BMT means transplanting one’s own diseased bone marrow with healthy bone marrow. Your bone marrow is destroyed using radiation or/ and cytotoxic drugs first, then healthy bone marrow/ umbilical cord blood is transfused. This procedure results in regeneration of healthy marrow, which cures the disease.
Since bone marrow is responsible for the production of all white cells, red cells and platelets, BMT is used for treating leukemia (blood cancer) and some forms of anemia.
Benefits and limitations of BMT
To understand this, it is necessary to know some basic hematology. The bone marrow is the only tissue in the adults which produces all cellular components. In the adult humans it is distributed in several parts of the body viz. skull, sternum and pelvic girdle (iliac crest). This tissue continuously produces the red cells and white cells which are lost regularly, for the entire life of the individual. This is possible due to the presence of a small number of “Stem cells “. The stem cells are located in the “ niches, present only in the bone marrow, which have the unique property of “ self renewal “, which makes it possible to maintain their population, while contributing cells for differentiation to blood cells all through the life of the individual. During the transplantation process the stem cells travel through the blood stream and by a very complicated process reach the bone marrow stem cell niche, where they establish themselves and start dividing. One of the two daughter cells remain as stem cells and the other undergoes division and differentiation to give rise to mature functional blood cells.
Leukemias are caused due to mutations in the stem cell population and therefore, the only effective way to treat blood cancers is by bone marrow transplantation. Similarly, some anemias like fanconi’s and thalasseamias are due to stem cell defects and the only effective way to treat these diseases is by transplanting with normal donor bone marrow.
Though BMT is a very effective, it has some limitations. The most important being HLA(Human leukocyte antigen) compatibility. All the cells in the body display these markers on the cell surface which determines “Self and Non self”. No two individuals except identical twins have the same HLA markers. In the general population, it is like finding a needle in the hay stack. When a mismatched graft is transplanted into a host, rejection takes place and results in “ Graft versus Host disease”, a severe life threatening reaction.
The number of bone marrow cells transplanted is always very high because the process of stem cell homing into the host marrow niches is random. Most of the cells are lost in the lung and liver never reaching the bone marrow. This puts a severe restriction on the size of the donor sample.
The process of transplantation involves destruction of the marrow cells by radiation and chemotherapy which results in severe neutropenia and immuno suppression which may lead to life threatening complications. These patients need to be kept in sterile living conditions, which results in huge expenses.
Can Umbilical cord blood stem cells substitute for donor marrow
Umbilical cord blood is the residual blood present in cord after the baby is delivered. This has been known to contain stem cells similar to the marrow.
These stem cells are superior to the bone marrow derived by virtue of their multipotence and reduced expression of HLA markers, making them less prone to rejection in spite of HLA mismatch. Several national and international studies have shown that successful regeneration of marrow takes place when umbilical cord blood is used for transplantation.
Another major advantage is that, the cord blood can be collected at the time of birth and cryo preserved in bank. The stem cells can be HLA characterized and a registry can be made. Whenever a stem cell is needed for transplantation, appropriate sample can be thawed out and used for transplantation. This greatly improves the chances of finding an appropriate stem sample for transplantation. These are the public cord blood banks. However, unfortunately, another form of banking cord blood has become more prevalent especially, in India viz. the autologus cord banking also known as private cord blood banks. These banks cryopreserve umbilical cord blood of your child for your own child’s use, at any time in the future, for a fee. Though, this type of banking has limited use as a source of stem cells since it cannot be used for transplantation in case your child develops any of the stem cell derived diseases.
Autologus bone marrow transplantation
Autologous bone marrow transplant means using the bone marrow of the same person for transplantation. This is possible when the person’s bone marrow is healthy. This procedure is used in the treatment of solid tumors which do not affect the bone marrow. This is actually a rescue procedure. One of the major limitations of chemotherapy is that it kills normal cells along with the cancer cells. The given dose is so adjusted that the cytotoxic drug does not kill the normal cells. One of main tissue which is affected is bone marrow, resulting in anemia and nutropenia, which may become life threatening. Therefore, it has to be protected, if the dose of the cytotoxic drug has to be increased, which is often needed since cancer cells can become resistant to the drugs. One of the ways by which this is done is by mobilizing the stem cells from the marrow by injecting the patient with a growth factor called Granulocyte colony stimulating factor(GCSF) and collecting into a sterile bag which will be cryopreserved. After the increased dose of drug is given the stem cells are re-infused.
What is Stem cell transplantation
The bone marrow contains stem cells which give rise to blood cells normally; but can also result in other tissue cells. This property makes them useful in regenerative medicine.
Another type of stem cell which is found in bone marrow, is the Mesenchymal stem cells. These cells have been shown to be important in regenerative medicine.
Defending premium pricing is a challenge for pharmaceutical & medical device players globally. With the increasing tendency of governments worldwide intervening and attempting to make healthcare services more affordable and inclusive, this challenge continues to push companies to develop innovative strategies in marketing.
Stakeholder engagement through medical marketing strategies with appropriate planning and execution can lead to sustained value creation beyond product for which customers are more than willing to pay. This paper presents the planning and execution process of medico-marketing strategies for enhanced customer engagement and improved business outcomes.
Medical marketing strategy, Physician engagement, Key opinion leader, Medicomarketing, pharmaceutical, medical devices, Medical marketing strategy formulation process
During the past decade, the pharmaceuticals and medical device business has undergone a paradigm shift from a collection of transactional events between the physician and a seller of product, to the continuum of care that includes a larger universe. In this continuum, medical product companies have been steadily expanding their role to have wider positive impact on their stakeholders. The pharmaceutical industry is no longer being rewarded for incremental innovation, me-too products and selling pills or devices. Companies need to demonstrate that their brand adds value to customers and they offer a value beyond product/service. A valued solution that a customer not only wants and needs but is willing to pay a premium for!
With pressures of squeezing margins in mature markets, incremental growth in marketing expense is perceived as an additional burden on the bottom lines.
Figure1 illustrates that the pharmaceutical industry spends more than $27 billion on drug promotion, [i]more than $24 billion on marketing to physicians and over $3 billion on advertising to consumers (mainly through television commercials). The numbers are increasing year on year. The total spending on prescription medicines has surged by 13.1% in 2014, to $373.9 billion.
Figure 1. Expenditure by type of pharmaceutical marketing
In emerging markets, like India, global pharmaceutical players have been quite successful in penetrating the market. The Indian drugs industry, which is valued at US$ 25.87 billion at present, according to Care Ratings, is also expected to grow in the local market with aggressive rural penetration by drug makers, increased government spending on health, and growing health awareness among people.[i] Unlike pharmaceutical companies, global players in medical devices and Equipment industry have not found great success in penetrating the market given the same market situations and challenges. The Indian medical devices and Equipment industry valued at US$ 2.5 billion contributes only 6% of India’s US$ 40 billion healthcare sector.[ii] FICCI (Federation of Indian chambers of commerce and industries) in its report identified key challenges in the medical devices and equipment industry which are low penetration, low accessibility and low awareness. 2 In the same report FICCI’s recommendations to overcome these challenges were to increase the quality and enhance consistency of training received by medical and paramedical staff thereby providing creative resources for leading medical innovation efforts and to encourage greater collaboration between medical centers and technology universities. Such recommendations are important to keep in mind for planning of customer engagement strategies. In emerging markets, innovations in medico-marketing strategies have shown tremendous impact on the pharmaceutical business. Patient empowerment, wearable technologies, use of predictive biomarkers, virtual reality apps linked to healthcare, patient data security, privacy and accuracy etc. are few of the newer trends adopted by global pharmaceuticals to move from product-centric approach to a more patient-centric model. Customer centric strategies will help medical devices companies to increase penetration in emerging markets. Various strategies for customer engagement have been deployed by healthcare players. Physician and company representative engagement is the most obvious and still remains the core activity of pharmaceutical or medical devices companies. But different methods/channels of customer interactions may lead toy opportunities which converge into a multipronged engagement strategy. Let’s look at the two basic types of these engagement models.
This is a conventional engagement between a company representative and the physician which develops through the in-clinic interaction. Here, the company representative is a medium or channel. Very often this is a one sided communication about the disease, therapy and USP of the drug or device.
Majority of the Pharma marketing budgets are spent on this method which focusses on one customer which is the physician and one medium that is the sales representative.
This engagement is typically transactional in nature.
Using this approach healthcare solution providers or product sellers can engage multiple customers through multiple mediums.
Different type of customers like physicians, paramedics, patients, pharmacists, healthcare institutes can be engaged by using various channels or mediums like digital or online, mobility, social media and print or web advertisements.
A well thought out Medico-marketing strategy helps companies leverage diverse mediums for multidirectional engagement.
Different Engagement models that are being leveraged by pharma marketers are depicted in figure 2 below.
As mentioned above, conventional customer engagement is transactional in nature through which company representatives are perceived merely as product sellers by doctors. Globally, customer engagement and more specifically physician engagement has been under the scanner. In United States, under the Sunshine Act that is part of Patient Protection and Affordable Care Act, manufacturers have to report all payments for research, travel, honoraria and speaking fees, meals, educational items like textbooks and journal reprints.
Comparison of Spend on marketing strategies for customer engagement in transactional approach and partnership approach is depicted in figure 3.
In a transactional engagement, initial returns are higher but diminish over period of time and are difficult to maintain longer.
In a partnership approach, sellers transform themselves to take up a broader role so that doctors perceive them as partners in their clinical practice. In such an engagement, initial investments are higher but returns steadily increase and are better sustained as time progresses.
Figure 3. Engagement return on investment over a period of time
Customer engagement for sustained value creation around the core product
A healthcare marketer must influence multiple stakeholders to shape or expand the market. Physicians are the main decision makers in most of the situations, but inherent differences between devices and a pharmaceutical drug must be kept in mind. Efficacy of medical devices/technologies relies on the skills and experience of the physician, the quality of the hospital, and many other factors (which is not the case with pharmaceuticals due to their chemical nature – it either works completely or doesn’t work completely).
Apart from physicians other customers are paramedical staff like nurses, physiotherapists, and respiratory therapists who are the end users for a product. Patients are most often the end beneficiaries of the product or service. For medical equipment business, engineers become important influencers from service & maintenance contract perspective.
Very often, with a strong focus on external customers, internal customers within an organization are ignored. But, for successful implementation of strategy and to have a positive impact on the business it is imperative that internal teams, especially the sales team owns the medico-marketing strategy and drives it in respective territories & customers.
An important prerequisite for building medico-marketing strategies is to identify and prioritize the type of customers with whom to engage. It is difficult to target all the customers with one strategy at any given time. Still, strategic initiatives can be designed to be more inclusive in terms of customer involvement. For example, training curriculum for nurses can be prepared by physicians and later executed in the form of series of workshops with the help of the sales team. Thus, with just one initiative three different sets of customers (Physicians, nurses and sales team) can be engaged.
Customer engagement is a long term process with tactical spur of activities based on the business plan or product life cycle stages. Figure 4 summarizes the different avenues of physician engagement throughout the product life cycle.
Figure 4. Physician engagement helps product life cycle management
Physician engagement that begins at the product discovery stage pays rich dividends. With proper customer engagement, pharmaceuticals can understand the geographic market real needs and these clinical insights from physicians can help them capture maximum of the market with better sales. Johnson and Johnson has developed a knee implant suitable for the Indian market as well as a reusable stapler for use in surgeries at price points, which are amenable to the Indian market. Roche Diagnostics has developed a screening device for cardio-vascular diseases, which is suitable for use in rural settings.
Philips Healthcare is using its recent acquisitions in India to develop and launch a low cost cardiac catheterization laboratory for the Indian market.
Similarly at every stage of the product, customers can be engaged through a blended strategic mix of medical and marketing strategy.
Medico-marketing strategy & customer engagement
While a well-designed medical marketing strategy can enhance customer engagement, it is also true that customer engagement can lead to robust medical marketing strategy formulation.
Process of building a medico-marketing strategy
An 8-step framework for building medico-marketing strategy is summarized in figure 5.
Figure 5. Medico-marketing strategy formulation process
For a better understanding of the process, let us look at one type of customer – the Physician and build a process template that can then be applied to different customers as well. The process represents a true ‘democratic way of strategy formation’ in which physician ideates, plans and partners to execute the strategy along with the healthcare product marketer leading to Medico-Marketing: Of the Physician, by the physician, for the physician.
The eight step process of medico-marketing strategy formulation is described below:
Overall business strategy
Medical marketing initiatives have their origins in the overall corporate business strategy. In fact, to ensure success they must be aligned with the overall business strategy.
Case 1: Business objective of a medical device global leader was to increase market share by increasing the customer base and become a market leader in airway management products in India. The goal of medico-marketing strategy therefore, was to increase customer adoption of airway management products. To achieve this, end users i.e. paramedical staff were engaged in a yearlong training program on product usage which helped the company achieve market leadership.
Decide the customer engagement objective
One of the important outcomes of a medical marketing strategy is successful and sustained customer engagement. The organization and concerned internal stakeholders must identify the tangible objective behind such customer engagement.
Case 2: A MNC leader in prevention of migraine in India- The objective was identified so as to move away from being just a pill provider for the neurologists and become the therapy leader in migraine prophylaxis. Thus, an initiative called LEAD (Let Education and Awareness Defeat) migraine was launched. Under this medical marketing project, Key neurologists across the globe were engaged and education CME (Continuing Medical Education) seminars for doctors and patient education on migraine prevention was successfully carried out.
Create engagement platform
The first step towards building a customer centric strategy is to bring key customers together on a single discussion platform.
It is very important that the theme of the platform reflects the shared purpose and goal of the company and its customers.
For example, themes like enhancing patient outcomes inspire both physicians as well as healthcare companies which have a patient centric vision.
Customer need Identification
An unmet customer need provides not only a lead for product development but it is also an engagement opportunity. Brainstorming with customers is a good way to generate real time insights about customer needs. Figure 6 depicts few universal needs of any physician. Note that these are applicable to clinicians of all specialties across all geographies.
Figure 6.Few universal needs of a physician
Customer need Prioritization & selection of focus area
Focusing on multiple needs of Physicians can be a challenge for any organization.
Identification of commonalities or similar purpose between needs of an organization and the needs of physicians is helpful in determining which needs to focus upon. Such common needs become priority needs (P-need) and this P- need becomes the origin of medico-marketing strategy. This concept is represented in the form of a simple Venn diagram in the figure 7.
Figure 7. Identification of P- need
This is applicable at all levels: Organization or SBU or a brand. A P-need can be identified at a company level, corporate advisory board level or with key thought leaders at any specific brand level.
A Global leader in tracheostomy tubes wanted critical care specialists in their key geography to use their tubes which required a special technique.
Critical care specialists were keen to learn new techniques so as to enhance their clinical skills.
Hence, this tracheostomy tube provider engaged a key opinion leader and tied up with a simulation training center which provided hands on training to critical care specialists on new techniques of tracheostomy. The strategy was beneficial for the company as well as for the clinicians.
Build medico-marketing initiatives
Projects/initiatives which originate from unmet needs of the physicians are more relevant and are realistic to their practice.
A leader in airway medical devices in India partnered with top critical care specialists across India to develop an innovative educational initiative for paramedical staff to bridge the knowledge gap in Ventilator Associated Pneumonia (VAP) prevention practices.
Through this initiative a team of 500 nurse educators was formed and 4500 nurses were trained within a span of one year.
Listening to and responding to the ‘Voice of the Customer’ (doctors) and the need of India’s patients – a MNC launched a patient assistance program called SPARSH (which means ‘touch’ in Hindi), which has touched 20000 patients over 110 towns in India. The program is offered to patients taking anti-diabetic medications upon recommendation from the prescribing physician. It offers comprehensive diabetes management including diet counseling, exercise counseling, education on diabetes and its complications all of which is delivered via a call center in Hyderabad, India.[i]
A MNC has launched Arogya Parivar (which means ‘healthy family’ in Hindi), to tap the bottom of pyramid population of India. It offers improved healthcare for 42 million people living in 33 000 villages, expanding their access to affordable products, improved health infrastructure and community education. It began returning profit within 30 months of its launch and since 2007, sales have increased 25-fold.[ii]
Customers drive medico-marketing initiatives
If physicians are involved in the planning of medico-marketing initiatives right from the beginning then their ownership and motivation levels are high. Clinicians themselves drive these initiatives in their respective hospitals using their sphere of influence.
A Medical Device Company needed to shape and prime the market for their innovative ambulatory pain management device which offered patient controlled analgesia and better patient satisfaction.
Anesthetists and Pain specialists in their KOL close group meeting with this Medical Device organization brainstormed about the current situation on pain management. They shared that in general, anesthetists and pain specialists felt the need of such innovative device but hospital management and surgeons were not in favor of this device due to fear of rise of the cost of surgery. During the same closed group meeting, anesthetists proposed that they needed to collaboratively prove to hospital management as well as operating surgeons about the deficiencies and low level of patient satisfaction with the current pain management practices. These group of anesthetists happily volunteered to play the role of investigators in a patient survey on pain satisfaction. This multi-country, multi-centric pain satisfaction survey with 1200 patients was first such attempt from Asian countries engaging 15 key institutes with great mix of academic institutes like AIIIMS (Delhi), PGI (Chandigarh), National hospital (Colombo) and private corporate hospitals like Apollo and Fortis. Through this initiative, along with top KOLs in the region, top hospitals were also engaged by medical device organization. KOLs from south Asia also authored an international publication which helped the organization to shape the market for their innovative pain management device.
Monitor, Improve and revise strategy as per the objective
Medico-marketing initiatives are most often long term projects and require project management skills to drive their timely completion and continuous feedback loops to plan for future initiatives.
Horlicks was the most trusted drinks brand of India in the year 2004. After nearly a decade GlaxoSmithKline decided to rework and make Horlicks ‘clinically proven brand’. They tied up with key pediatricians in India and conducted a clinical study in collaboration with national institute of nutrition, Hyderabad.
This study helped them to evaluate impact of Horlicks on growth and development in children. Five signs of growth like height, strength, healthy weight gain, blood health and concentration are now used by GSK in their claim of ‘Horlicks makes you stronger, sharper and smarter’.
What’s in store for customer engagement?
Life sciences companies are facing stricter compliances, increased competition and an urgent need to reduce “cost-to-serve.”
The Healthcare market is transitioning to a more consumer-centric model. Driving this change are the informed and price conscious patients. Increasingly, patients are becoming key partners in the design and delivery of care. Pharmaceutical giants are engaging patients for development of crowd sourced drug discovery platforms. Technology enabled real-time interactions can empower patients to design, manage, and deliver the kind of care they need—the way they want it, at their desired place and time.
According to Peter Drucker the aim of marketing is to know and understand the customer so well that the product or service fits him and sells itself. As the maturity of relationship between patients and the healthcare ecosystem evolves, involvement of patients would become a standard norm.
Today’s patient feels empowered by the easy access to the internet. A quick Google search and there’s tons of information for the patient to feast on. A Pew Research Center survey was conducted from March 7th to April 4th 2016 on 1,520 Americans with age 18 and older to measure how they cope with information demand in their lives and how they felt about the volume of information they counter. A whopping 81 percent felt confident in their ability to use the internet and keep up with information demands in their life while 79 percent felt that having a lot of information made them feel that they have more control over things in their life.(1)
The sheer volume of information on the internet can make its search overwhelming, difficult to navigate and validate. A simple query for health information can display thousands of sites thus making it difficult for people to discern whether the source of information is credible and trustworthy. A Pew Research Center survey found that people who seek health information on the internet don’t follow recommended guidelines for examining the reliability or timeliness of information. As a matter of fact, half the individuals reported checking the date and source of information only occasionally, hardly ever, or never.(2)
However, the objective of this article is not to look into how a patient can distinguish between relevant or irrelevant information, but to showcase why blogging could be an important factor as an effective medico-marketing and patient education tool.
A Brief History of Blogging
The term “blog” is short for ‘web log’. A blog is described as a discussion or informational board/page published on the internet and consisting of discrete entries known as posts. Over a period of time, the blog assumes the form of a series of articles (posts) created by a person, stored in chronological order that are searchable, and allow readers to share, like, dislike and/or comment on the created content.
In comparison to the elegant blogs that we come across daily, the earliest blogs didn’t bear any resemblance to the blogs that we see today. As a matter of fact, the term “blog” wasn’t coined until the late 1990s.
Before the concept of blogging became popular, digital communities took various forms such as Usenet (a worldwide distributed discussion system available on computers), commercial online services such as GEnie (General Electric Network for Information Exchange), BiX (Byte Information Exchange), the early CompuServe, email lists and Bulletin Board Systems (BBS – a computer server running software that allows users to connect to the system using a terminal program).(3,4)
Dave Winer is considered as one of the ‘fathers’ of blogging and is believed to have pioneered Web syndication techniques. On 7th of October, 1994 Dave published his first blog post. At that time, he named it Davenet. His blog Scripting News has been in existence since 1994 and is still present on the internet (www.scripting.com).(5,6) The emergence and growth of blogs in the late 1990s coincided with the advent of web publishing tools that facilitated the posting of content by non-technical users.
Justin Hall is another person who is widely acknowledged for creating the first blog ‘Links.net’ while he was a Swarthmore college student in 1994.7 However, the term ‘weblog’ wasn’t coined until the year 1997. Jorn Barger, editor of the influential early blog Robot Wisdom, is attributed with coining the term ‘weblog’ to describe the process of “logging the web” as he surfed.(8,9,10) Peter Merholz of Peterme.com abbreviated the term to “blog” in 1999.(5)
Ever wonder why is blogging such a craze?
A blog doesn’t require any prior technical knowledge. Server-based blogging software allows ordinary individuals to create engaging content in the form of blogs. Blogs are practical, low-cost vehicles that allow people with common interests to hold a conversation and share opinions. Most blogs provide a platform for blog visitors to directly engage with the author and interact with other individuals with shared experiences. It is an example of yet another ‘social software’ that supports the desire of individuals and organizations to be pulled into groups to achieve shared goals.
Pharma and Blogging: What’s the Connection?
Most people would cite ‘family’ and ‘health’ as two of the most valuable thoughts at the top of their mind. It is well documented that health problems are the most pressing issues in daily living. From chronic lifestyle health problems such as obesity, blood pressure and diabetes to acute health conditions such as cancer and cardiomyopathy, problems can be easily tackled/managed when healthcare stakeholders find a way to collaborate. While the pharmaceutical industry focuses on developing medicines, both doctors and patients need to access and use them effectively for them to have a positive impact on society. The true implications of collaboration can be judged by its impact in the real-world in daily life and not a clinical study setting.
Here’s where blogging helps bridge the divide. Blogging not only helps disseminate information but also stimulates a dialogue between various stakeholders within the pharmaceutical industry and the allied healthcare industry, including patients. Transcending geographical boundaries, pharma blogs can help build a web of connections all over the globe to encourage thought building and innovation.
While it will be too much of a leap to say that a humble blog could resolve pressing world health issues or could help in the immediate development of a new medicine, it will most certainly spur an idea or serve as a catalyst to help others build on it.
Running a blog provides pharmaceutical companies with an excellent platform to connect with end users (patients), educate them and create awareness of diseases, thus building brand credibility. Like any other print or digital publishing activities, blogging requires you to think from the consumer’s (patient’s) perspective, understand their interests, take current trends into account and invite other Key Opinion Leaders (KOLS) to share their insights on your blog. Blogging is not a single periodic campaign. It involves continuous engagement with patients and industry peers that is focused on current, relevant developments and shared interests.
Blogs provide three distinct technical advantages over websites.
Ease of updating text, video files (vlogging) and audio (podcasts) even from a hand-held device—mobile (moblogging).
Engages a larger audience through better search engine rankings. This is attributed to having highly engaging and informative content on the blog.
Cost of maintaining a blog. While generating interest and engaging a wider audience, maintaining a blog is a low-cost affair.
Blogging gives pharmaceutical companies the freedom to share information more frequently and adapt to current trends more easily than regular websites. Blogging can also be done in a controlled environment that can comply with pharma regulations wherever necessary. Pharmaceutical firms must invest time in conducting research to identify their target audience, locate information gaps within your target audience and find opportunities to fill in these gaps wherever information is inadequate or not readily available.
It should be borne in mind that pharmaceutical blogs also are subject to FDA regulations and guidelines for content as there are for any other pharmaceutical communications. Direct-to-consumer (DTC) compliance must be observed.
Considering these restrictions and strict regulatory oversight, pharmaceutical companies can opt for either branded or unbranded blogs.
Branded vs Unbranded Blogs
Here’s a simple difference between ‘branded’ and ‘unbranded’ content. Branded pharma sites will host the product’s name, indications and attributes. Unbranded pharma sites don’t. For example, Advair.com is the branded site for GSK while asthma.com is an unbranded site by GSK that focuses on asthma.
A Branded blog augments brand awareness. It positions the company as a campaigner in specific disease segments, increases search engine rankings (through search engine optimization – SEO for keyword phrases), and creates awareness in the target community about a specific disease state or product. Branded blogs provide information seekers with authentic information and allow influencers to share the content across online forums.
However, there is a flipside to branded blogs. Regulatory authorities such as the FDA mandate that such blogs carry Important Safety Information (ISI). While this is very important to provide balanced, scientific information, it can clutter and distract the reader. It may also reduce the reader’s trust because the site would appear as just another marketing avenue.
2. Unbranded Blogs
Unbranded blogs have fewer restrictions in the creation of content and can potentially add more value. Such blogs provide a platform for open discussion of a disease state, lifestyle conversation and empowering stories to share within the community. An unbranded blog is more authentic, unbranded storytelling that allows the organization’s voice to be heard, influences online sentiment and builds keyword traffic.
Here are six reasons why pharmaceutical companies should invest in creating unbranded blogs:
Educate patients, caregivers and healthcare professionals who are looking for information and updates on the disease.
Increase awareness of the disease and improve diagnosis.
Generate leads by registering patients/caregivers/healthcare professionals in a CRM database.
Engage patients and drive them to prescribers.
Good PR. It provides an excellent opportunity to support a cause or foster goodwill toward the brand.
Unbranded blogs don’t contain product claims which makes them less regulated and allows information to quickly connect with the market.
Here are a few examples of unbranded pharma blogs.
Blogs help build followers as they can be easily integrated with social media platforms like Twitter, Facebook, and Google+. Every post that is updated on a blog can trigger social media alerts and send alerts via email to its subscribers which can help increase web traffic.
A well-managed blog builds the reader’s confidence in you, your company and your brand. With increased consumer engagement, a strong connection is built with the reader that encourages them to return for more relevant information.
What role does the FDA play in regulating pharma blog content?
A draft guidance document — ‘Guidance for Industry – Fulfilling Regulatory Requirements for Post marketing Submissions of Interactive Promotional Media for Prescription Human and Animal Drugs and Biologics’ — was published by the FDA in 2014. The guidance states that a pharmaceutical firm is directly responsible for product promotional communications on sites that are owned, controlled, created, influenced, or operated by, or on behalf of, the firm. These promotional communications include firm-sponsored microblogs (e.g., Twitter), social networking sites (e.g., Facebook), firm blogs, and other sites that are under the control or influence of the firm. Irrespective of whether the firm is directly involved or has someone else acting on its behalf, FDA considers the firm responsible for the content on the blog as well as for submitting the blog to FDA to meet post marketing submission requirements.
Further, pharmaceutical firms need to show transparency in disclosing their involvement on a blog by clearly identifying user generated content and communications of its employees or third parties acting on behalf of the firm. A pharmaceutical firm can achieve this by including the firm’s identifier (name or logo) as part of the communication.
A firm is generally not responsible for user generated content that is truly independent of the firm (i.e., is not produced by, or on behalf of, or prompted by the firm in any particular manner.
Also, the FDA does not ordinarily view user generated content on firm-owned or firm-controlled venues such as blogs, message boards, and chat rooms as promotional content on behalf of the firm as long as the user has no affiliation with the firm and the firm had no influence on the user generated content.
From a few stand-alone blogs in 1994 to countless blogs created every day, blogging has come a long way. With growing engagement and increased ease of access to internet, blogging is proving to be a powerful tool to get the brand’s message across. The ease of sharing information within social communities and improvisation in uploading new content makes it relatively easy to generate engagement. This can, in turn boost your credibility and improve search engine rankings.
Blogging is no longer a hobby but a serious business tool that has and continues to attract major pharmaceutical firms. Its influence should not be underestimated. Pharma blogging has endless possibilities for today’s businesses and should play an important role as part of a sound marketing plan.
Wearable devices are increasingly becoming an integral part of healthcare and wellness industry. Pharmaceutical companies have moved beyond using wearable devices for clinical trials and apart from recording signs and symptoms, ensuring adherence to treatments too can be one of the important objectives. In commercial operations, the use of wearable devices can help drive sales. As a consequence, the pharmaceutical industry has seen increasing growth in partnerships between drug makers, technology companies and patient groups.
The use of wearables is going to shape the future of product sales and marketing. According to a report released by Transparency Market Research, a leading U.S. based market research and analysis firm, the global wearable technology market will make further gains at a CAGR (Compound Annual Growth Rate) of 40.8% from 2012 to 2018. The value of the global wearable technology market in 2018 is expected to be U.S. $5.8 billion, an increase of close to 800% on its 2012 value (U.S. $750 million).1
It is interesting to note that wearable technology is increasingly popular with youngsters. Nielsen, a leading global information & measurement company that provides market research, insights & data, states that nearly 48% of wearable owners are between the age group of 18 and 34 years.2
What Is Wearable Technology? Most people think of wearables as devices that are usually worn on the wrists, like a Fitbit that allow continuous monitoring as well as recording of basic health parameters such as number of steps or distance, calories burnt and heart rate. But in reality, wearable devices can and does include items such as glasses (Google Glass), jewelry and clothing worn on or around the body that incorporates sensors and associated electronic technologies.3
Also, wearables aren’t limited to counting steps or measuring the heartbeat. They are versatile devices that not only track a person’s activity levels but can also influence consumer behavior and even motivate them to make healthier lifestyle choices.4 In the disease management space, wearables can provide alerts for dosing times, monitor symptoms for chronic ailments and provide you with a customized fitness goal.
What Role Will Wearables Play In The Pharmaceutical Industry? As Brian Williams, director at PwC (PricewaterhouseCoopers) puts it, “Some biopharma companies are beginning to realize the potential ramifications to their business that wearables can bring, and they are starting to explore with pilots and new technologies”.
Companies are keenly tapping into technology to expedite the expansion or innovation of their business models to seize value beyond varied episodes of care. The aggregated data collected through wearables can bring value to both physicians and care providers. Insurance companies can collect important data and current health trends regarding medications and drug adherence from the data collected from patient wearables.
The disproportionate information that existed traditionally between the doctor and patient is collapsing with increased adoption of wearables. The introduction of these digital technologies is making the patient more engaged and responsible for his/her care and will bring immense value in terms of long-term disease management.
To take advantage of these opportunities, pharmaceutical companies have begun partnering with large and small technology developers since these digital tech innovators are driving the trend for wearables.
A case in point is the table below that lists a few pharma pioneers that have actively adopted wearable tech to design customized solutions for improved patient care.
Wearables and Apps
ViaOpta Nav App5
Apple iPhone and Android Mobile
Helps persons living with low vision increase mobility and regain independence.
Free download available App store in iTunes & Google Play
ViaOpta Daily App5
Apple iPhone and Android Mobile
Personal assistant to help people with low vision with their everyday activities.
Free download available App store in iTunes & Google Play
Apple iPhone and Android Mobile
The app provides a first-hand feel of what it is like to live with visual impairment.
Free download available App store in iTunes & Google Play
Inhaler device to treat COPD
Next generation inhaler that provides patients with real time access to their inhalation use.
Launch in 2019.
Vital Connect’s HealthPatch® MD 7
Used to continuously measure vital signs, electrocardiogram (ECG) data and activity levels.
Used in clinical trial setting in 2014.
ActiGraph’s wGT3X-BT Monitor 7
Johnson and Johnson Health and Wellness Solutions
Intelligent virtual coaching solutions built on Patient Athlete™ program8
iPad® or iPhone®
Holistic virtual coaching and rehabilitation solutions striving to transform the patient experience and healthcare delivery model.
Available in iStore.
Apple iPhone (iOS 8.2 or higher) and Android Mobile (Android 5 or higher)
A consumer-looking, but medical-quality smart watch that helps predict epileptic seizures and measures stress, activity and sleep.
Available for online purchase.
*Empatica is not a pharmaceutical company. But since they have developed a wearable that is of medical-quality, it has been included in this list.
The Future of Wearables Gadgets such as Google Glass exhibit great potential in diverse areas from surgery to telehealth. Many health care providers appreciate the idea of collecting and recording information over a period of time through a wearable device as this can provide them with a clearer picture of the patient’s health than a single test.
If I were to wear the thinking hat of Isaac Asimov, I can easily envision a future where patients walk into a drug store wearing their Google Glass and effortlessly check for dosage regimes, possible side effects and even get visual list of the medicines they need to purchase.
In times to come, a wearable won’t be merely a fun accessory, but rather a necessity and a healthy lifestyle choice. For example, the iTBraTM by Cyrcadia Health is a smart bra that is able to keep track of breast health.10 Similarly, the Leaf Healthcare Sensor (a wireless, single-use, disposable device that is adhered to a patient’s chest) can help prevent bedsores. The Leaf Sensor monitors the patient’s position, orientation, movement and activity. Care providers and physicians can remotely monitor the turning and mobility status for all patients through visual notifications.11
Advances in wearable technology will allow patients to seamlessly pass on health information to their doctors in real-time to discuss their condition and associated treatments. This can give a major boost to telemedicine by facilitating virtual appointments between patients and their health care providers.
Like companion diagnostics, people in the future could have companion wearables/ devices to accompany medicines. One example of this is the development of a match-stick sized mini-pump for the treatment of type 2 diabetes by Intarcia Therapeutics. This mini-pump (ITCA 650) can be placed subdermally in the patient once or twice a year for continual delivery of the diabetes treatment drug Exenatide. This has the potential to become the world’s first and only injection-free glucagon-like peptide-1 (GLP-1) agonist.12
Current Challenges with Using Wearables
While the number of people using fitness trackers is increasing, not everyone is tech savvy. There still appears to be some resistance among patients to engage with technology. Technology naive individuals may find it difficult to interpret or operate such digital tech. Consequently, wearable manufacturers would need to focus on making wearable usage as simple and the experience as engaging as possible.
Cost The cost of wearables plays a vital role in influencing their purchase decisions. Wearable manufacturers would need to keep costs at reasonable levels to influence usage by patients and fitness enthusiasts. An affordable wearable could directly impact its usage in government healthcare plans or pharma business models aimed at improving drug compliance, adoption, and adherence.
Battery-Life Most wearables that are available to the consumers have limited battery life. While there are a few wearables that have long-life batteries that need to be replaced after a year of use, a majority of the trackers need to be charged. For accurate real-time data collection, medical grade wearables must be capable of operating for prolonged periods without the need for frequent charging.
Privacy Calculating the return on investment (ROI) of wearable technology is a major challenge that most companies struggle with. However, ensuring data privacy and regulation of the data captured isn’t lagging too far behind.
Like with any other piece of technology, privacy and security are prime concerns with any wearable technology. Sensitive personal medical data will be transmitted wirelessly or via device applications to your personal mobile. Can the wearable be protected from malware and viruses? How can the data transmitted through wearables be made secure? These are some tough questions wearable manufacturers need to address.
FDA Approval for Medical Devices The FDA’s Center for Devices and Radiological Health takes keen interest in the advances and convergence of medical devices with connectivity and consumer technology. Does the wearable collect, analyze or share consumer information? Does the wearable diagnose or treat a specific disease of health condition? Patient data is personal information that needs to be protected. In order to safeguard patient data, certain laws have been set in place.
The data generated from the wearable may be subject to the following laws:
a) Health Insurance Portability and Accountability Act (HIPAA)
b) Federal Food, Drug and Cosmetic Act (FD&C Act)
c) Federal Trade Commission Act (FTC Act)
d) FTC’s Health Breach Notification Rule
In a draft guidance issued in July 2016, FDA said that it doesn’t plan to review low-risk “general wellness products”, such as wearables or sleep trackers. The FDA will not require general wellness products to comply with premarket and postmarket regulatory requirements.
As per the guidance document, general wellness products such as wearables are exempt as long as they “are intended for only general wellness use…and present a low risk to the safety of users and other persons.”
The FDA defines general wellness products to be those with:
1. an intended use that’s related to maintaining or encouraging a general state of health or a healthy activity; or,
2. an intended use that relates to the role of healthy lifestyle with helping to reduce the risk or impact of certain chronic diseases or conditions and where it is well understood and accepted that healthy lifestyle choices may play an important role in health outcomes for the disease or condition.
Sungmee Park, Jayaraman S. A transdisciplinary approach to wearables, big data and quality of life. Conf Proc IEEE Eng Med Biol Soc. 2014;2014:4155-8. doi: 10.1109/EMBC.2014.6944539. PubMed PMID: 25570907.
Piwek L, Ellis DA, Andrews S, Joinson A. The Rise of Consumer Health Wearables: Promises and Barriers. PLoS Medicine. 2016;13(2):e1001953. doi:10.1371/journal.pmed.1001953.
Is your pregnancy checklist missing something? A prenatal screening, might be!
A healthy baby is a happy baby. As parents, one would always want to ensure good health for their baby even before the baby is born. The best way to ensure good health of the baby, before it’s birth is by talking to your doctor or a genetic counsellor and taking up prenatal tests.
Out of the 50 babies that are born, one has some defect. That constitutes 2% of the total number of new born babies. The causes for these birth defects may be genetic i.e. passed on from parents or chromosomal or it may be due to exposure to environmental factors such as viral infections, drugs, or a medical condition affecting the mother. In some of the cases, there is no apparent cause.
Testing during pregnancy is optional and should be discussed with a doctor, or a genetic counsellor. Making a decision to have a test or not is always up to the couple. In general, there are two main types of prenatal tests – a screening test and a diagnostic test.
Many birth defects in infants can be identified early during the pregnancy through prenatal testing. Such tests are often recommended by a gynaecologist or sonologist. The recommendations can be based on family history, personal history or pregnancy history of the mother.
Screening tests are offered to all pregnant women irrespective of the personal medical or family history, and these results give an estimate of the probability that a baby has a health problem. Examples of screening tests are ultrasounds, non-invasive prenatal testing, first trimester screening, and second trimester screening. When a higher than usual risk is identified by a screening test, couples are often referred to a genetic counsellor or a clinical geneticist for a genetic consultation. The clinical geneticist or genetic counsellor helps the couple in the decision making process of whether or not to pursue diagnostic tests and supports them through the testing process.
During a genetic counselling session, the genetic counsellor helps the couple understand the intricacies of the identified risks and what it could result into. Details about how such conditions are diagnosed, strategies on how a family may cope with the risk of a genetic condition during pregnancy, are shared to help them to deal with the issues associated with a genetic condition after birth, should it be present in the baby.
Diagnostic tests provide accurate results and are always offered as a follow up to a screening test where a higher than moderate risk is identified for a certain genetic condition or anomalies are identified on ultrasound scan. These tests are conducted to confirm the diagnosis in the baby. Such tests may have associated risks in some cases. Examples of diagnostic tests include chorionic villus sampling (CVS) and amniocentesis.
The screening and diagnostic test reports are made available at the earliest possible that is within 2-4 weeks, depending on the type of test and considering the nature of urgency. The reports are handed to the couple by a genetic counsellor or a clinical geneticist who understands the report, and can help with the further course of action.
When a baby is found to have a problem before birth, the parents are given information about the health problem that has been identified. Depending on the stage of the pregnancy, a couple will be able to discuss options of planning for the birth of the baby or ending the pregnancy. Whether one decides to continue or end a pregnancy, support and information will be offered. Pregnancy can be terminated up to 20 weeks if the baby is diagnosed to have a genetic problem.
Although the doctor or genetic counsellor can never guarantee the birth of a healthy baby, couples often feel reassured about their assessed level of risk, and are likely to feel more confident in their decision-making about screening and testing options.
Although the mention of a prenatal test may be quite daunting, the benefits of undergoing screening can be reassuring and helpful. Talk to your doctor or genetic counsellor to learn more about prenatal testing options for yourself.
Some of the factors which increase the likelihood of a baby having health problems are:
The When the mother is in her mid-30s or older (not necessarily her first pregnancy)
Where there is a close relative or a previous child with a serious health problem
There has been exposure to some chemical or other environmental factors during the pregnancy
One or both parents of the baby has a health problem that may be passed on
One or both parents of the baby are known ‘carriers’ of a particular faulty gene
Where the parents are related by blood (e.g. first cousins)
A disease is considered to be ‘rare’ when it affects one in about 2,000 individuals in the population. There are anywhere between 5,000 to 8,000 diseases that are considered to be ‘rare diseases’ according to WHO statistics. Although individually rare, collectively, the incidence of rare diseases could be as high as 6-8% in certain populations. In developing countries like India, owing to the social structure, high birth rate and high degree of consanguinity, about half a million children are born every year with rare disorders.
Nearly 80% of rare diseases are considered to be genetic diseases, where due to mutation in a gene, the normal function of the protein (encoded by the gene) is lost or the protein acquires abnormal function (gain-of-function), which results in a disease. A multi-centric study on Indian population showed that the frequency of newborns with malformations, such as neural tube defects and musculoskeletal disorders were upto 2%, while other genetic conditions such as beta-thalassemia, metabolic disorders were as high as one in 2,500. One of the major reasons for referral to genetic centers is seen to be for reproductive genetics, comprising prenatal diagnosis, recurrent abortions, infertility, and even multiple congenital anomalies.
Conventional genetic testing for rare diseases focus mostly on testing or sequencing of single gene(s), followed by a deletion/duplication analysis by multiplex ligation-dependent probe amplification (MLPA). This sequential testing strategy performed in a reflex-testing mode is time consuming and expensive, and thus not ideal for a developing country like India. New advances in genomic technologies, such as multi-gene panels, based onNGS (next-generation sequencing) allows us to detect all types of mutations, including large deletions/duplications, thus allowing us to perform a comprehensive genetic testing in a cost-effective manner.
Multi-gene testing vs single gene testing
Suma (name changed), a 29-year-old woman from Hyderabad, was suffering from recurrent respiratory tract infections and was found to have chronic sinusitis and bronchiectasis. In addition, she also had infertility. Her brother, Raghu (name changed) had azoospermia and infertility. However, he did not have any significant respiratory symptoms. They were born of a consanguineous marriage.
Mutations in the gene namedCFTR (cystic fibrosis gene) have been linked to male infertility with or without respiratory symptoms. However, since Raghu’s genetic test results, done for known mutations in theCFTR gene, was negative, Suma was prescribed a ‘multi-gene’ test that could test several genes related to infertility, ‘primary ciliary dyskinesia’ (PCD) being one of them. This test resulted in the identification of a ‘disease-causing’ mutation in the DNAH5gene that is linked to PCD. Raghu was later tested for this mutation and was also found to harbour the same mutation.
Although a diagnosis could eventually be arrived at in this family, the time taken and the cost involved for the family is no doubt a burden, which can be eased with introduction of multi-gene testing. Here, absence of a mutation in the single gene tested can set an impression that the genetic cause has been ‘ruled out’, leaving the patient more anxious. It is thus imperative that in lieu of getting a right and timely diagnosis, multi-gene panel testing becomes a necessity. This can have an immense impact on the life of the patient.
A multi-gene panel testing is more a necessity than a choice, in order to make the right diagnosis, more so when the clinical indications are highly overlapping across various disease conditions.
In this case, known mutations in thecystic fibrosis gene(CFTR),were first tested owing to the higher frequency of these mutations across various populations. However, absence of mutation in the CFTR gene, did not exclude the possibility of a genetic cause, since the untested genes and regions were far higher than those tested.
With a family history of infertility and with no known mutations being detected in the CFTR gene in the patient, multi-gene testing was considered necessary to arrive at a confirmatory diagnosis. This led to the identification of a disease-causing mutation in the DNAH5 gene, thus, confirming diagnosis as ‘primary ciliary dyskinesia’ (PCD).
Although there are no therapeutic approaches available that can reverse the abnormality, a definitive diagnosis in this case can clearly benefit the patient by devising proper disease management and surveillance measures. There are proven reproductive technologies that can assist patients with PCD to undergo successive fertilization.
What lies ahead?
General awareness about genetic testing, and understanding the benefits of multi-gene testing by NGS over the single gene or mutation specific testing, can help both clinical practitioners and patients in making a right choice to arrive at a definitive and faster diagnosis.
Altogether, this case is just an example among numerous cases, where multi-gene based genetic test helped in diagnosis of a rare disease. It is about time for India to embrace NGS-based multi-gene approach for the routine genetic testing of rare disease, as it is highly sensitive, accurate, fast, and economically feasible.
Laser Vision Correction has grown significantly over time, due to increased safety and precision as well as increased consumer awareness and expanded approval of new technology and treatment modalities.
LASIK (laser in situ keratomileusis) continues to be the most widely used surgery for most ranges of refractive corrections. It is safe and visual recovery is rapid. It can be enhanced and combined with other procedures like Phakic IOLs, Intraocular lens implantation etc. With the addition of the wavefront technology, femtosecond (FS) laser, photoablation is able to create precise subsurface incisional planes. Scanning excimer lasers now allow for bigger and smoother ablation zones.
A world literature review of LASIK completed in 2008 showed an overall satisfaction rate of 95.4%, the most common reasons for dissatisfaction being residual refractive error, dry eyes, older age, and night vision symptoms.
Most LASIK complications can be corrected so that no long-term problems persist. However, some uncommon complications can have permanent visual consequences.
A realistic picture has to be given to the Patient by the Surgeon. The basic procedure and normal clinical course following the surgery like side effects (dry eye, glare and halo sensation) should be explained prior surgery. Possibilities of retreatment or additional treatments (10-20% cases), post operative need of glasses (in presbyopes) must be told to the patient.
LASIK is recommended at the age of 18-21 years. Up to -10 D or myopia (short sightedness) and +4D of hyperopia (long sightedness) and astigmatism up to 5 D can be corrected. A stable refraction is the first and foremost criteria.
LASIK is not recommended in patients with collagen vascular disease, autoimmune, or immunodeficiency diseases; women who are pregnant or nursing; patients with signs of keratoconus; and patients taking isotretinoin or amiodarone.
Other conditions with potential adverse outcomes include ophthalmic herpes simplex or herpes zoster, or other systemic diseases like diabetes mellitus, HIV. Patients who are active in martial arts, contact sports, should be informed that with LASIK there is a chance of flap injury. (Source; text book of cornea Jay. H. Krachmer)
Though, much as been said about LASIK, the first and foremost modality today and in the future will be spectacles only.
Both the patient and the doctor will be able to decide on laser vision correction only after the refractive error has been corrected by spectacles. As laser correction is recommended after the age of 18, spectacle use is inevitable till that age.
The advantage of spectacles is that they can be prescribed by an optometrist also where as laser correction requires a super specialist. The cost of spectacles is way cheaper. Spectacles can be changed as and when the power changes whereas laser correction is irreversible.
The use of spectacles may not be optimal in certain patients who have high refractive errors as the peripheral vision is constricted but they are the only means one can correct refractive errors in children. Spectacles today are a fashion statement and designer frames with celebrities promoting it make it the first choice in younger generations even in those who have no refractive error.
On Jan 30, 2013 while the country stood in silence as a mark of respect to the father of the nation on his 65th death anniversary, a gazette notification was passed which could have meant the death of good quality serious clinical research in India. It definitely meant the death of reasoning, the death of stakeholder engagement when after a year of deliberations and receiving suggestions from at least 32 organizations, they were summarily dismissed and not incorporated in the notification, which is now law. The ethical clinical research industry was faced with a Hobson’s choice, the necessity of accepting one of two or more equally objectionable alternatives. To continue doing clinical trials in the light of the gazette notification, means being not compliant to the law, because some of the provisions are difficult to implement. To stop doing clinical trials, both ongoing and in the future, would mean being morally unethical as it won’t be in patient and public interest.
The way I see it, good quality clinical research by the serious players will continue as patient and public interest is at the heart of what they do. They will soldier on in the interest of patients and the public. But they will not litigate. After all, public interest litigations (PILs) are filed not necessarily in the interest of the public. This industry believes in being industrious, hardworking, and committed to the unmet medical and clinical needs of the people who are eligible to be included in clinical trials so that they can serve an altruistic purpose of doing good for the larger community.
In the first place, let us understand that compensation is not applicable as a blanket provision in the world of good quality serious ethical clinical research as participants are fully informed, fully comprehend, and only then make a volitional decision to enter the trial. If they suffer from an adverse event related to this participation they are medically managed free of cost. Patients are insured and investigators are indemnified. Despite this, if there are reasonable and justifiable grounds for compensation, the same is done. Per section 2.4.7 of the Indian Good Clinical (Research) Practice (GCP) guidelines, if the clinical trial related injury is deemed related to the study or drug, and is endorsed by the ethics committee, the event is compensable and sponsors have compensated, although in many cases the patient’s relatives, investigators and ethics committee members have wondered why is the sponsor doing so when the patient was well looked after by the sponsor.
This notification may have been hastily passed perhaps as a knee jerk reaction to the Supreme Court diktat that either clinical trials need to be stopped or overseen by the Health Secretary to assure that participant rights, safety and wellbeing are monitored. The notification seems to have internal and external inconsistencies. Some provisions are not feasible to implement. For example, it is mentioned that from the day of serious adverse event (SAE) occurrence the sponsor and investigator need to report to the DCGI’s office within 24 hours and submit a detailed analysis of the same within 10 days. Often one comes to know of the event 10 days after occurrence. It is reported immediately but by this notification one is already non-compliant. Is the DCGI’s office geared for e reporting of SAEs? It should have been worded as from the day one comes to know of the SAE, not from the day of its occurrence. Changes to informed consent forms, contractual changes, getting fresh approvals both internally and from ethics committees will pose operational challenges which can even take as long as 6 to 12 months.
The notification states that medical management of any injury needs to be paid for, for an indefinite period, even if not related to the trial. For example, a participant while traveling to a clinical trial site, has a road accident, and will now need to be medically managed free of cost for the life of that patient. Such blanket provisions do not exist in any part of the world. Compensation for lack of efficacy or intended therapeutic benefit of the investigational product goes against the basics of clinical research. Sometimes patients do not respond even to approved and marketed products. Use of placebo is generally done as an add-on to current standard of care. Why should a sponsor have to compensate if there is wilful negligence or protocol violation on the part of the investigator? Sometimes patients are not compliant. The sponsor does select the investigator, trains him and his team, monitors and oversees the trial conduct with a clinical research associate, quality standards manager and auditor, plus the US FDA, EMEA and the Japanese MOH inspect some sites. Even if the DCGI’s office is unable to monitor, even if ethics committees don’t have the time to oversee, the industry does a very thorough job of monitoring and its standard operating procedures are stricter than any law of the land.
Wouldn’t such blanket compensation clauses promote research misconduct? Won’t patients be induced to participate in clinical trials? There is no clarity on how would one determine causality, and accordingly determine the amount of compensation, and the sponsor may not have the opportunity of representing to an independent arbitration committee. Having written this, I must also add that so far we have not received any frivolous claims for compensation and the Expert Committee has adjudicated in some cases that the SAE was not related to the study, in line with the causality assessment of the sponsor, ethics committee and investigator.
While the ethical research minded industry does support the mandate for compensation for clinical trial related injuries/death in the new compensation rules, and this step will further strengthen human subject/participation protection systems in clinical trials, the gazette notification if not suitably amended will be difficult to implement. Access to new medical innovations for unmet medical needs will become an issue as no new drugs may reach the Indian market. The research/innovation culture recently propagated by the government may take a back seat for academic (including investigator initiated) research and we would miss this golden R & D opportunity to build research capacity and capability.
Thankfully the sustained advocacy by the Indian Society for Clinical Research along with other like-minded bodies has resulted in an amendment to the gazette notification which hopefully should become law on June 12 this year. The contentious clauses alluded to above have been suitably amended. The same has been posted for public comments for 45 days.
I wish to end by writing that clinical trials don’t kill patients. Rather, if not for the clinical trial especially in oncology, many a patient would have died a premature death. Clinical trials are controlled and regulated to a much greater extent than clinical practice. Let’s be balanced and understand the benefit to risk ratio, maximizing benefit, minimizing risk and optimizing the therapeutic experience for the patient. Primum non nocere – at least do no harm.
Degenerative diseases are diseases remaining after the antibiotic victory over infectious diseases. The other important cause of injury and death is road accidents. The degenerative diseases are the result of cell death. Specialized cells meant to carry out special functions such as muscle or nerve die due to several reasons and are not replaced and this results in loss of function. The loss of function leads to the degenerative disease. A good example would be Parkinson’s disease. This disease is caused by death and degeneration of dopamine secreting neurons in the brain. Loss of dopamine secreting cells results in decreased levels of dopamine. Dopamine is needed for co-ordinated muscle movement. Parkinson patients show a characteristic tremor and inability to move their limbs and body in a coordinated manner. The present way to treat these patients is by giving -Dopa ,a precursor of Dopamine through an oral route. This is a very ineffective way of treating this disease and it invariably results in slow and painful death.
Though it was known that diseases involving the blood forming tissue, the bone marrow could be treated successfully by transplanting healthy bone marrow which was tissue matched , it was not known whether it could be extended to other tissues viz. brain. Bone marrow transplantations also showed that the successful cures were due to a special type of cell called stem cell which had the property of self renewal as well as differentiation into all the blood cell types.
It was in the last part of the 20th.century that Dr.Thompson from the University of Wisconsin, U,S.A. showed that the inner mass cells from the developing human embryo could be induced to act as stem cells with the potential to develop into each and every cell in the human body. He was not first to show this because it had already been shown in a mouse model. This discovery literally gave birth to regenerative medicine, since the stem cells could be used to regenerate cells lost due to death or decay. There was great hope for patients of Parkinson and other degenerative diseases. However, the hope was short-lived, since further research showed that the embryonic stem cell as they were called, had a great potential also to form tumors.
At this point, good news appeared in the bone marrow stem cell research. Patients who had undergone bone marrow transplantation for blood cell diseases showed that some of the stem cells had also given rise to tissues other than those of blood cell origin. This observation went against a well established dogma of developmental biology which stated that differentiation was a one way street and there was no going back i.e. stem cell from bone marrow had to give rise to blood cells and not to nerve or muscle.
Thus due to the dogma, adult tissue specific stem cells could not be used for regeneration of neurons, muscle or cartilage, even though experimental results showed otherwise. In the last ten years overwhelming evidence from clinical trials all over the world, including India have shown that tissue specific viz. bone marrow, adipose tissue and mesenchymal stem cells can and do regenerate muscle, cartilage, bone and neurons. The stem cell task force of the Indian Council of Medical Research the Government body which has to O.K ,the use of bone marrow for regeneration of cartilage etc.is still adamantly refusing to permit it except as an experimental therapy. Since the stem cells cannot be patented and only the process of enriching or cultivation is patentable resulting in very porous IPR which can easily be broken, no pharmaceutical or biotechnology company is willing to finance such trials. This has resulted in several doctors carrying out stem cell therapy without any documentation and validated SOPs. The nett result is fleecing of desperate patients. However, there are a few law abiding doctors and biotechnology companies who have carried out clinical trials and shown conclusively that regeneration of adult tissue is possible using adult tissue specific stem cells such as bone marrow. A large number of trials carried out in Japan, U.S.A and Europe also show the same results.
One of the first trials using autologous bone marrow enriched stem cells was for re-establishment of blood capillaries in Critical Limb Ischemia or Burger’s disease. Burger’s disease is a disease of tobacco smokers mainly India, Japan and south east Asia. Sufferers show loss of circulation in their lower limb due to narrowing of vessels and blood clotting. Loss of blood supply leads to cell death and resultant gangrene. The only way save these patients is amputation of the lower limb making these patients unable to make a living since, the patients are mostly laborers. In some cases a by-pass can be done to re-establish circulation and save the limbs. The trial conducted by Dr.K.R.Suresh, an eminent vascular surgeon at Sri Bhagwan Mahaveer Hospital, Bangalore, conclusively showed that revascularization was achieved in all most all patient’s of Burger Disease, when their own bone marrow enriched stem cells were injected into the muscles of their lower limb. The results were published in the Journal of Vascular Surgery.
These results were substantiated by another similar study by another vascular surgeon Dr.Vijaya Raghavan from Chennai. Several other studies in Japan also support these findings.
Another trial conducted in Delhi by Dr.A.P.S. Suri,Maxcare Hospital, Delhi, concerns treatment of diabetic foot ulcers using patient’s own bone marrow derived stem cells. Diabetic foot ulcer is very difficult to heal. This is because the blood vessels supplying blood to the ulcer area are destroyed and are not regenerated due to diabetes. No conventional treatment exists to treat these ulcers, which turn gangrenous, leading to amputation of the limb. In this study it was clearly shown that bone marrow stem cells can restore circulation and heal the ulcer. Several studies done abroad also support this finding.
A most promising trial to show that bone marrow / adipose tissue derived mesenchymal stem cells can regenerate the cartilage in the knee joint was conducted by Dr.Pradeep KIran,Columbia Asia Hospital, Bengaluru, in a sports injury. The results were very promising. This trial was followed by another trial by Dr.Rudraprasad and Dr. Deepak Rudrappa who showed that cartilage damage in Osteoarthritis could be reversed by bone marrow/adipose tissue derived mesenchymal cells in a large number of patients. These studies have been confirmed by laboratory studies which conclusively showed that mesenchymal stem cells from bone marrow/ adipose tissue could be differentiated into chondrocytes.
Mesenchymal stemcells are known to have immunomodulatory properties
Several studies in the United States of America has shown that these cells can be used to immunomodulate in clinical trials. A trial in New Delhi showed that mesenchymal stem cells could be successfully used to treat septic shock syndrome.A trial at Bangalore showed that mesenchymal stem cells can bring about decrease of RA factor in rheumatoid arthritis patients.
It is time now to convince the Government of India that Cellular Therapy is now ready to standard of care for several degenerative diseases listed above. There are several more such a Parkinson’s,stroke,multiple sclerosis ,alcohol induced liver damage and myocardial infarct where evidence is mounting from well trials abroad that bone marrow/adipose tissue derived stemcells can be a reliable tool for regenerative medicine. Unfortunately several other degenerative diseases cannot be treated as of now viz. Muscular Dystrophy, Chronic Kidney disease, Spinal cord injuries, since in these, degeneration is followed by SOS repair which makes it necessary to clear this scarification before stemcell implantation. Tissue Engineering approach is needed in treating some of the above listed diseases. Government funded institutions alone can carry out research and develop novel treatments involving the use of stemcells from bonemarrow/adipose tissue/umbilical cord /cord blood.
In conclusion, regeneration of lost or damaged adult tissues with specialized function such as muscle or neuron is possible with tissue specific stem cells viz. bone marrow/adipose tissue/cord blood. Conclusive evidence is available from well conducted clinical trials for Burger’s disease, diabetic foot ulcer, osteoarthritis and rheumatoid arthritis. Success in other degenerative diseases will soon follow.
1. Motukuru, Suresh K.R. et al, Therapeutic angiogenesis in Buerger’s disease, patients with critical limb Ischemia by autologus transplantation of bone marrow mononuclear cells. Journal of Vascular Surgery 48515-605-2008
Dr. A.P.S. Suri, Max Care Hospital, Delhi – Presentation of “ Innovation in Healing Diabetic Wound with autologus bone marrow stem cells” at STEM -2011 conference in Gurgaon, Delhi (NCR), India
2. Roberts Sally. Et al – Prospects of Stemcell Therapy in Osteoarthritis. Reference Medicine- 6351 – 366 – 2011.
Dr. Pradeep Kiran, MBBS,D’Ortho,DNB, MCH Sports Medicine(UK)and Dr. Rudrappa.MS – Presentation of “ Stemcell Therapy in Osteoarthritis” at the STEM – 2012, Hyderabad, India
Society for Regenerative Medicine &Tissue Engineering
Trustee, STEM FOUNDATION