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Regulatory Failures Are Still Risking Patient Lives

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India’s pharmaceutical industry faces renewed scrutiny as the Drug Controller General of India (DCGI) flagged numerous substandard drugs in September 2024. At the same time, an October 02, 2024, Business Standard report highlights an ongoing crackdown on such drugs by regulators. This article explores these contrasting developments, beginning with the September findings.

On September 22, 2024, multiple reports revealed that the DCGI, through the Central Drugs Standard Control Organization (CDSCO), identified 195 instances of substandard drugs, devices, and vaccines over three months. Popular brands like Shelcal 500, NICIP MR, and Pantocid were among the flagged drugs, affecting treatments for common ailments like hypertension and acid reflux. Major companies like Alkem, Sun Pharma, and Hetero Labs were implicated. The DCGI ordered the withdrawal of these drugs and called for stricter vigilance, highlighting ongoing issues despite regulatory frameworks being in place, which is known to all drug manufacturers, but still happening all over the county.

Industry Response: 

After the DCGI’s September 2024 report on substandard drugs, responses from pharmaceutical companies were mixed. Many large firms cooperated, taking corrective steps to comply with Good Manufacturing Practices (GMP) and tightening quality control. Some acknowledged the need for stricter oversight and preventive measures.

As happens mostly, there has been notable pushback from a portion of the industry, particularly smaller and mid-sized manufacturers. These companies argue that the stringent audits and frequent shutdowns due to non-compliance are creating significant financial and operational pressures.

Interestingly, some large manufacturers claimed that the faulty products were counterfeit or spurious. This makes the scenario even more complex. Although, both endanger patient lives.

Decades of regulatory failures persist, but at what cost? 

Back in June 2015, I highlighted that “Fake Drugs Kill More People Each Year Than Terrorism Over the Last 40 Years.” Shockingly, little has improved since then.

The problem is deeply rooted in nations with weak enforcement - India being a prime example. Alarmingly, the Ministry of Health has long downplayed this threat, as it appears now.

For example, even prior to that, in 2009, their “Report on Countrywide Survey for Spurious Drugs” grossly underestimated the issue, claiming only 0.046% of spurious and 0.1% substandard branded drugs. This underreporting reflects a dangerous “Ostrich Syndrome” among regulators, who continue ignoring this life-threatening crisis, leaving millions at risk.

The question I raised in this blog on October 12, 2015 2015 still haunts me today: “Does India produce ‘world-class’ medicines for all?” Effective checks and accountability are crucial to address this crisis.

To tackle counterfeit drugs, India needs a comprehensive strategy, such as:

  1. Strengthen Regulation: Stricter inspections, penalties, and GMP adherence.
  2. Leverage Technology: Implement digital tracking systems.
  3. Improve Coordination: Better agency collaboration and audits.
  4. Foster Industry Self-Regulation: Internal audits and regulatory partnerships.
  5. Raise Public Awareness: Educate consumers, protect whistleblowers.
  6. Adopt Global Standards: Align with international benchmarks.

Only with strong accountability can India safeguard drug safety.

While there have been reports of some progress, concerns remain:  

A Business Standard report from October 02, 2024, highlights a regulatory crackdown on substandard drugs. However, this raises critical questions about the true effectiveness of these efforts. Upon closer inspection, the report reveals limitations that warrant deeper scrutiny. These include gaps in data coverage, inconsistent inspections, and doubts about the sustainability of the actions taken, which cast doubt on how far-reaching and impactful this so-called crackdown really is.

Some of the notable flaws that I find in the report include:

  1. Lack of Comprehensive Data: The report focuses on inspected units, which represents only a small fraction of India’s vast pharmaceutical manufacturing sector, especially considering that 80% of India’s pharma units are micro, small, and medium enterprises that often escape the regulatory radar.
  2. Limited sample size could misrepresent the true scale of substandard drug production.
  3. Inconsistent Inspection Coverage: While the CDSCO has ramped up its audits, the inspection coverage appears uneven. Many smaller manufacturers, particularly those operating in less regulated states, may not face the same scrutiny as larger companies. This could skew the perception of improvement.
  4. Global Discrepancies: Despite claims of reduced international complaints, the report doesn’t fully address concerns like the recent ban on Indian-made antibiotics by Nepal, signaling that quality issues persist in exports.. This suggests a gap between domestic inspections and international quality standards. 
  5. Sustainability Questioned: The report emphasizes short-term regulatory actions, but long-term sustainability is unclear. Temporary shutdowns and corrective actions might not be enough to ensure lasting quality improvements, especially in an industry facing systemic issues like weak documentation and quality control in smaller firms 

In summary, while the report provides some optimistic updates, its credibility is limited by incomplete data, uneven enforcement, and questions about long-term impact. 

Is entity-centric accountability grossly missing in this area? 

Absolutely. The accountability of both regulators and pharmaceutical companies regarding substandard and counterfeit drugs in India has been alarmingly deficient for years. Despite recurring reports of poor drug quality, weak enforcement, and ineffective oversight persist. 

Regulatory bodies have failed to consistently hold companies accountable, allowing dangerous drugs to flood the market and endanger public health. This systemic neglect, coupled with inconsistent audits and lax penalties, has led to a crisis that remains unresolved even today. Thus, the following two areas, I reckon, need to attract greater focus:

  • Regulatory Gaps: The Central Drugs Standard Control Organization (CDSCO) has faced criticism for being reactive rather than proactive, with irregular inspections and delays in addressing violations. The weak enforcement of Good Manufacturing Practices (GMP) and insufficient penalties for violators have allowed substandard drugs to continue circulating.  
  • Pharma Companies’ Compliance: Many pharmaceutical companies have either ignored or downplayed the issue, sometimes blaming counterfeiters rather than addressing quality control lapses. While larger companies might cooperate after being caught, the lack of strict and consistent regulatory pressure has allowed many manufacturers to evade full accountability.

This lax accountability, both in the regulatory framework and among drug companies, has created an environment where the production and distribution of substandard and fake drugs continue to pose serious risks to public health in India. The need for stricter enforcement and transparent accountability is crucial for restoring trust in the system.

Conclusion:

Despite years of scrutiny, regulatory lapses in India’s drug industry continue to jeopardize patient safety. Weak oversight and inconsistent enforcement allow substandard and counterfeit drugs to flood the market, with deadly consequences.  

Regulatory bodies have failed to take firm action, and pharmaceutical companies are often not held accountable. As a result, millions remain at risk, and trust in the healthcare system is eroding. The cost of these failures is measured in lives, and without immediate reforms, the crisis will only deepen.

This underscores the point that the time for complacency has passed – India’s healthcare system and public trust demand swift, decisive action against counterfeit and low-quality drugs, with clear accountability and stringent punitive measures for violators.

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.

 

Leveraging Data Science To Deliver Unique Patient-experience

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“Changes in consumer behavior, many of which were accelerated by the COVID-19 pandemic, are fueling a redesign of the health ecosystem.” This finding was revealed by a recent study of the PwC’s Health Research Institute (HRI). The research provided insights about how and why specific groups of consumers used health services during the pandemic – from mental health and telehealth to in-home care and other non-traditional care sites.

The study also captured ‘their willingness to use them again in the future,’ and suggested, those pharma companies that closely monitor these consumer signals and design, accordingly, will likely emerge as more customer centric, as the pandemic wanes.

From this perspective, effective application of data science for creating a unique patient experience by listening to patient voice, is now an imperative for pharma players. Which is why, this approach is nowa key business success ingredient in the changing paradigm. It helps offering a holistic disease treatment solution to patients searching for an effective and affordable disease treatment process.

This article will, therefore, focus on leveraging data science for strategic use of Real-World Evidence (RWE) based on Real World Data (RWD) – on how customer characteristics and behavior impact health outcomes. This initiative is fast becoming a key driver to excel in contemporary pharma business.

Strategic use of RWD/RWE increasing in pharma marketing plans:

RWE, as the name suggests, is the evidence derived from RWD. These are collected outside of clinical trials from various sources, such as, patients and HCP surveys on treatment outcomes, electronic health records wherever available, Wearable Health Devices (WHD), insurance claims, data from connected healthcare records, custom study and many others.

The McKinsey & Company article in this area, published on July 23, 2020, also indicated so. Although, some leading pharma companies have already been using RWE. However, recent progress in digital and advanced analytics allows it to be employed in new ways to deliver impact at scale, the article highlighted. When used by hands-on- professionals of repute in this area, RWE can help pharma marketers understand how patient characteristics and behaviors affect health outcomes.

The research paper on how Biopharmaceutical companies are embedding real-world data and evidence use across the enterprise, published in Deloitte Insights on September 21, 2022, presented an interesting contemporary example. It wrote: ‘During the COVID-19 pandemic, RWD/E played a key role in enabling Biopharma companies to innovate and bring novel vaccines and therapies against this highly contagious disease to market in record time.’id-19,

The approach gained momentum during the Covid-19 pandemic:

The above research study of Deloitte brought out this fact succinctly. It found; unprecedented challenge posed by COVID-19 pandemic prompted several drug companies to leverage RWD/E to innovate faster than ever before. More than half of the companies surveyed by Deloitte used RWD/E to understand the incidence and severity of COVID-19 and its variants for vaccine and drug development.’

The survey found: ‘Many vaccine developers, such as Johnson & Johnson analyzed RWD to predict COVID-19 hotspots across geographies to optimize site selection and collect data from diverse racial and ethnic groups.’ Besides, RWE also played a critical role for these companies in understanding vaccine effectiveness across demographics such as age, gender, race, and ethnicity and determining the need for boosters.

Improves patient experience for business excellence:

A systematic and ongoing tracking and analysis of well-identified RWD, by pharma marketing analytics professionals, can help in-depth understanding of changing pharma customer characteristics and behavior, more precisely. Such initiatives include patients, HCPs, hospitals and even the policy makers. Several drug majors have adopted this practice, immediately after absorbing the initial shock of unprecedented disruptions during the Covid-19 pandemic.

Similarly, RWD can help map the exact available space for demand where a brand is being used and potential competitive value-space for its further demand extension – based on real time customer behavior with changing characteristics. To shape customer journeys, such findings may immensely help while strategizing for more targeted content delivery, with sharper segmentation and brand positioning.

Therefore, finding such gaps in various areas of patients’ journey – in their search for an effective and affordable treatment, and appropriately filling these up with brand value delivery is critical. This will help improve patient experience manifold, accelerating business excellence, in tandem.

A recent paper titled, ‘Maximizing your role as a newly appointed real-world evidence leader,’ published by the ZS on March 23, 2022, made similar observations, as above. The study reiterated that patient-generated insights obtained through RWE, are uniquely capable of adding value at different stages of a pharma brand’s life cycle. Or, throughout a patient’s journey on the care pathway of the value delivery system. It concluded: “Carrying out a successful RWE study is a fine balancing act – but its inconveniences and risks are almost certain to be outweighed by the eventual benefits.”

Increasingly used to gain actionable insights to improve patient experience:

In the contemporary market dynamics – driven by changing customer characteristics and behavior, several pharma companies are now effectively combining and analyzing RWD to retrieve RWE. The objective is to gain actionable insights for effective customer engagement for better patient outcomes, to drive business growth. According to a recent podcast by PwC on using data to shape customer journey, the process includes the following:

  • Focusing on the value and outcomes of treatment protocols and less about specific products.
  • Gaining a better understanding of pharma customers and what drives their behavior.
  • Reaching beyond the barrier in driving differentiation amongst competitors.

Conclusion:   

The Forbes article on the Data Science trend in 2022, published on October 04, 2021, aptly epitomized its relevance in today’s business, including pharma industry. It articulated, data science encompasses the practical application of ideas generated by credible and meaningful data from various relevant sources, predictive analytics, and artificial intelligence. Our ability to use such data to our advantage across wide areas in business, would help deliver increasingly worthwhile, valuable, and enjoyable patient experience. 

The article also underscored: ‘If data is the oil of the information age and Machine Learning (ML) is the engine, then data science is the digital domain’s equivalent of the laws of physics that cause combustion to occur and pistons to move.’

Thus, I reckon, both intrinsic and extrinsic brand value creation process, driven by its effectiveness, would increasingly call for Real World Evidence (RWE) based on top-quality Real-World Data (RWD). This is increasingly becoming so critical for success – spanning right across, from product development, launch planning with value propositions – to launch and beyond.

The core purpose of leveraging data science in pharma is, as I see it, is effective decision making throughout the brand life cycle, to deliver a unique patient experience in patients’ journey – with better treatment outcomes.

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.

What Have And Haven’t Changed In Pharma’s New Normal?

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While navigating through the challenge of disruptive changes, several pharma marketers are now focusing more on creating, connecting, and leveraging all market and customer related data, across the organization. Astute ones are using state-of-the-art tools, platforms, and techniques to gain actionable insights on new demands of pharma markets. I wrote about it in my article - ‘Data: the new ‘Magic Wand’ For Pharma Business Excellence,’ published in this blog on October 01, 2018.

This process is helping them to fathom what areas the pandemic has changed and what it hasn’t. Their aim is to draw cutting-edge strategies accordingly for market effectiveness – outperforming competition. This article will explore that space with contemporary examples. Let me start with a few illustrations of some hits and misses for the treatment of Covid – as the world started learning to live with this menacing virus. This was enviable, as the requisite scientific date wasn’t readily available at that moment of truth. But the time has changed now.

Some hits and misses:

As the pandemic overwhelmed the world, and no well-documented treatment for infection caused by the brand new virus – Covid-19 was available, many drug players were given quick emergency approval by country regulators for some repurposed drugs. But most of those weren’t found effective as fresh clinical data started pouring in. For example, the World Health Organization (WHO), have, reportedly, indicated that remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon regimens appeared to have little or no effect on 28-day mortality or the in-hospital course of COVID-19 among hospitalized patients.

More recently, Gilead Sciences Veklury – a failed Ebola drug, repurposed for hospitalized Covid-19 patients, suddenly became a blockbuster drug, according to a September 17, 2021 report. However, in less than a year, alongside more research data - a study from Europe, published in The Lancet Infectious Diseases, showed that Veklury has no real benefit. The report also highlights: ‘Aided by a ringing endorsement from then-president Donald Trump, Veklury rang up sales of $2.8 billion in 2020, including $1.9 billion in the final quarter. But those sales slid this year to $1.5 billion in the first quarter followed by $829 million in the second quarter.’

Similarly, there are several areas that are seemingly getting transformed, triggered by the pandemic and the time for resorting to a hit or miss approach, is now virtually over. From pharma marketers’ point of interest, it will now be at one’s own peril for not challenging the pre-Covid business traditions, rules, and well-tried strategies on customer relationships and brand building models. This brings us to the question on what specifically have changed in the new normal as the pharma industry navigates thorough the Covid pandemic – for close to two years now.  

Pandemic-triggered changes in the pharma marketing area:

Changes are many and are being studied across the world. One such recent analysis, articulating how the pandemic triggered changes have redefined marketing, was published by the Harvard Business Review (HBR), on March 10, 2021. This paper came more than a year after the pandemic overwhelmed the world. This article listed some interesting macro-level changes, including the following:

  • Old normal: You are competing with your competitors.
  • New normal: You are competing with the last best experience your customer had.
  • Old normal: Customers hope you have what they want.
  • New normall: Customers expect you to have exactly what they want.
  • Old normal: Courting customers is just like dating.
  • New normal: Courting customers is just like online dating.
  • Old normal: Customers must sit at the heart of your marketing strategy.
  • New normal: Customers must sit at the heart of your customer journey.
  • Old normal: Agility is a technology process.
  • New normal: Agility is a modern marketing approach.
  • Old normal: Your brand should stand behind great products.
  • New normal: Your brand should stand behind great values.

To illustrate the point, let me now give a few examples of some micro-level changes in the same space.

Some transformation trends:

I am citing a few examples related to pharma’s traditional sales and marketing models. One such area is, quite a few companies are adopting connected data based and analytics-supported Omnichannel approach for customer engagement. The key objective is to deliver coherent and high-quality customer experience.

The need for new commercial models for the changing life sciences market, was also highlighted in an interesting article, published in the Pharmaceutical Executive on September 16, 2021. The authors identified six health care macro trends, demonstrating the value of transforming care delivery and shifting market behavior that prompt to reframe customer value propositions.

Taking a cue from this paper, I am listing below some of the current trends – as I see these and wrote before in this blog. Each one of these calls for well-connected data with analytics support:

  • Fostering a new genre of ‘customer-brand relationship’ to drive more targeted go‑to‑market strategies, enhanced agility/mobility of resources and highly personalized customer interactions.
  • Meeting the growing demand for value‑based care with novel risk‑adjusted and outcome‑based Price-Value-Models, supported by ongoing innovation in this area and sophisticated approach to value, affordability and outcomes.

Interestingly, despite Herculean constraints, many pharma players continued creating and delivering value, as the customers were expecting with changing situations.  

Drug-price sensitivity is increasing:

In the new normal, drug price sensitivity of customers is increasing manifold, for various reasons. A June 18, 2020 study, flags: ‘Nine in 10 Concerned About Rising Drug Costs Due to COVID-19.’ Although, this particular study (Gallup Poll) was conducted in the United States, general public apprehension is no different in other parts of the world, including India.

In my article of September 14, 2020, I also wrote that the concept of ‘fair pricing a drug’ is being deliberated by many experts around the world, since quite some time, till today. But it continues. Most recently, as reported on September 22, 2021, for different reasons related to its new Alzheimer’s drug - Aduhelm, including its hefty price tag of $56,000 annually per patient, ‘Biogen reps banned from D.C.-area neurology clinics.’

Regardless of such customer reactions, the pharma industry, as reported on September 17, 2021, continues to advocate – drug pricing pressure will stifle innovation, blocking patient access to needed medicines and dry up investment in important R&D on new therapies. Curiously, the Pharmaceutical Research and Manufacturers of America (PhRMA), is spending more than $1 million on TV ads as part of a massive lobbying and communications campaign emphasizing the potential harm to patients seeking cures for deadly diseases, as the report highlights.

Innovation – remained mostly unhindered from old to new normal:

Customers’ expectations can’t be ignored indefinitely. Interestingly, the world has also witnessed it with Covid drug and vaccine innovation continuing even during the most trying times during the pandemic, even in India. It is, therefore, quite understandable why unfettered access to drug innovation is considered an oxymoron, by many.

The good news is, despite shrill voices over pricing measures, the quest for adding meaningful value to the healthcare space continues unhindered. As reported on September 19, 2021, both Pfizer and Merck are advancing oral antiviral candidates targeting Covid-19 into late-stage testing. Thus, I reckon, regardless of jarring noise from pharma lobbyists, drug innovation, willy-nilly, has to satisfy the diverse demand of health care customers.

Innovation needs to satisfy demands of diverse healthcare customers:

That, increasingly, drug innovations will need to be based on their ability to satisfy the demands of life sciences companies’ diverse customer-perceived value-based, was also echoed by the Pharmaceutical Executive article of September 16, 2021.

While doing so, companies will need to structure innovation in terms of health outcomes, affordability, and personalization, as the paper emphasized. It further added, ‘broader definition of innovation means products are no longer the central driver of value.’ Instead, innovation will be powered by an increasingly diverse stream of data that resides outside the confines of the traditional health ecosystem.

Covid pandemic accelerated the transition of this process of innovation, drawing its new focus on providing a seamless and holistic customer experience in the disease treatment process – supported by advanced analytics and this deeper understanding of customer segments.

Conclusion:

Many pharma marketers have possibly undertaken a sophisticated and credible market scanning exercise in the new normal, to assess by themselves what have or haven’t changed in their customer preferences and market dynamics. If not, I would encourage them to initiate it, at least, now.

Equally noteworthy, as the above HBR article wrote, in the post pandemic period: ‘Beyond geography, marketing messages need to be personally relevant, aligned to an individual’s situation and values, as opposed to demographics, such as age and gender.’

The objective is to create a personal connection between the customer and the brand promotional content, aiming to influence the prescribing and purchasing behavior, based on their psychographic to attitudinal characteristics. This process would require creating and screening lots of customized data, supported by sophisticated analytics.

From the above perspective, I reckon, deep insight on what have or haven’t changed in the healthcare environment alongside its customers, would be of fundamental importance for pharma marketers, in the new normal.

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.

Pharma’s Digital Initiatives In India: A Missing Link

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An interesting study – designed to investigate the challenges that Health and Human Services (HHS) organizations face in implementing digital and data solutions, stands out today – for many reasons. One such being, this ‘multi-country survey’ project team had no inkling about the pandemic when the project was undertaken.

This study was conducted by a research team from Imperial College London’s Institute of Global Health Innovation (IGHI), and was sponsored by EY. The survey comprises of more than 2,000 global HHS professionals – from India, Australia, Italy, UAE, the UK and the US. 359 respondents were from India.

The research passed through the phase when Covid related disruptions was about to put HHS providers through the most extreme stress test in living memory. ‘While the outbreak was catastrophic in its effects, it presented the researchers with an exceptional opportunity to study the sector’s behavior during a pivotal moment,’ the paper noted.

From this perspective, today’s article will explore, from various different sources, across the world, how Covid-triggered rapid development and adoption of digital solutions are in the process of making a paradigm shift in the healthcare space. It spans across – health care service providers, its users, and practitioners – including pharma industry and the tech-solution developers.

Consequently, the question arises, would healthcare industry’s innovative spirit of 2020 is robust enough for taking a quantum leap in this space, as we move on. That space will span across – conceptualization and development of new health care products and services, alongside their consumption pattern and consumer behavioral dynamics. And, right up to the adoption of cutting-edge digital technology for commensurate delivery mechanisms. Let me start with some key findings in this area from the above report.

Some key findings – Global and India:

The findings of the Report titled, ‘Embracing digital: is COVID-19 the catalyst for lasting change?’ published on January 13, 2021, ferreted out some interesting facts, with details. These encompass both global and Indian scenario, in this area.

Some key findings – Global:

  • Pre-pandemic – just 18% of HHS providers had managed to embed digital tools in the way they work – mostly, due to lack of funds, regulatory restrictions, and risk aversion. However, the pandemic outbreak swept away many of these barriers, as 62% of organizations have now started using digital technologies and data solutions, globally.
  • 48% organizations are planning to continue investing in technology during the next three years, with 33% expecting more than 50%, and 19% more than 100% increase in investment.
  • While phone consultations are being offered by 81 % of HHS organizations (up from 39 % before the pandemic), 71 % of organizations offering video consultations (up from 22 % before the pandemic).
  • Respondents’ top objectives for future investment towards rapid adoption of digital solutionsinclude, transforming ways of working and service delivery, improving quality of care, reducing the administrative load, enabling better communications, and streamlining work processes.
  • However, 47% of respondents think, the introduction of digital and data solutions was a temporary measure to address challenges during the pandemic.

Some key findings – India:

The Covid-19 pandemic triggered fast acceleration of the adoption of digital technologies by the HHS in India, as well.

  • 51% of respondents from India reported that their respective organizations have increased the use of digital technologies and data solutions since the Covid-19 outbreak.
  • Increased staff productivity reported for 74 % of respondents’ organizations with 75% reporting that digital solutions have been effective in delivering better outcomes for patients and service users.
  • Remote consultations, such as, phone and video consultations have witnessed a greater increase in India than the global average. 86 % of Indian organizations are now offering phone consultation (up from 48 % before pandemic) and 83 % for video consultations (up from 33 % before pandemic).
  • Around three fourth of the respondents in India reported positive experiences with digital technologies and data solutions with the number of people using online consultations in India recording a threefold increase.

This encouraging trend and pattern needs to be consolidated, analyzed, and leveraged – for sharper actionable insights for the development of more contemporary products and services to delight the pharma and health care stakeholders.

A key missing link in India:

The digital health transformation of India’s healthcare system during Covid pandemic was also captured in another article, published by Elsevier Connect on February 23, 2021. It reiterated, although the pandemic has made an overall detrimental impact impacted on India, ‘it has brought about an avalanche of positive changes, including the adoption of digital health technologies and significant changes to the way care is delivered.’ Looking ahead, ‘With the launch of national public health initiatives, India has an incredible opportunity to become a digital health leader,’ the paper predicted.

However, the author also pointed out, unambiguously, that the health care crisis caused by the pandemic has also brought to the fore a key missing link – the need for updated and near real-time availability of trusted information. This observation is more relevant now than ever before, especially considering India’s National Digital Health Mission (NDHM).

National Digital Health Mission – a new ambition:

While addressing the nation on August 15, 2020, Prime Minister Narendra Modi announced the National Digital Health Mission of India. He said in his speech, “From today, the national digital health mission will begin. It will revolutionize the Indian healthcare sector. Every Indian will be issued a health ID that will act like a healthcare account, storing details of all the tests done, existing diseases, diagnoses, medicines prescribed.”

The objectives of the mission are to establish a core digital health database, creating a system of Electronic Health Records (EHR) based on international standards, establish data ownership pathways, so that patients become the owner of their health records, and promoting health data analytics and medical research. This initiative by any standard, is expected to be a game changer, as and when it comes to fruition.

Subsequently, on June 25, 2020, the Union Ministry of Health, reportedly, wrote to the principal secretaries (health) of all states and union territories, asking them to extend full support to the NHA to create four registries — doctors, health infrastructure, health IDs and personal health records of patients. It also instructed the states to send the required details within the stipulated timeline without breaching the norms of data privacy.

Need to avoid any possible missing link in the NDHM:

However, the Harvard Business Review article, published on June 12, 2020, asserted that the emergence of the COVID-19 pandemic not only presented a “mind-boggling array of challenges” exposed the limitations of the electronic health record (EHR) in helping physicians deliver care, especially in the United States.

It suggested: transformation of the EHR from an emphasis on a ‘person’s medical record’ – to an emphasis on their ‘plan for health’ and from a focus on ‘supporting clinical transactions’ to a focus on ‘delivering information’ to the provider and the patient, will be more meaningful.

Thus, it’s time for a new kind of EHR system in today’s perspective, as suggested by the HBR article, besides other domain experts. I am sure, competent authorities will take note of this transformation required in EHR initiatives to avoid any missing link in the new digital healthcare space in India.

As the above Elsevier Connect paper also observed, with the launch of national public health initiatives, such as, Ayushman Bharat and National Digital Health Mission (NDHM), India harbors an incredible opportunity to showcase its world class digital health ecosystem for all in the country.

To help fructify these projects, all key stakeholders – health care service providers, its users, and practitioners – including the pharma industry and the tech solution companies, need to get intimately involved with a common agenda in place. Falling behind may invite regrets, later.

Nonetheless, well before that – the common missing links in India - near real-time availability of credible data, trusted and verified information for adopting digital health for patients that will need to be provided by clinicians in a seamless manner, should be carefully identified and addressed.

New steps into digital healthcare are on the way:

Several new steps into digital healthcare have been taken in various countries of the world. One such initiative is ‘Internet Hospitals.’ These are basically an internet-medical-platform combining online and offline access for medical institutions to provide a variety of telehealth services directly to patients.

A Deloitte paper – ‘Internet Hospitals in China: The new step into digital healthcare,’ published on March 16, 2021 says: ‘Online hospitals are typically offshoots of offline medical organizations. The combination of Internet with health care will drive the medical industry’s transformation into a health service provider from a health care supplier, distributing resources equally and enhancing efficiency,’ moving ‘towards future smart health care.’

Conclusion:

Covid-19 has created a new focus on the digital health ecosystem in India, for accelerating the use of digital technology to radically advance health care systems and save lives. Today, many are experiencing that, big data, analytics, artificial intelligence, remote learning, and data inter-connectivity, can make a real difference to the work of HHS professionals in India.

Embracing digital with accelerated speed during the pandemic, has reportedly started making a significant positive impact on the cycle of the patient’s clinical assessment, treatment, and monitoring. With increasing use, it would reduce the cost of health care, improve patient access to affordable treatment and care services, when many patients’ journey for disease treatment will start online, and get directed to the optimal care setting either physically or virtually.

The article on health-tech, published in the Fortune India on February 20, 2021, has aptly concluded: ‘Eventually health technology infusion in the Indian healthcare ecosystem will be the route to enhance patient-centric healthcare accessibility, affordability, and sustainability. The advent of 5G technology in the country is poised to further catalyze this momentum.’ This, in turn, will facilitate ushering in more game changing steps into digital healthcare, creating a new ecosystem, greater awareness and a keen desire to remain healthy for all.

Thus, from the GIGO perspective, as defined by the Cambridge Dictionary, I reckon, in pharma’s digital initiatives, especially in India, a key factor needs to be carefully addressed. This is – fathoming existence of any missing link involving near real-time availability of trusted information and credible data generation, which could indeed be a great spoiler of any painstaking digital adoption project.

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.

 

 

Data Integrity Issue Haunts Again With Covid Vaccine?

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On March 22, 2021, by a media release, AstraZeneca announced that its ‘US Phase III trial of AZD1222 demonstrated statistically significant vaccine efficacy of 79% in preventing symptomatic COVID-19 and 100% efficacy at preventing severe disease and hospitalization.’

Quite unexpectedly, on March 23, 2021, the above claim on AstraZeneca’s Covid-19 vaccine, triggered a rare post-midnight statement by the National Institute of Allergy and Infectious Diseases (NIAID) of the United states. It rekindled a lurking fear of many, yet again, on the issue of questionable data integrity within the drug industry, in general.

This News Release articulated: “Late Monday, the Data and Safety Monitoring Board (DSMB) notified NIAID, BARDA, and AstraZeneca that it was concerned by information released by AstraZeneca on initial data from its COVID-19 vaccine clinical trial.”

The concern was on the possible inclusion of outdated information from that trial, ‘which may have provided an incomplete view of the efficacy data.’ It urged AstraZeneca to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as soon as possible.

Later on that very day, AstraZeneca released another statement saying: “The numbers published yesterday were based on a pre-specified interim analysis with a data cutoff of 17 February. We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis. We are now completing the validation of the statistical analysis.”

The company further emphasized, “We will immediately engage with the independent data safety monitoring board (DSMB) to share our primary analysis with the most up to date efficacy data.” And also added that AstraZeneca intends to issue the results of the primary analysis within 48 hours.

However, the impact of the NIAID’s announcement on the unfurling of AstraZeneca’s Covid-19 vaccine in the U.S, is yet to be ascertained. It’s also still unknown what this news could mean for the vaccine’s alleged efficacy. Be that as it may, it all happened at a time when millions of people, in many countries of the world, including India, have already taken, at least, the first dose of this vaccine.

In this article, I shall deliberate on broader aspects of this critical issue and its relevance in the present case. However, before doing so, let’s try to figure out, why data integrity still remains a major concern of many experts in this area.

Why data integrity is still a major issue:

There are many studies that raised serious concern in this area, over a period of time. For example – ‘Dozens of recent clinical trials may contain wrong or falsified data’ – was claimed by the research paper that was discussed in ‘The Guardian’ on June 05, 2017.

This study reviewed data from 5,087 clinical trials, published during the past 15 years, in two prestigious medical journals – JAMA and the New England Journal of Medicine, and six anesthesia journals. In total, 90 published trials had underlying statistical patterns that were unlikely to appear by chance (or be termed as ‘unforced error’) in a credible dataset, the paper concluded.

Even my own article of September 30, 2019 deliberated on various facets of ‘data integrity’ involving novel therapy, across the world. There, I quoted one of the top medical experts related to the above paper, saying: “It’s very scary that we may be treating patients based on false evidence.” He further added: “It may be the case that certain treatments may need to be withdrawn from use.”

The ghost of a recent example still haunts:

Not so long ago, much reported fallout from Novartis’ alleged data manipulation fiasco with its billion-dollar gene therapy Zolgensma, shook all concerned. So much so, that the Company CEO had to pledge during an investor conference that: ‘the company will be more proactive in reporting data integrity issues to the FDA.’

He also added, Novartis has responded to the FDA’s Form 483 and is making documents available as requested, while reiterating that the data manipulation uncovered at the San Diego site “does not impact the safety, efficacy or quality of Zolgensma.”

The key point to ponder, therefore, especially in AstraZeneca’s Covid-19 vaccine case – is the same ghost haunting us, yet again?

Is it happening again? 

One may, possibly, find some cue of the answer to this question while looking at what followed after ‘validation of the statistical analysis’ by AstraZeneca, as it was promised by the company. Interestingly, the following day, after apparently a thorough analysis, the data released by AstraZeneca, re-iterated effectiveness of its COVID-19 vaccine, which apparently, is broadly similar to the results released earlier.

The Company highlighted therein, ‘US Phase III primary analysis confirms safety and efficacy,’ with the following points:

  • 76% (earlier shown as 79%) vaccine efficacy against symptomatic COVID-19
  • 100% efficacy against severe or critical disease and hospitalization
  • 85% efficacy against symptomatic COVID-19 in participants aged 65 years and over.

It may continue to remain unclear to many – whether or not there was some suspected issue of data integrity – till the answers, at least, to the following questions are made public:

  • Why did the data and safety monitoring board for the trial write a harsh letter to AstraZeneca on its claim, and copied the leadership of NIAID and the Biomedical Advanced Research and Development Authority?
  • As the proof of the pudding is in its eating, why there will even be a slight downward revision in the rate of efficacy of AstraZeneca Covid-19 vaccine?

Conclusion:

I wrote in this blog, way back on August 03, 2015 that data manipulation issues are dangerously leapfrogging into clinical trial domain, even in India. As a result, many domestic drug players had to pay a heavy price – in terms of drug import bans by USFDA and other regulators. Several questions on the quality of efficacy and safety of Indian generic drugs were also raised in many developed countries. A number of best-selling books were also written on this issue.

Some may recall, just ahead Covid pandemic struck, trial data of a highly complex and very expensive gene therapy was also questioned by the US-FDA, for the same reason. However, on March 31, 2020, on completion of its review of the information, records of the inspection, the evidence collected, and the firm’s corrective actions, US-FDA stated: “Objectionable conditions were found and documented but the objectionable conditions observed during the inspection do not meet the threshold for regulatory action.”

Almost in a similar line, after the NIAID decided to make its data related concern public on AstraZeneca Covid-19 vaccine, its head, Anthony Fauci, reportedly, characterized this issue as “an unforced error.” This is indeed a cryptic comment. The root cause of this entire saga with details is still awaited.

Interestingly, the term “unforced error’ is widely used in Tennis, and means, ‘a mistake in play that is attributed to one’s own failure rather than to the skill or effort of one’s opponent.’ From this perspective, after AstraZeneca’s statement of clarification on its Covid-19 vaccine data, the concern on its phase three trial data would possibly be put to rest. At least for now, let’s not see the ghost of data integrity for this vaccine, where there doesn’t seem to be any.

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.

 

Time To Audit Pharma’s Doctor-Engagement And Other Digital Strategies

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It’s now over a year since the unprecedented global health crisis commenced. In this grueling saga, a silver lining is also visible. It helped pharma industry gain a fascinating operational experience, while navigating through disruptive business changes. The changes in the health care ecosystem, ranges from rapid espousal virtual medical care to the meteoric rise of e-marketing and e-visits to physicians.Encouragingly, the entire industry displayed a remarkable resilience to quickly get on to its feet, after initially getting knocked down by the overpowering impact of the pandemic.

One critical pharma-brand demand generating tool – in-person engagement between doctors and pharma reps, also came to a grinding halt – almost overnight, as it were, for well-known reasons. Moreover, companies started facing a crippling situation for all physical business events, such as, Continuing Medical Education (CME), active participation in medical conferences, patient engagements, and so on – as an integral part of their brand or corporate value delivery strategy.

Catching many by surprise, almost in no time, finding no other effective alternatives, several drug companies imbibed e-marketing – many of them in bits and pieces, though. Interestingly, technology based organizational transformation, which was progressing at a snail’s speed, thus far, gained momentum during the pandemic. Since then, there hasn’t been any looking back in this area. Instead, the speed of digital transformation in pharma is expected to accelerate further, as we move on.

Notably, many doctors are still not inclined for in-person sales calls. But, they haven’t stopped looking for product and other information from drug companies. More importantly, after more extensive charting the cyberspace during lockdowns, information requirements of many doctors have changed significantly, as confirmed by various surveys. The same holds good regarding their preferred channels of information and interaction.

This prompts one to ponder over a critical question. Although, a shift towards digitalization, including pharma marketing, is necessary in the changing scenario, do companies need to audit their digital marketing strategies in this area – now?

Nonetheless, this performance audit needs to be an independent assessment of a company’s e-marketing operations to assess whether its digital programs or functions are working as intended to achieve the expected goals. This article will dwell on this subject.

Are companies satisfying doctors’ information needs digitally?

The answer to this question was captured in a recent survey conducted by Abelson Taylor/Veeva. Some of its important findings are as follows:

  • Amid peak of Covid pandemic, 42 percent physicians surveyed, wanted from drug companies, specific treatment protocols tailored to their patient populations. Alongside, they also need to know the latest Covid related developments in medical silences, information on how the outbreak impacts their day-to-day practice, and how they deal with patients. The survey revealed, most of these unconventional information needs were slow to arrive to many doctors.
  • 83 percent physicians reported they hadn’t received any new information from reps, even remotely, in the week before the survey – in late March 2020.
  • Despite reps’ visits being more preferred by doctors, which included e-visits and tele-detailing calls, these declined by 63 percent, while emails between the two increased by 263 percent during the same period.
  • The average time for online meetings is now 17 minutes, despite the above preferences of doctors – versus a pre-Covid average meeting time of just six minutes. One reason could be doctors had more time with them as patient calls were less.

Therefore, the question arises, couldn’t these visits be made more customer need oriented? The possible reason for the same could be lack of simultaneous feedback mechanism for pharma marketers. Similar assessment is essential in other related areas, as well. Because, for reps’ effective virtual ‘visits’, data based – right selection of customer-preferred digital channels, content and formats for communication is crucial.

For Rep’s effective e-visits – channel, content and format selection is vital: 

This area has been well-researched in an India specific article, published by Bain & Company on December 20, 2020. The study found that physicians in India are more likely to engage with certain channels, content and formats for virtual ‘visits’ of medical reps.

The study also found – otherwise, physicians’ click-rates for digital information from pharma companies has traditionally been low – at an average around 10 percent to 15 percent, with some variation for specialties. Thus, with well researched e-visit strategy, pharma companies will have the opportunity to double or even triple levels of engagement in many cases, the study assessed. However, the drug companies would need to necessarily tailor their digital programs to physician preferences.

The study found the preferences of Indian doctors’ in these areas, as below:

Preference

1

2

3
Channel 71% – WhatsApp 20% – E-mail 3% – SMS
Content 29% – Publication findings 26% – Clinical Case Study 12% – Promotional Brand
Format 55% – Videos 15% – Articles and infographics

The above data, therefore, suggest:

-  Physicians in India overwhelmingly prefer communication via WhatsApp, with click rates 3.5 times higher than email and nearly 24 times higher than SMS.

-  Content matters: Scientific content, such as published findings and clinical case studies, generated up to 2.5 times higher engagement than promotional brand content.

- And format makes a difference too, with physicians 3.5 times more likely to click on short video content than articles and infographics.

These vindicate the point – pharma players in India require to initiate a meaningful process of an independent periodic review of their digital strategies – now. More importantly – based on the company-specific emerging trends, if a player quickly adapts accordingly, the possibility of getting a bigger bang for its buck on physician outreach,’ would likely to be high – even in the new normal.

Some key points to consider during long-term digital strategy formulation:

Just as today’s pharma operations aren’t a replica of 2019 and before, the same holds good for tomorrow and thereafter, as the process, span and magnitude of digitalization will keep improving. A glimpse of the same is available in an article on digitally engaged physicians during the digital health transition, published in PLOS ONE, on September 28, 2020. Following are the two – among several other points, on further democratization of medical information, as articulated by the authors:

  • Broader role of doctors is during the digital transition. Companies need to spot and understand quickly how it’s evolving over a period of time.
  • Digitally engaged physicians may also consider themselves as a guide and participate in the medical information managing function – in the description, collection, and sharing of credible content in the online space.

Conclusion:

Nevertheless, a section within the pharma industry still nurtures the hope of a return to the ‘old normal.’ Whereas most others don’t really subscribe to this seemingly unrealistic hope. Hence, even after the pandemic gets over, some critical changes are likely to last longer. These include more e-visits of reps than in-person doctor calls, webinars for doctors and patients, in company virtual meetings for training and other strategic physical events. None of these are expected to happen in similar frequency, scale and manner as what used to happen in 2019 and before.

Further, in the new normal, with more enlightened and digital savvy customers around, just talking the talk of ‘patient-centricity’ will no longer suffice. Companies will need to walk the talk - mostly through more transparent digital platforms, henceforth. Similarly, just talking about data and analytics won’t just be enough, pharma companies need to marshal enough wisdom in their people inventory, to capture and make productive use of credible data and information.

Undoubtedly, pharma’s digital strategies in all these areas have started taking roots. However, the yield of the same, apparently remains much below their potential, in most cases, for various reasons. Which is why, I reckon, an independent, in-depth, and periodic audit of each pharma company’s doctor-engagement and other digital strategies, since the onset of Covid-19 pandemic, is now essential.

The objective is not to revert to the old traditional model – jettisoning the digital transformation pathway, especially in pharma marketing, especially when the yield is low. The idea is to review or redraft the digital strategy, based on periodic audits. Or it may even be just tightening some loose knots of a patient-centric and doctor-friendly contemporary game plan for business excellence in the new environment.

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.

 

Restart Pharma Demand Generation Activities With Actionable Insight

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As the ‘Lockdown. 04’ in India passes by, a time comes to press the restart button of all business activities in the country, in a calibrated manner, though, keeping in mind, the Covid-19 cases is yet to find its peak in the country. The process would naturally include all activities of the pharma industry. And more specifically, the prescription demand generation activity, where personal selling has remained pivotal in all these years.

But now, while living with the new Coronavirus, it would require greater cerebral interventions of astute pharma marketers. Creating an innovative pathway for recovery – driven by actionable insights, through an agile and digitally empowered workforce, would be the name of the game for success. In this article, I shall focus on this important area, as the industry moves on.

The bedrock of the new pathway:

The ‘restarting’ process of the prescription demand generation mechanism, I reckon, would no longer be the same ball game. It will now entail gaining cutting-edge actionable insights on the evolving dynamics of the changing business processes. It involves customers’ new preferences for consumption in the healthcare space and ascertaining the most effective demand generation processes or tools in the prevailing new normal.

Therefore, the bedrock of the new pathway, in my view, will necessarily need to be based on:

  • A huge pool of relevant, credible and preferably real-time ‘Data.’
  • ‘Information’ obtained by analyzing the ‘Data’ as desired.
  • ‘Actionable Insight’ gathered from the collected ‘information.’

The encouraging point is, several companies, even in India, have already started testing the water to chart the way forward.

Some fundamental changes in the path to recovery:

The McKinsey article of May 12, 2020 titled, ‘Pharma operations: The path to recovery and the next normal,’ also noted: ‘Given the shifts that have taken place seemingly overnight in response to the immediate crisis, companies are also turning their attention to recovery and the path to the next normal. It will likely bring about fundamental changes in pharma operations.’

Besides, the future of work will become more remote and distributed, and demand may shift to new capabilities and talent. Moreover, ‘the post-COVID-19 workforce and organization will also likely adopt new, more efficient ways of working.’ Thus, pharma organizations should consider adapting quickly in the path to the next normal, the article added.

The change and increasing relevance of ‘Data’, ‘Information’ and ‘Insight’: 

While discussing about ‘Data’, ‘Information’ and ‘Actionable Insight,’ let us first try to understand the differences between each of these three. Voccii, the US based market research firm, captured this difference eloquently, as follows:

  • Data: the raw and unprocessed facts, captured according to some agreed-upon standards. It could be a number, an image, an audio clip, a transcription, or similar.
  • Information: the data that has been processed, aggregated, and organized into a more human-friendly format. Data visualizations, reports and dashboards are common ways to present information.
  • Insight: gained by analyzing data and information to understand the context of a particular situation and draw conclusions. Those conclusions lead to actions that one can apply to business operations.

To facilitate the process of desired changes, translating research data into actionable insights will now be a crucial strategic input. In fact, these are essential while recomposing notes in pharma sales and marketing playbook, more than ever before. Notably, it has now been established in other industries that actionable insights facilitate prompt business process transformation, putting the organization ahead of competition for excellence.

What really are ‘actionable insights?’

Although, these two words are self-explanatory, it’s better to reiterate again – what ‘actionable insights’- based ventures are. It will help all to be on the same page while reading this piece. As I understand, ‘actionable insights’ mean gaining an accurate and deep understanding of someone or something or some situation based on relevant and credible data, that can help generate specific actions for a successful outcome.

However, what generally happens instead, and particularly in the Indian pharma industry, is usually very different. Quite often, many marketers get drowned in a large pool of available data and information, sans the cerebral skill of gaining actionable insights out of those – they start relying more on their ‘gut-feel’. As a result, ‘gut feel’ driven actions try to be in the driver’s seat, rather than data-based ‘actionable insights’ of high value.

Digital insights would be ‘The new currency of business’ in the new normal:

Today, it’s not quite uncommon to find pharma companies, especially in India, having loads of data and information. What they perhaps need to learn is, how to convert those inputs into actionable insights, the lack of which could make even the best of market research initiatives unproductive. That’s why, around the world, many believe that Digital Insights Are The New Currency Of Business. More so, in the new normal of living with Covid-19.

The article – ‘Actionable Insights: The Missing Link Between Data And Business Value,’ published in Forbes on April 26, 2016 also emphasized this point. It said. ‘With many companies struggling to make sense of their data and create value with their big data investments, the promise of actionable insights sounds wonderful. Forrester reports 74% of firms say they want to be “data-driven,” but only 29% are actually successful at connecting analytics to action. Actionable insights appear to be the missing link for companies that want to drive business outcomes from their data.’

Harvesting insights from data can fetch huge financial returns for the company. Which is why, sitting at the apex of the data pyramid, actionable insights help drive strategic action. It prompts rethink the status quo, pushing marketers to move into a new strategic direction. From this perspective, in the new normal of living with Coronavirus, actionable insight based unique brand strategy, content development and the process for reaching out to patients, doctors and other health care consumers, I consider, will decide the degree of business success.

Some focus areas for ‘actionable insights’ in the changing scenario:

Although, ‘actionable insights’ would help strategize a whole new chain of activities for increasing ‘prescription demand generation,’ some of these areas, for example, may include:

  • Capturing changes in patients’ behavior and preferences, specifically during the national ‘Lockdown’ period, besides, ‘compliance to social-distancing’ norms.
  • New ways of regrouping patient population, alongside, effective content creation and choosing right platforms for a sharper focus on them in the new situation. 
  • Doctors’ changing preferences for interacting with drug companies for the same reasons.
  • Making remote prescription demand generating actions highly productive, ensuring a cutting-edge over the competition.
  • Taking a quantum leap in improving the level of engagement for a greater share of mind with doctors, patients and other stakeholders, without bombarding them with ‘me-too’ emails, messages and calls. 

Conclusion:

As the ‘Lockdown. 04’ in India – the second most populous country of the world – ends, as on May 31, 2020 morning, the recorded Coronavirus cases in the country reached 182,490 with 5,186 deaths. Comparing the same with the most populous country of the world – China, where Covid-19 struck first ever – in December 2019, one finds it recording 83,001 cases with 4634 deaths, on the same day.

Be that as it may, after the national ‘Lockdown’ of about two and half months to save lives, it’s about time to restart initiatives for the livelihood of millions of Indians. Accordingly, pharma industry would also hit the restart button of its all business activities in the country – understandably, in a calibrated manner. The restart would include one of its most critical activities – generation of prescription demand, where personal selling has been pivotal in the years passed by. Several research studies have already highlighted a changing pattern in this area.

In the coming days of work while living with Covid-19, all would need to take measures to prevent the Coronavirus infection. Thus, strict compliance with the social distancing guidelines and other norms, as prescribed by the Government, will be ne necessary for all. This would also make the working life of pharma professionals, along with the practices of its stakeholders, significantly different from the traditional past.

From this perspective, while reaching for the restart button in the new normal, pharma sales and marketing leadership would need to create an innovative pathway to recovery. This would call for actionable insights about changes in the behavioral and preference pattern, especially of the healthcare consumers and providers. These will be absolutely critical for commercial success in the ‘new world,’ as it were – more than ever before.

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.

A New Facet of ‘Data Integrity’ With Novel Therapy… And Much Beyond

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The peril of breach of data integrity involving a top Indian pharma player, jolted many, probably for the first time, on September 17, 2008. On that day, the USFDA, reportedly, issued two ‘Warning Letters’ and an ‘Import Alert’. These were related to deficiencies in the drug manufacturing process and deviations from U.S. current Good Manufacturing Practice (cGMP) at Ranbaxy’s Dewas and Paonta Sahib plants in India.

Since then, instead of demonstrable corrective measures, similar incidents had started ballooning – inviting more serious US-FDA actions, such as Import ban, consent decree, loss of market value, Loss of customer trust, among many others. The research article – ‘Overview of Data Integrity issues in the Pharmaceutical industry,’ published by the International Journal of Pharmaceutical Sciences Review and Research, in its May-June 2018 issue, also reflects the same trend.

Much reported instances of breach of ‘Data Integrity’ were specific to generic drugs and mostly manufactured by Indian companies, besides China. While this may be true at that time, it is now spreading much beyond generic drug manufacturing in India and China – making its way into the global clinical trial arena. I also wrote earlier that ‘Data Manipulation: Leapfrogging Dangerously Into Clinical Trial Domain.’ With greater focus, this article will discuss not just how ‘Data Integrity’ issue is cropping up into clinical trials of even modern, complex, highly innovative and exorbitantly priced lifesaving treatments. Going beyond that, I shall also point towards increasing attempts to exaggerate the success of many cancer drug trials due to strong bias. Nevertheless, let me start by rehashing the relevance of ‘Data Integrity’ on patients’ health interest.

Data Integrity ensures safe, effective and high-quality drugs for patients:

According to US-FDA: ‘Data integrity is an important component of industry’s responsibility to ensure the safety, efficacy, and quality of drugs, and of FDA’s ability to protect the public health.’ Thus, data integrity-related cGMP violations may lead to regulatory actions, including warning letters, import alerts, and consent decrees, as the drug agency notified. In other words, maintain all types of ‘Data Integrity’ is a key requirement in the pharma industry to demonstrate that the final products conform to the required quality parameters.

These requirements are known to all generic drug exporters catering to the regulated markets, including the local manufacturers in the United States. Curiously, it continues to happen despite their full knowledge of the grave consequences of violations. The June 12, 2019 paper – ‘An Analysis Of 2018 FDA Warning Letters Citing Data Integrity Failures,’ published in Pharmaceutical Online, brings out some interesting facts, related to drug manufacturing area.

From the analysis of 194 ‘Data Integrity’ associated ‘Warning Letters (WL).’ from 2008 to 2018, the top 5 countries in this regard came out as follows:

Rank

1

2

3

4

5

Country

China

India

United States

Europe

Japan

No. of WL

58

54

36

14

7
% to Total

29.8

27.8

18.6

7.2

3.6

Interestingly, over 76 percent of US-FDA Warning Letters (WL) are on manufacturing ‘Data Integrity’ and were issued to pharma companies located in China, India and the United States. Moreover, when it comes to all types WL related to various types of regulatory malpractices, India again featured as one of the top violators. Be that as it may, I shall now focus on the spread of this decay in other important drug safety related areas, such as clinical trials.

Ironically, breach of ‘Data Integrity’ in another crucial area, like clinical trials for new drugs, doesn’t seem to attract public attention as much, which I shall reason out below – also explaining why it’s so.

Breach of ‘Data Integrity’ in clinical trial – more crippling for the company: 

‘Data Integrity’ concern pertaining to clinical trials was recently expressed in an article, published by the Food and Drug Law Institute, in the April-May 2019 issue of its Update Magazine. The paper reiterated: ‘Good Clinical Practice (GCP) data integrity issues can at times be more crippling to a company than Good Manufacturing Practice (GMP) data integrity issues.’ Elaborating the point further, the authors highlighted, where such issues are severe, the drug regulatory agency may completely reject the data submitted in new drug applications, supplemental drug applications, and abbreviated new drug applications.

This outcome is quite akin to import bans for generic drugs into the United States, as it would cause a huge setback for the company, affecting clinical development programs for the new drug. Moreover, as the article says, such action would be ‘costing the sponsor substantial time, money, and reputational credibility, not to mention delaying patient access to new drugs.’

‘Dozens of recent clinical trials may contain wrong or falsified data’:

This is claimed by the research paper that was discussed in ‘The Guardian’ on June 05, 2017 carrying the headline - ‘Dozens of recent clinical trials may contain wrong or falsified data, claims study.’

In this study, John Carlisle, a consultant anesthetist at Torbay Hospital, reviewed data from 5,087 clinical trials published during the past 15 years in two prestigious medical journals, JAMA and the New England Journal of Medicine, and six anesthesia journals. In total, 90 published trials had underlying statistical patterns that were unlikely to appear by chance in a credible dataset, the review concluded.

As one of the top medical experts quoted in this paper, said: “It’s very scary that we may be treating patients based on false evidence.” He further added: “It may be the case that certain treatments may need to be withdrawn from use.”

Another October 01, 2013 report, citing a specific example of the same, wrote: ‘Japan’s ministry of health has concluded that studies based on clinical trials for Novartis’s blood pressure drug Diovan contain manipulated data.’ It also added: ‘Diovan was approved for use in Japan in 2000, but recently two universities who hosted and analyzed trials for Novartis – the Kyoto Prefectural University of Medicine and Jikei University School of Medicine – reported finding evidence of data fabrication.’

Thus, from available reports, it appears, just as the saga of ‘Data Integrity’ related drug manufacturing keeps continuing, the same related to clinical trials doesn’t seem to fall much behind. But, the valid question that may follow – why then reported instances of breach of clinical trial data integrity isn’t as many?

Breach of ‘Data Integrity’ found by USFDA is rarely reported: 

The answer to the above question may be found in The BMJ study, published on February 10, 2015. It brought to the fore – ‘Research misconduct found by FDA inspections of clinical trials is rarely reported in journal studies.’ This review was based on identified 57 published clinical trials for which an FDA inspection of one of the trial sites had found significant evidence of research misconduct, including falsification or the submission of false information, problems with adverse event reporting.

The researcher also noted that serious misconducts related to clinical trials, are rarely mentioned in subsequently published journal articles in the same area. More disturbing to note, this critical gap in the transparency of clinical trial reporting is now sneaking into even highly specialized treatment, such as ‘Gene Therapy’, and that too involving a Big Pharma name.

US-FDA has now raised this question even for a ‘Gene Therapy’:

A media report of September 09, 2019 highlights, that Novartis is facing an uproar over data manipulation involving USD 2.1 million gene therapy Zolgensma, which treats spinal muscular atrophy, a leading genetic cause of death in infants. According to this report, Novartis gave “detailed explanations” on Aug. 23 to the FDA about the company’s investigation into the data manipulation and addressed regulators’ questions over why the company waited until late June to make disclosures. However, quoting the FDA, the report indicates, ‘Novartis could face possible civil or criminal penalties.’

Prior to this, another report of August 13, 2019, stated that ‘documents referenced in a Form 483 by the FDA, which inspected the lab a month after it learned of the falsified records, also suggest the data-fudging began at least in early 2018 and could have been uncovered by managers at AveXis during several steps in the clinical outcome assessment.’ The gene unit of Novartis is called AveXis, which had announced the US-FDA approval of Zolgensma on May 24, 2019.

Such instances involving clinical trials with new, complex and highly innovative therapies, further reinforces already existing ‘Data Integrity’ related health safety concern. The cost of these new treatments being so high, it’s perplexing to fathom the necessity of cutting corners in clinical trials, if at all. More so, when these are avoidable to establish efficacy, safety and high-quality standard of the therapy to drug regulators for marketing approval.

Beyond ‘Data Integrity’ – in clinical trials:

Just as ‘Data Integrity’ issue in generic drug manufacturing has intruded in the clinical trial arena for novel treatments, yet another concern, also related to data, goes much beyond what is happening today in this area. This fast-emerging practice is related to ‘cherry-picking data’ for biased clinical trial reporting, adversely impacting public health safety, as brought by several research studies.

Very recently, this was vindicated by another paper published in The BMJ on September 18, 2019. It raised a serious concern of bias in clinical trial data submitted to regulatory agencies for marketing approval of even lifesaving drugs. The findings of the above paper concluded:

Between 2014 and 2016, almost half of the most pivotal studied forming the basis of European Medicines Agency (EMA) approval were judged to be at high risk of bias, based on their design, conduct or analysis. Accepting that some of these might be unavoidable because of complexity of cancer trials, it noted that regulatory documents and the scientific literature had gaps in their reporting. Journal publications also did not acknowledge the key limitations of the available evidence identified in regulatory documents. This concern too keeps growing.

Conclusion:

As discussed above, six broad and important points to note for any ‘breach of integrity’ or ‘cherry-picking’ of data in the pharma industry:

  • Takes place mostly in two known areas – manufacturing and clinical trials.
  • Involves both cheaper generic drug manufacturing, as well as, clinical trials of most innovative and highly expensive treatments – conducted even by Big Pharma constituents.
  • ‘Cherry-picking data’ for biased clinical trial reporting while obtaining marketing approval, involves even cancer drugs.
  • Any such avoidable malpractices with ‘data’, could seriously impact patients’ health interest, raising a public concern.
  • Instances of such malpractices usually become public, only when the perpetrators are caught by vigilant drug regulatory agencies, such as the US-FDA, or when external experts can trace their footprints through sophisticated analytical tools.
  • Multiple instances of wrongdoing of this nature, often by the same company, despite requisite regulations being in place, and also after facing penal actions, make it mostly a self-discipline issue of repeat offenders.

It’s a different discussion all together, whether or not ‘data’ is a new oil – air or water. But maintaining the sanctity of data, while generating, interpreting, presenting or even leveraging these, including for commercial considerations, must not be compromised, at any cost.

Today, breach of ‘Data Integrity’ and ‘Cherry-Picking of Data’ for biased reporting, are creeping into new drug clinical trial domain – from its usual habitat of generic drug manufacturing, posing a greater threat to patient safety. At the same time, none can say, either, that it’s happening with all drugs, at all the time and by all drug manufacturers. But, if and when it happens, it could lead to a catastrophic consequence both for patients and their family.

Be that as it may, country’s top drug regulators should strive harder for an ongoing and meaningful engagement with the pharma industry on this avoidable development. It could well be a carrot and stick approach, where repeat violations by any company would pose a risk of legal survival of the business.

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.