southeast Asia, Africa, and central and South America at that time, the article pointed out. But the hype for the availability of drugs continues to reverberate, generally in the media reports. Nevertheless, the work is still in progress.

Some unproven hype as on date?

Despite so much of publicity on availability of drugs for the treatment and prevention of Covid-10, starting from Chloroquine and Hydroxychloroquine, which the US President Donald Trump called a “game changer” for Coronavirus – right up to Remdesivir, none has demonstrated scientifically proven clinical efficacy, as yet.

For example, the latest clinical trial results for Covid-19 on 15000 people, published in The Lancet on May 22, 2014 found, hydroxychloroquine and chloroquine did not benefit patients with the Coronavirus, either alone or in combination with an antibiotic. Moreover, the drugs caused an increased risk of cardiac arrhythmia. Earlier,  ‘The BMJ’ article of May 14, 2020 also found that the administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard care alone in mild to moderate Covid-19 infections. This study also noted, adverse events with the recipients of hydroxychloroquine were higher than non-recipients.

On the other hand, in India, as reported on May 23, 2020, the Union Health Ministry has issued an advisory expanding the pool of people to be given the anti-malarial drug hydroxychloroquine (HCQ) as a prophylactic to prevent them from contracting the infection.

Similarly, even Gilead had stated in its Press Release of April 29, 2020: ‘Remdesivir is not yet licensed or approved anywhere globally and has not yet been demonstrated to be safe or effective for the treatment of COVID-19,’ besides some  initial success reports. Notably, in India, Union Health Ministry has also recommended the use of anti-HIV drug combinations Lopinavir and Ritonavir for high-risk group patients, although there is no proven clinical evidence for its efficacy and safety in Covid-19 patients, if not against the use of this combination therapy.

Commercial activity progresses even before evidence-based regulatory approval:

Although, a single clinically proven drug is yet to come out, commercial activities for some of these drugs – in a near desperate situation – based apparently on hype created, including by the US President, have progressed or progressing. This had happened for hydroxychloroquine and has now started happening for remdesivir.

Almost every passing day one finds yet another repurposed drug being put on clinical trial by a different company, probably for similar reasons. There is nothing wrong on that, but which drugs work and which do not, must be evaluated in a more cohesive manner and sooner.

The good news is, the World Health Organization (WHO), which is concerned with recommendations for ‘administering unproven treatments to patients with COVID-19 or people self-medicating with them,’ has announced the “Solidarity” clinical trial for the new Coronavirus treatments. This is an international clinical trial, aimed at the scientific assessment of 4 treatment options to slow the disease progression or improve survival rate for COVID-19 patients.

Otherwise, a strong desire for people to survive – ‘somehow’, will prevail in this desperate situation, over what these medicines can actually deliver. Even drug companies never experienced in the past or even could even envisage such a pandemic at this humongous global scale.

A similar scenario is witnessed with some major vaccine development initiatives. For example, stock markets soared with the early signs of viral immune response of the much publicized experimental Covid-19 vaccine being developed by Moderna Inc. However, a few days later, after ‘parsing the data to gauge the company’s chances of success’ by the analysts, it was reported: ‘It’s too soon to assume success for Moderna Inc’s COVID-19 vaccine.’ Curiously, it continues to happen in the early days with almost all such well publicized initiatives. Nonetheless, the pursuit to find out safe, effective and clinically proven drugs and vaccine continues.

Which is why, bringing scientifically proven safe and effective drugs and vaccine sans the early hype, in a specified time, falling close to the realm of a genuine possibility, becomes a key deliverable of pharma players, in this situation. That said, it brings me to the second point where pharma and biotech companies are widely expected to meet the other expectations of all – making these drugs and vaccines available, affordable and accessible to all, globally.

Making Covid-19 drugs and vaccines available, affordable and accessible to all, globally:

Again, this seems to be an equally tough call for most drug players, as has been happening, generally. But Covid-19 drugs and vaccines are just not for saving life, these are also intimately related directly to the livelihood of a very large global population, especially in the developing nations, like India. Therefore, ‘Coronavirus vaccine should be for everyone, not just those who can afford it,’ as articulated in the article, published in the STAT news on March 05, 2020.

This apprehension arises among many in the United States, as well. Mainly because, as reported in the above article, vaccine coming out of the two vaccine development projects funded by the U.S. government, one by Sanofi and another by Johnson & Johnson, may not be affordable to all Americans.

Further, quite a number of countries in the world lack resources, infrastructure, and health care personnel to detect the virus and prevent it from spreading quickly and easily among populations. In which case, without drugs and vaccines, the number of cases is likely to grow exponentially, putting stress on already burdened health care workers and facilities. Consequently, it will make harder to provide timely care for those who are ill. Thus, vaccines will be an important tool for preventing such a catastrophe.

For those with resources – ‘rich countries and rich people,’ a Covid-19 vaccine will certainly be valuable to save lives. However, for most people in all countries, including India, it may be essential for the livelihood, as well. Without it, they will suffer disproportionately and unnecessarily, the article concluded. Thus, in this hour of multiple crisis of global dimension, the drug players are expected to come forward, making these drugs and vaccines available, affordable and accessible to all, globally – a task where they can deliver the best, compared to others.

Conclusion:

Amid ‘Lockdown.4’ in India, as on May 24, 2020 morning, the recorded Coronavirus cases have mounted to 131,920 with 3,869 deaths. By the way, on the same day, the most populated country in the world – China, where Covid-19 struck first in December 2019, records 82,974 cases with 4634 deaths, so far.

That apart, Covid-19 is a very special situation for all countries, probably more than what happened during the 1918 Spanish flu pandemic, for several reasons. Comparing these two pandemics, especially during the lockdown period, has been common. Due to this pandemic, as many as 675,000 people, reportedly died only in America, many of them were previously healthy young adults. Almost similar situation is on the horizon with the Covid-19 pandemic.

Agreed, that the overall healthcare infrastructure and global scientific resources to combat these two pandemics may not be comparable. But even in the context of the 21st century, this is a very critical global situation, for both – saving life and also the livelihood. Thus, for pharma and biotech companies ‘this is not a time to make money’, as the chief executive officer of Serum Institute of India, which is helping produce a vaccine for Covid-19 developed by Oxford, puts it succinctly. Be that as it may, the answer to the two questions that I started with, still remains elusive.

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.

The Hype of Digitalization in Pharma Marketing

Having access to the fountain of knowledge residing in the cyberspace, fueled by word of mouth information and aided by social media, patients’ behavior is fast changing globally. Its degree may vary. But the change is real. The good news is – in a digital world of today, people are talking about ‘digitalization’ to rejuvenate per dollar productivity even in the pharma business, while navigating through a strong environmental headwind.

But, the bad news seems to be, that many pharma players, especially in India, can’t possibly quite fathom, just yet, the profound impact of the changing customer profile. With the hype of ‘digital marketing’ and associated cacophony, most of them seem to be focusing on automation of various processes with digital tools, rather than a customer-centric pan-organization digitalization of business. In this article, I shall dwell on the relevance of such intervention in the pharma marketing model, including the processes, before it’s too late for an organization.

The reality – profile of pharma consumers is changing:

It is well documented today that the profile of pharma consumers is changing. There are several studies in this area. For example, the McKenzie paper of November 2014, titled “A digital prescription for pharma companies,” penned some important observations in this regard, as follows:

  • Consumers in the healthcare sector are becoming more informed, empowered, and demanding.
  • The vast majority of connected patients using an array of digital tools, to take control of their health and the health care services they access and buy.
  • Over 70 percent of patients who are online in the United States use the Internet to find healthcare information, and around 40 percent of people who diagnosed their condition through online research had it confirmed by a physician.
  • Patients equip themselves with information about product safety, efficacy, cost comparison, quality indicators from websites and online communities.
  • The more healthcare data become digitally accessible, the more patients will use it to weigh—and potentially reject—expensive health care treatments, as is particularly true in the United States.
  • These patients are demanding more information, so they can apply the same cost-benefit analysis and research techniques they use to purchase cars or phones when they purchase health care.
  • They are also making more informed, rational choices about where they put their money.
  • If pharma companies do not join the digital dialogue and influence the conversation, they will lose an opportunity to shape it, and they may be put on the defensive trying to refute the statements made by those that do take part.

In this evolving scenario, the expectations of pharma customers even in India, are also changing. It may not be as fast as in the United States, but certainly can’t be ignored in any way, for long term business success. Thus, I reckon, it would be futile to keep the basic process of business as tradition-bound as it has always been, of course, with some interesting tweaking here or there.

When everybody talks about digital intervention, what it is really?

To effect this desired change, all concerned are now talking about ‘digitalization’. It has already become a buzz word and is often considered as a ‘magic wand’ by many enthusiasts. There is nothing wrong in this hype, provided this process is properly understood. I tried to explain it in my article, published in this Blog on January 2018. Are we missing wood for the tree? Let me start with the current ‘digitalization’ focus of pharma marketing in this area, particularly in India – as I see it.

Where’s the current focus on ‘digitalization’ in pharma marketing?

Generally, the pharma marketing focus broadly covers two different categories:

A. Push marketing 

B. Pull marketing

A. Push marketing: 

In my view, ‘push marketing’ involves targeting physicians through Medical Representatives and other means, including several contentious ones. These ensure that the doctors “push” the identified pharma brands of the company while writing prescriptions for patients. Some experts call it an ‘inside out’ and brand focused strategy of the industry players to drive sales.

Many companies are taking major digital steps to introduce automation in this area, which are not transformative, but incremental and aimed at improving productivity. Such drive encompasses many areas of a pharma organization, including the field staff related functions. For example, replacing usage of paper-based items, such as detailing folders or reporting material, with algorithm-based digital tablet devices. These reforms help answer customer questions promptly, besides almost real-time entry of accurate doctors’ call related data into a remote computer server for continuous analysis and feedback.

Automation of such types may free enough time of the field staff for greater customer contacts in different ways, but may not be considered as digitalization of the organization. Moreover, these are not transformative in nature either, as the overall process of doing business remains the same.

Nonetheless, process automation and its re-engineering add significant, but incremental value to the business, as the organization continues to maintain similar ‘inside-out’ focus on brands. The re-engineered processes also become faster and more accurate to help improve productivity. However, patients’ knowledge-base, needs, demands, values and aspiration keep changing fast, which just process automation can’t leverage to excel in business.

B. Pull marketing: 

Unlike ‘push marketing’, ‘pull marketing’ targeting pharma consumers who are increasingly becoming more informed and want to get involved in their treatment decision making process, including selection of a drug. The evolving trend suggests, to succeed in business, pharma players would require focusing more on patients, using various digital tools and platforms of engagement, in different ways.

To make this process meaningful, it is essential for a drug company to venture into mapping the patient’s journey from end-to-end for a specific disease or a set of diseases. This means capturing real-life data right from the time patients feel the need for a medical intervention, through the search for the right treatment, to effective disease management or cure, including follow-up, if any. Thus, mapping this arduous and complex odyssey would demand application of state-of-the-art digital tools.

Thereafter, equally sophisticated measures structured on digital platforms and formulated accordingly, require to be and implemented on the ground. It then becomes the ground-rock to transform the company’s focus – ‘through brands to patients’ to – ‘through patients to brands.’ Dovetailing this new marketing concept to a pan-organization initiative will call for new insight and wherewithal of the right kind.

When implemented by the right kind of people, this approach will encouragepatients to “pull” the demand of the selected brands, as they participate along with doctors in the drug selection part of the entire treatment process. The informed patients won’t hesitate posing questions to doctors – why ‘this’ drug is being prescribed and why not ‘that’ drug?’ The doctor would require responding with convincing answers in that situation. Some experts have termed this process as – an ‘outside in’ strategy.

Difference in impact – one ‘Incremental’, the other ‘transformative’:

It’s important to reiterate that the impact of digitalization for an ‘inside-out push strategy’, is generally incremental. Whereas, the same for ‘outside-in pull strategy’ is expected to be transformative in nature, not just in the business performance, but also the way pharma business is viewed and conducted as on date, especially in India.

Conclusion:

As I understand, process automation may be based on digital platforms and even with the application of Artificial Intelligence (AI) or robotics, the overall business process remains unchanged. It brings greater efficiency in the same business processes, improving employee productivity, and usually adds incremental success to brand performance.

Whereas, digitalization helps create a new way of achieving excellence – gaining a new insight for the business. This happens, first through generation, and then detail analysis of an enormous amount of relevant customer-centric data. Effective interpretation and use of the same, help transform the business – giving shape to new business processes for organizational distinction.

Simply speaking, automation improves the business efficiency with its key focus on ‘pushing brand prescription demand’, as much as possible. Whereas, digitalization aims at business transformation for a long-term organizational effectiveness. It creates a new purpose for business based on changing customer profile, across the organization. A sharp focus on delivering research-based and well-targeted customer values help ‘pulling brand prescription demand’, the decision of which is often jointly taken by the doctors and the patients or will happen that way even in India, sooner than later.

In this perspective, what we see in pharma marketing, generally in India, is automation of various types, of course, by using digital tools, platforms and even AI, in some cases. There isn’t anything wrong in that. But, digitization would call for much more. First, the core organizational focus to shift from being ‘brand-centric’ to ‘customer-centric’ for financial achievements, and then effectively delivering customer values through each ‘company-brand-customer interface’ and beyond that. This is essential for sustainable excellence of pharma players in the digital age.

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.

Drug, Patent and Hype: Quo Vadis Pharma Innovation?

A recent research report reveals, though the pharmaceutical companies in the United States since mid 2000 have spent over US$ 50 billion every year to discover new drugs, they have very rarely been able to invent something, which can be called significant improvement over already existing ones.

As per available reports, from the year 2000  to 2010, the US-FDA, on an average, approved just 24 new drugs per year. This number is a sharp decline from the same of 1990, when on an average 31 new drugs were approved per year.

These studies throw open some important questions to ponder:

  • What is then the real issue with pharma innovation? 
  • Is it declining quality or quantity (number)?
  • What impacts the patients more?

Quantity vs quality of innovation:

A recent paper explored whether declining numbers of New Molecular Entities (NMEs), approved in the United States (US) each year, is the best measure of pharmaceutical “innovation.”

Thus, studying in detail the NME approvals in the US during 1987 to 2011, the authors proposed the following three distinct subcategories of NMEs:

  • First-in-class
  • Advance-in-class
  • Addition-to-class

This classification was aimed at providing more nuanced and informative insights into underlying trends.

The paper established that trends in NME approvals were largely driven by ‘Addition-to-class’, or “Me too,” drug approvals. However, the good news is that ‘First-in-class’ approvals remained fairly steady over the study period.

Thus I reckon, there should be much greater focus with higher resource deployments for  more of ‘First-in-class’ drugs research and development.

To achieve this objective with requisite wherewithal, there will be a need to drastically cut down massive R&D expenditures on “Me-too” types of so called ‘innovative’ drugs. Such drugs, carrying exorbitant price tags,  creating a financial burden to the payers, could perhaps help increasing the number of innovations, but certainly not the quality of innovations to meet important unmet needs of patients in a cost effective manner.

Some facts: 

In 2010, the healthcare journal Prescire rated 97 new drugs or new indications. Only 4 of these provided any therapeutic advantage over the available existing drugs. Interestingly, 19 others (1 in 5) were approved despite having more harms than benefits.

According to another analysis, “About 1 in 6 new products had more harms than benefits, while more than half of all new products provided no advantages over existing options.”

Further, a different article published in Nature Reviews indicated, “doctors were more likely to rate drugs more than a decade old as transformative.”

Decline in the quality of innovation:

In this context, Dr Mark Olfson of Columbia University and statistician Steven Marcus of the University of Pennsylvania have reportedly established as follows:

“By the 1980s new drugs were less than four times better; by the 1990s, twice as good, and by the 2000s just 36 percent better than a placebo. Since older drugs were much superior to placebo and newer ones only slightly so, that means older drugs were generally more effective than newer ones.”

While even in earlier years, newer patented drugs on an average used to be 4.5 times more effective, as compared to placebo.

The winds of change?

As a result, under the new ‘Affordable Care Act’ of President Obama, “comparative effectiveness research” by an independent research institute could well conclude that older drugs or even cheaper generic equivalents are better than the high priced patented ones, which create fortunes for the innovator pharmaceutical companies at the cost of patients and payers.    

The above initiate in ‘Obamacare’, if and when fructifies, will indeed hit the ‘Me-too’ type of drug innovators, especially in the United States, very hard. Nevertheless, is a music to the ear for the private health insurance companies and the patients at large.

A ray of hope?

‘Comparative drug effectiveness analysis’, as stated above, could eventually lead to replacement of newer high priced ‘me-too’ patented drugs by older relatively low priced generic equivalents, at least, for reimbursements.

This will, no doubt, lead to huge profit erosion of the big pharmaceutical players. Hence, extensive lobbying by industry groups in top gear, against this ‘patient-centric’ proposal, is currently on, .

As the new federal healthcare law will find its roots in America, despite strong opposition  from the powerful and influential pharma lobby groups, a ray of hope is now  faintly seen in otherwise blatantly exploitative and rather cruel drug pricing environment.

Where hype is the key driver:

Despite enormous hype, being created and spearheaded by the Big pharma, on the ‘essentiality’ of most stringent Intellectual Property Rights (IPR) regime in a country with patent laws blatantly in favor of commercial considerations, to enjoy a monopolistic marketing climate with pricing freedom, breakthrough pharma innovations are now indeed rather difficult to come by, as we shall deliberate below.

Reasons for decline:

Many experts believe that the following reasons, among many others, have attributed to the decline in the quality of pharmaceutical R&D output:

  • Most important drug discoveries for mankind have already been made or in other words, the low hanging fruits of pharma R&D have already been plucked. Now not so easy and rather difficult drug targets are remaining.
  • In the last decade, most of pharma R&D efforts were reportedly concentrated mainly in four major disease areas: central nervous system, cancer, cardiovascular and infectious diseases.
  • There is a need now to focus more on poorly understood and more complex therapeutic areas such as, autoimmune diseases or complex diseases related  immune system of the body, to meet greater unmet needs of patients.
  • Clinical trial volunteers are now more difficult to recruit and treat.
  • More stringent regulatory requirements for clinical trials with studies using much larger number of patients, making the clinical drug development process very expensive.

Could it be worse for Big Pharma?

The evolving situation, though very early in the day now, has the potential to turn much worse for the big pharma and good for the patients, if some key changes take place.

Many industry analysts, across the world, feel that ‘liberal’ patent laws are responsible for acceptance of minor advances over the existing products as patentable with 20 years of market exclusivity.

Thereafter, another ‘liberal’ minded drug regulatory framework allows the pharma players to market such ‘not-so-innovative patented medicines’ aggressively, enabling them to amass astronomical profits in no time at the cost of patients’ interests and payors’ financial burden , as happened in the United States and many other countries recently.

To avoid such trivial innovations the law and policy makers in the industrialized countries may well ponder as follows:

1. Align the country’s ‘Patents Act’ with similar to what Indian law makers had formulated in 2005 to avoid minor and ‘evergreening’ types of patents under section 3(d) of the Act.

2. The clinical research data must establish that the new drugs offer significantly more tangible benefits to the patients than the existing ones.

Denial of patentability for ‘me-too’ innovations and their subsequent regulatory approvals would significantly reduce the drug treatment cost with virtually no adverse impacts on patients, across the world.

If such measures are taken by the developed countries of the world and also the emerging markets, the Big Pharma would be compelled to change their respective business models, making ailing patients of varying financial status, color and creed central to their respective strategic ideation processes.

Otherwise, it is highly unlikely that anything will change for the patients from what we are all experiencing today, at least in the near to medium term.

A possible pathway:

Highly conflicting interests of Big pharma and the patients, should get resolved sooner than later and that again for the interest of both. 

Thus, to find a meaningful and generally acceptable solution to this issue, there is a dire need for a much wider global debate. The deliberations, at the same time, should include possibilities of finding ways to avoid huge wasteful expenditures on pharmaceutical R&D for developing new products that offer no significant benefits to the patients over the existing ones. On the contrary, such products burden them with exorbitant incremental drug treatment costs, 

The motions of the debate could well be in the following lines:

1.  ‘Should United States amend its patent laws by categorically stating that a mere “discovery” of a “new form” of a “known substance” that does not have properties resulting in significant improvement in clinical efficacy, will not be patentable?

2. Shouldn’t the clinical research data must always establish that the new drugs offer significantly more tangible benefits to the patients than already available cheaper equivalents?

The positive outcome of this global debate, if fructifies, will indeed be considered as a paradigm shift in the new world order for all, hopefully.

Unfathomable reluctance: 

Despite all these developments, a recent report indicated that the heads of seventeen industry associations of the United States wrote a letter to President Obama complaining, among others, India’s patents regime. This includes the most powerful, yet equally controversial, pharmaceutical lobby group of America.

The letter alleged that the recent policy decisions in India undermine internationally recognized Intellectual Property (IP) standards, which are “jeopardizing domestic jobs” in America and are unacceptable to them.

Though the details of issues were not highlighted in the letter, One concern it specifically expressed that the defeat of Novartis on the Glivec case that challenged Section 3(d) of the Patents Act of India has raised the bar on what can be considered a true innovation for the grant of patent in India.

Though this judgment of the apex court of India was widely acclaimed even globally, American Trade Association Lobby Groups seem to project exactly the opposite, reportedly, driven solely by profit motives of their members and shorn of patients’ interests

Interestingly, an article published in The New England Journal of Medicine, July 17, 2013 also states as follows:

“A patent law that treats incremental innovation and significant innovation in the same way, encourages companies to prioritize less important research over more important research.”

A diametrically opposite viewpoint:

Another school of thought leaders opine, ‘me too’ innovations will continue to remain alive and well. This will happen, even if such new products are starved of oxygen by ‘the tightening purse strings of the eventual customers’. These innovations are sustained by the stronger imperative to avoid clinical failures and to play relatively safe in the space of expensive R&D investments.

They feel that pharma players will continue to focus on to leaner drug discovery and development models to have healthier late-stage product pipelines of such types.  In tandem, by cutting costs even more aggressively, as we witness today, they will find space to keep the level of risk optimal for delivering real innovation, when the time comes.

This type of business model, the experts feel is based on the belief that it is far better to acquire a product with very little innovation ensuring that it can hardly fail to be approved by the regulator. Thereafter, the concerned players may figure out ways of how payors will actually pay for it, rather than focusing primarily on acquiring a genuinely innovative ‘First-in-class’ product and then discover it has ‘feet of clay’.

For example, AstraZeneca reportedly invested a little over US$1 billion in two such products in one month: another LABA combination from Pearl Therapeutics and a prescription ‘Fish Oil’ capsule from Omthera Pharmaceuticals.

Conclusion:

Be that as it may, a large number of experts do opine, especially in the light of the above letter of the American Trade Associations that the verdict of the Honorable Supreme Court of India on the Glivec case, though does not serve the business interests of pharma MNCs, definitely signals the triumph of justice over ruthless patient exploitations. It also vindicates that this particular rule of law, as enacted by the Indian Parliament, is indeed for the best interest of the patients of India at large.

This verdict could well be construed as a huge lesson to learn and implement by other like minded countries, across the world.

Having a glimpse at the pharmaceutical innovations, which are often laced by crafty hypes created by expensive PR Agencies of the pharma lobby groups, the global thought leaders do tend to believe, rather strongly, that Section 3(d) of the Patents Act of India would encourage more ‘First-in-class’ innovations, in the long run, benefiting all.

Such a provision, if implemented by many countries, could also help saving significant wasteful expenditures towards ‘Me-too’ type pharma R&D, favorably impacting billions of lives, across the world.

That said, the question keeps haunting – ‘Sans Hype, Quo Vadis Pharma Innovation?

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.

 

 

 

Hype on “Superbug” – national pride – rational mind

Since around last fortnight Indian media of all types and forms, have been fiercely competing with each other to attract the ‘eye balls’ of the viewer/readers through ‘alarming’ news items starting from the situation in the J&K to the ‘rampant corruption’ involving the Commonwealth Games, with of course their usual (over)dose of sensationalism.

In a situation like this to prove ‘enough is JUST NOT enough’, as it were, on August 11, 2010, the well-known medical journal of repute “The Lancet” published a routine article, which further added to the ‘media sensationalism’ in India. The report highlighted that a new ALL antibiotics-resistant “Superbug” originating from Pakistan, appears to have taken its first life. This happened when a patient who was brought to a hospital in Belgium and died in June this year after having met with a car accident in Pakistan, where the diseased was infected by this ‘Superbug”.

This article in ‘The Lancet’ written by a team of international researchers including an Indian, elaborated that a new variety of enzyme named after India’s national capital New Delhi, called, “New Delhi Metallo beta lactamase” in short “NDM 1” turns any bacteria into a deadly “Superbug”, making it resistant to ALL types of antibiotics, leaving virtually no cure in sight.

It was also reported that this deadly “Superbug” has already reached the United Kingdom through patients who acquired it from the hospitals in India. The article reported that the deadly “Superbug” originated from the hospitals of Pakistan and India has the potential to precipitate serious health issues across the world.

“The New Delhi Superbug” was discovered even earlier:

This report generated a sharp reaction in India and from some of its authors regarding its authenticity. Some experts even termed this study as the ‘Western plot to undermine medical tourism in India’.

A leading daily of India reported, “Indian medical journal first documented Superbug”. It stated that that the first ever formal documentation of this ‘Superbug’ was made last year at the P.D. Hinduja National Hospital and Medical Research Centre located in Mumbai. This finding was published in the ‘Journal of the Association of Physicians in India (JAPI’) in March 2010. The reason for the emergence of the ‘Superbug’ was attributed to the ‘worrisome outcome of the indiscriminate use of antibiotics’.

“Unfair to blame the country for the ‘New Delhi’ superbug”:

Reacting to this article, Indian health authorities opined, “It is unfortunate that this new bug, which is an environmental thing, has been attached to a particular country.” The reasons being, “Several superbugs are surviving in nature and they have been reported from countries like Greece, Israel, the U.S., Britain, Brazil and there is no public health threat and no need to unnecessarily sensationalize it”. Some experts, however, feel, “such drug resistant bacteria is a matter of chance, is a global phenomenon and is preventable by sound infection prevention strategies which are followed in any good hospital.”

It has been reported that the ‘National Center for Disease Control of India’ is working on guidelines for appropriately recording these types of nosocomial (hospital acquired) infections.

“Superbug” Hype and Medical Tourism:
Many people of both India and Pakistan have felt since then that in absence of an effective response by the health authorities, especially, in India the fast evolving Medical Tourism initiatives, providing medical services ranging from complicated cardiovascular, orthopedic and cerebrovascular surgery to other life-threatening illnesses, may get adversely impacted.

The root cause and the ‘blame game’:

Experts have opined that overuse and imprudent or irrational use of antibiotics without any surveillance protocol are the root cause for emergence of such ‘Superbugs”, though some Indian parliamentarians have termed this article as the propaganda by some vested interests. It has been alleged that the study was funded by the Wellcome Trust and Wyeth, the two global pharmaceutical companies who produce antibiotics to treat such conditions, together with the European Union.

In this context it is worth mentioning that ‘The Lancet’ article in its disclosures says:

“Kartikeyan K Kumarasamy has received a travel grant from Wyeth… David M Livermore has received conference support from numerous pharmaceutical companies, and also holds shares in AstraZeneca, Merck, Pfizer, Dechra, and GlaxoSmithKline, and, as Enduring Attorney, manages further holdings in GlaxoSmithKline and Eco Animal Health. All other authors declare that they have no conflicts of interest.”

Such a situation has not been reported for the first time:

This type of situation has indeed some precedents. When ‘MRSA’ was reported for the first time, it caused similar scare. However, this time many experts feel that it is too early to conclude whether or not ‘NDM-1’ will eventually prove to be more dangerous than ‘MRSA’.

Several such “Superbugs”, as stated earlier, have already been reported from countries like Greece, Israel, USA, UK, and Brazil. However, as I know, in the battle against infectious diseases involving both the scientists and the bacteria, the later had always to succumb, in the long run.

‘NDM-1′, as well, perhaps will be no exception. All concerned MUST continue to make it happen, not by mere wishful thinking but by establishing a strong procedural mechanism to keep a careful vigil on the reasons for emergence of drug resistant bacterial strains in the country.

The World Health Organization (WHO) perspective:

On Saturday, August 21, 2010 the WHO commented, “while multi-drug resistant bacteria are not new and will continue to appear, this development requires monitoring and further study to understand the extent and modes of transmission, and to define the most effective measures for control”.
Conclusion:

The hype created and motives attributed by the media and the politicians over one such routine scientific papers published in a medical journal of international repute, in my view are unwarranted. There are built in systems within the scientific discourse for raising questions and even challenge any findings. Remarks made by one of the authors of the article to the media, perhaps added more fuel to the fire. Politicians seem to have joined the bandwagon to politicize even a benign medical issue captured in the said article. In an era where news items mean “sensationalism” and ‘politicization’ of most such news items is the order of the day, the civil society should be helped to understand the core issues behind all such raging debates.

Besides the reasons, as discussed earlier, attributed to repeated emergence of such “Superbugs”, one more issue I could foresee in today’s environment compared to the same in the past. This issue possibly lies in the shift in focus of pharmaceutical R&D from discovery of novel drugs for infectious diseases to discovery of drugs for non-infectious chronic illnesses like, metabolic disorders (diabetes), hypertension, cardiovascular diseases, psychiatric disorders, cancer, vaccines etc. This shift in the R&D focus has obviously been prompted by the tilt in the prevalence of the disease pattern towards the same direction.

Perhaps for this reason, one notices hardly any significant and novel molecules in the research pipelines of either global or local pharmaceutical companies to treat such antibiotic-resistant infections. It is understandebly not an ‘either/or’ situation. However, as we all know, in life-threatening conditions both types of drugs have their respective places to save precious lives. Let us ponder over it.

By Tapan 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.