The Rampant Use of Nutraceuticals in Nepal: A Growing Concern

In recent years, the popularity of nutraceuticals products derived from food sources that offer health benefits beyond basic nutrition has surged in Nepal. These products, which include vitamins, minerals and herbal supplements promise a wide range of health benefits, from boosting immunity to improving cognitive function. However, the unregulated influx of these products into the Nepalese market raises significant concerns regarding consumer safety and product efficacy.

Lack of National Regulation

Current director general of Department of Drugs Administration (DDA) had recently confessed on national newspaper that there is no regulation guideline on national level for the nutraceuticals' in Nepal, which on my personal opinion is the most pressing issue. As we know that pharmaceuticals are strictly regulated in the country via laws and bylaws but nutraceuticals fall into a grey area in terms of regulation. This lack of regulation means that there are no standardized guidelines for the import, manufacturing, or sale of these products. Consequently, the market is flooded with a variety of nutraceuticals, many of which have not been adequately tested for safety or effectiveness. Despite being well regulated by the national entity, standards of medicines being consumed by Nepalese population is worrisome, context of nutraceuticals is beyond imagination. 

The Influx of Imported Products 

Due to the absence of local regulations, Nepal has become a lucrative market for imported nutraceuticals. Products from countries with varying regulatory standards are readily available, often without proper labeling or quality assurance. Specifically, majority of Nepalese market is flooded with nutraceuticals manufactured in India and imported by local agents. We are not sure of regulations and monitoring status within India as numerous accusations are widespread on international news regarding safety concerns of products regulated by government of India. Condition might be further troublesome in Nepal as most of the imported products are not even registered in India. This situation is exacerbated by aggressive marketing strategies that tout these products as cure-alls for various health issues, leading to widespread use among the Nepalese population.

Misuse of Social Medial 

Social media platforms like Facebook ads have become hotbeds for exaggerated advertisements and false claims regarding nutraceuticals, preying on the vulnerabilities of consumers seeking quick health fixes. Influencers and marketers exploit the lack of regulation to promote these products with sensational promises of miraculous benefits, often without any scientific backing. This rampant misinformation, amplified by viral marketing tactics, misleads the public into purchasing and using products that may be ineffective or even harmful, further complicating the challenge of ensuring consumer safety in Nepal's burgeoning nutraceutical market.

Renowned Medical Professionals Prescribing Haphazardly 

Alarmingly, even some renowned names in the medical field are prescribing nutraceuticals haphazardly. This practice not only undermines the credibility of the medical profession but also places patients at risk. When trusted healthcare providers endorse these unregulated products, it gives a false sense of security to consumers, who may then use these supplements indiscriminately. The underlying reason as per my opinion is handsome amount of money being offered by the nutraceutical agents to the medical professionals on each prescription. 

Challenges in products Consistency 

Another significant issue is the difficulty in obtaining the exact same brand of product consistently. Unlike pharmaceuticals, nutraceuticals do not have generic equivalents, making it challenging for consumers to maintain a steady regimen. This inconsistency can lead to varying results and potential health risks due to differences in product formulation and quality.

Issues with Ayurveda and Alternative Medicines

The problem extends beyond nutraceuticals to Ayurveda and other alternative medicines marketed as health and immunity boosters. While these traditional practices were not initially in the mainstream, the haphazard prescription of nutraceuticals by medical doctors has normalized the use of such products. This shift has further complicated the landscape, making it difficult for consumers to distinguish between effective treatments and unproven remedies.

Solutions and Way Forward: 

1. Establishing Regulatory Standards: The government should develop and enforce comprehensive regulations for nutraceuticals. This includes setting quality standards, requiring proper labeling, and ensuring that all products are tested for safety and efficacy before they reach the market.

2. Educating Healthcare Providers: Medical professionals need to be better educated about the potential risks and benefits of nutraceuticals. Encouraging evidence-based prescribing practices will help ensure that patients receive safe and effective treatments.

3. Implementing Import Controls: Stricter import controls are essential to prevent the influx of substandard or unsafe nutraceuticals from abroad. This can be achieved by requiring importers to provide documentation proving that their products meet Nepalese regulatory standards.

4. Consumer Awareness Campaigns: Launching nationwide awareness campaigns to educate consumers about the potential risks associated with unregulated nutraceuticals. Providing clear information about how to choose safe and effective products will empower consumers to make informed decisions.

5. Promoting Research and Development: Encouraging local research and development of nutraceuticals can help ensure that these products are tailored to the specific health needs of the Nepalese population and meet high safety and efficacy standards.

Conclusion: 

The unregulated use of nutraceuticals in Nepal is a growing concern that demands immediate attention. Without proper regulation, the health and safety of consumers remain at risk. It is crucial for policymakers to develop and enforce guidelines that ensure the quality and efficacy of these products. By doing so, Nepal can protect its citizens and ensure that the benefits of nutraceuticals are realized without compromising public health

What are your thoughts on the current state of nutraceuticals in Nepal? Share your experiences and suggestions in the comments below. Let's work together to advocate for a safer, healthier market.

Hypocrisy of Modern Medicine : Example from Nepal

Have you ever pondered over the medications prescribed during your visits to a healthcare provider in Nepal? Did you pause to question the necessity, safety, and efficacy of those medications? If not, you might have either experienced exceptional care or fallen victim to the systemic inadequacies plaguing modern medicine in the country. Despite being touted as evidence-based, the reality is starkly different – there exists a glaring absence of locally generated evidence to guide the approval and marketing of allopathic medicines.

One glaring truth encapsulates the essence of medical practice in Nepal: "Not a single allopathic medicine prescribed in the country has undergone rigorous clinical trials to scrutinize its safety and efficacy." This revelation might initially evoke disbelief or skepticism, but it underscores a fundamental flaw in the healthcare landscape. Medical practice operates on the assumption that if a medication is available in the market and outlined in textbooks, it must be authentic. However, the suitability of these medications and treatment protocols for the Nepalese population remains uncertain. Moreover, the irony intensifies when medicines developed overseas does not even undergo trials on Nepalese population but makes direct entry in the Nepalese pharma market legally endorsed by country

 

A closer examination of Nepal's medical framework reveals a complex network of hospitals and healthcare centers scattered across the country. From central to provincial and local levels, healthcare facilities cater to the diverse healthcare needs of the populace. However, the reliance on allopathic medicine as the cornerstone of modern healthcare is juxtaposed against the backdrop of alternative medicine systems such as Ayurveda, Homeopathy, and Naturopathy. Despite being labeled as evidence-based, the monopoly of allopathic medicine is not without its shortcomings.

Pharmaceutical companies operating within Nepal often resort to reassembling active pharmaceutical ingredients (APIs) sourced from other countries, primarily India. Consequently, the majority of medicines labeled as "manufactured in Nepal" are, in reality, repackaged or replicated versions of Indian products. This reliance on external sources for medication underscores the absence of indigenous research and development capabilities within the Nepalese pharmaceutical industry.

The absence of a dedicated research and development infrastructure within domestic pharmaceutical companies severely hampers the possibility of conducting clinical trials within the country. Consequently, Nepal remains reliant on medications whose safety and efficacy have been established primarily in foreign contexts. This systemic inadequacy not only compromises patient care but also perpetuates a cycle of dependency on external pharmaceutical markets.

The implications of this paradox extend beyond individual patient encounters to encompass broader public health outcomes. Without locally generated evidence to inform medical decision-making, healthcare providers are left navigating a landscape fraught with uncertainty. Moreover, the reliance on imported medications limits the country's capacity for innovation and self-sufficiency in healthcare delivery.

Addressing the hypocrisy of modern medicine in Nepal requires a multifaceted approach encompassing policy reform, investment in research and development infrastructure, and greater transparency within the pharmaceutical industry. Collaborative efforts between government agencies, healthcare professionals, and pharmaceutical stakeholders are imperative to facilitate the generation of locally relevant evidence and enhance the quality of patient care.

In conclusion, the paradox of modern medicine in Nepal underscores the urgent need for systemic reforms to align healthcare practices with evidence-based principles. By addressing the underlying deficiencies in clinical research infrastructure and promoting indigenous pharmaceutical innovation, Nepal can aspire towards a healthcare system that prioritizes the well-being of its citizens. Only through collective action and unwavering commitment to transparency and accountability can the country overcome the hypocrisy that pervades its medical landscape.

Challenges and Opportunities of Clinical Research In Nepal : A Closer Look

Clinical research plays a crucial role in advancing medical knowledge, developing new treatments, and improving patient care. While numerous countries around the world have established a robust culture of clinical research, Nepal is yet to make significant progress in this area. In this blog post, we will delve into the factors that have hindered the development of a thriving clinical research culture in Nepal and explore potential opportunities for growth

The Landscape of Clinical Trials in Nepal

Nepal has been involved in a number of clinical trials; however, it has primarily served as a research subject rather than actively contributing to the design and execution of trials. Most trials are initiated elsewhere, leaving Nepal to participate and provide data as required by the sponsor. This raises questions about the country's role in clinical trials and its ability to leverage research for its own benefit.

Reasons For Lack of Progress 

1. Absence of Investigational Medicinal Products (IMPs): A significant factor inhibiting Nepal's progress in clinical research is the absence of its own investigational medicinal products or devices. Currently, clinical trials are conducted for products developed by external entities, limiting the potential benefits for Nepal. By developing its own IMPs and successfully conducting clinical trials on them, Nepal could harness economic benefits and contribute to its own scientific advancement. 

2. Inadequate Resources and Infrastructures: Clinical trials demand a dedicated workforce and suitable facilities. Nepal faces challenges in terms of both human resources and infrastructure. Well-trained clinical research personnel are essential to maintain protocol adherence and ensure data quality. Currently, there is a lack of organizations offering clinical research training and certification courses, contributing to the suboptimal structure of clinical research activities.

3. Regulatory Framework: The regulatory framework for clinical research in Nepal involves the Nepal Health Research Council (NHRC) and the Department of Drug Administration (DDA). Both of these organizations work in collaboration to control regulatory as well as ethical aspects of clinical trials respectively. However, in reality, both of these organizations are not clear and concise on their own roles and responsibilities and hence are functioning without any solid guiding documents underneath. Since any of the clinical trials are not well monitored / inspected from the governmental authority, the quality of the data hence produced is solely dependent on the integrity of the researchers. 

Opportunities For Growth

1. Developing Own IMPs - Nepal has the potential to embark on the journey of developing its own investigational medicinal products and medical devices. This would involve investment in research and development, fostering collaboration between academia and industry, and aligning efforts with the country's healthcare priorities. 

2. Building Skilled Workforce: Establishing dedicated organizations or courses for clinical research training can bridge the skills gap. A workforce equipped with the necessary knowledge and expertise will ensure the integrity of trials, adherence to protocols, and accurate data collection.

3. Enhancing Regulatory Clarity:  Refining the regulatory processes and guidelines can attract more sponsors and researchers to consider Nepal for clinical trials. Clear and efficient regulations inspire confidence among stakeholders and expedite the initiation and execution of trials.

Conclusion

While Nepal may currently face challenges in establishing a vibrant culture of clinical research, there are significant opportunities for growth and progress. By addressing the identified hurdles and leveraging its strengths, Nepal can transition from being a passive participant in clinical trials to an active contributor, fostering its own scientific and economic development. With focused efforts, collaboration, and strategic planning, Nepal can pave the way for a promising future in clinical research

Disparities on Out of Pocket Expenditure In Nepal - Seed of Social Injustice

When it comes to seeking medical care, one cannot ignore the financial aspect. Have you ever wondered if the amount you paid for healthcare services was truly justifiable for what you received? The disparity in healthcare costs between hospitals often leaves us questioning the fairness of the expenses incurred. In this blog post, we delve into the world of out-of-pocket expenditure and the factors that contribute to the variance in costs between hospitals.

Understanding Out-of-Pocket Expenditure

Out of Pocket (OOP) expenditure is the portion of medical cost that individuals pay directly from their own income or through debt, excluding contributions from insurance or social security. It's a crucial metric that sheds light on the affordability and fairness of healthcare services. Imagine visiting two different hospitals for similar health issues and discovering a significant difference in costs. This raises the question of whether the price gap is equitable given the services provided and the severity of the condition.

Factors Influencing Out-of-Pocket Expenditure

1. Care Providers Cost: The initial ticket cost charged by hospital can vary greatly. This charge often reflects the hospital's internal expenses, equipment quality, and staff availability. Higher charges might correlate with more advanced services, allowing patients to choose according to their financial capacity and medical needs

2. Inpatient Admission Cost: The cost of staying overnight in the hospital various services can vary significantly. This disparity can make sophisticated hospitals seem unaffordable to many.

3. Diagnostic Tests: The cost of the diagnostic test can be a major component of OOP expenditure. In some cases, excessive tests are ordered, inflating costs unnecessarily.

4. Medicine Import: Nepal's reliance on imported medicines increases their cost due to import expenses. A local manufacturing approach could alleviate this burden and reduce overall healthcare costs.

5. Insurance and Social Security: The absence of robust health insurance and social security schemes in Nepal contributes to high OOP expenditure. Strengthening these systems can greatly alleviate the financial burden on patients.

Tackling the Issues: Solutions and Pathways Forward

1. Enhancing Insurance Coverage: Effective implementation of health insurance can significantly reduce OOP expenditure, providing a lifeline out of the poverty trap. This might involve digitalization, private sector partnerships, and other innovative approaches.

2. Hospital Grading and Cost Transparency: Grading hospitals based on facilities and services, and disclosing standardized costs for each category, can empower patients to make informed choices and level the playing field.

3. Income Based Payment: Integrating annual income data into healthcare  records can guide patients towards suitable healthcare options, especially beneficial for those with limited education.

4. Domestic Medicine Production: Manufacturing essential medicines locally can alleviate costs until robust insurance and digital healthcare systems are established.

5. Stringent Regulation and Ethical Practice: Monitoring hospitals and enforcing ethical practices are essential steps. Implementing reward and punishment mechanisms can shift the healthcare industry toward a patient-centric model.

6. Commitment to Ethical Practice: Ethical responsibility lies with healthcare practitioners, providers, patients, and the pharmaceutical industry. Ethical practices are pivotal in ensuring the healthcare system's benefits are maximized for all.

Conclusion 

Navigating the labyrinth of healthcare cost requires a collective effort from regulatory bodies, hospitals, healthcare professionals, and patients. The journey toward justifiable healthcare expenses involves reimagining insurance systems, fostering transparency, and promoting ethical practices. By addressing the factors contributing to high OOP expenditure and implementing innovative solutions, Nepal can move closer to a healthcare system where costs reflect the value of services rendered, without leaving individuals burdened by financial strain

                                                                                                      Thank You !!!

Clinical Trials on Rare Disease - Challenges and Opportunity

 Orphan Drug Development

Clinical trials conducted on any rare diseases that are intended for the marketing and approval of a new drug candidate for the purpose of establishing future novel therapy is known as orphan drug development. Orphan drugs trials are always of high importance in scientific community as these are tough to conduct in terms of regulation, Pharmacoeconomics, trials design and implementation. Since there are only a very few rare diseases trials being conducted, all the stakeholders intend to squeeze out maximum benefits from the trial.

As per the United States foods, drugs and cosmetic acts, rare diseases are such disease or conditions which impacts less than 200,000 peoples residing in the United States. Similarly, in European Union, a disease is considered to be rare if it affects one person out of 2000 citizens. There have been more than 6000 rare disease discovered so far affecting approximately around 3.5 to 5.9 % of worlds population. Most of rare disease have genetic origin (72%) and hence are difficult to treat with medication.  

Why Clinical trials on rare disease is difficult? 

1. Understanding Disease mechanics : There is very little understanding of disease mechanisms and pathophysiology of any rare disease which makes it impossible for a new therapy to establish inference on intervention and the outcome.

2. Genetic Variability: Since majority of rare disease have genetic predisposition, clinical manifestation for each of them will be different and drug effective for one type of genetic makeup may not be the best option for another group with different genetics. This specially makes clinical trials more complicated. 

3. Too less events: Though significant number of people are affected with various rare disease throughout the world, there are too few people available for a single clinical trial as the patient pool for each diseases under trial is always lesser than required for the enrollment. 

4. Adolescent predominance: Since most of the rare diseases are manifestoed in early childhood and adolescence, it is difficult to conduct trial on children and people with younger age due to legal and ethical issues. Also the rate of compliance to the clinical trial protocol is still very low. 

5. Statistical Insufficiency: Currently applied outcome measures are not appropriate for rare disease and reliability of newer methods is ambiguous. For example, smaller effect size etc. 

6. Pharmacoeconomic Reasons: Since clinical trials are very costly, if return on investment for any trial is seemingly low, pharmaceutical industry is less likely to invest their money for the good of society and science only. In comparison to other conventional trials and their outcome in the world, conducting clinical trials with inherently very low success rate is nto good idea for commercially oriented pharmaceutical companies and considering their return on investment, it is less likely to invest. 

Current number on  Rare Diseases Trials 

While putting keyword 'Rare Disease Trials', a total of 564 studies are popped out in clinicaltrials.gov, , out of which only 91 studies are currently recruiting participants whereas 342 have been already completed. Rest of the studies are either 'not yet recruiting' or ' suspended' from the process. 

Opportunities and Way Forward 

1. Noncommercial research activities. Unlike other clinical trials on a pharmaceutical product, there are very limited chances of trials getting successful on receiving license for market, sponsors may not be much interested taking such a challenge. Only a researcher organization with multiple collaboration should conduct such trials overlooking cost - benefit analysis of such research projects. 

2. Lenient regulatory obligations: if we apply the same regulatory framework with similar degree of scrutiny in rare diseases trial as we don in other exploratory / pragmatic clinical trials, there are chances of any such trial not to meet regulatory requirements. Hence, right from the pre trial implementation documents, rare disease trials should are conducted with much less of scrutiny and legal system are made easier so that such studies are promoted in the scientific era as well. 

                                                  Thank You !!!

Exploring Diverse Avenues of Income for Clinical Researchers

In the ever-evolving landscape of professional opportunities, the dream of earning from multiple sources has become a reality for a fortunate few. Clinical research, a field known for its dynamism, opens doors to an array of income streams that can be harnessed based on educational background, skill set, and experiences. Leveraging online platforms has further broadened the horizons for clinical researchers, enabling them to tap into various opportunities despite constraints.

Unveiling Lucrative Avenues

Medical Writing: Medical writing is a versatile domain that offers an array of roles. From drafting research proposals, summaries of product characteristics (SMPCs), safety reports, to crafting content for medical journals, health magazines, or websites, the opportunities are diverse. Clinical researchers can venture into protocol writing, investigator's brochures, informed consent forms, and trial reports. Flexibility is key here; one can be employed full-time, on a contract basis, or as a consultant, optimizing their skills and time while working from the comfort of their own space.

Data Management: Clinical data management, a pivotal aspect of clinical trials, presents an array of roles. Proficiency in basic data handling tools such as Excel and SPSS is essential. More complex trials may necessitate skills in software like SAS and R. Clinical researchers adept at working with data can engage in data entry, cleaning, and analysis, optimizing their contribution to the research process.

Phase I Clinical Trials: Phase I trials, involving healthy volunteers, offer an opportunity for clinical researchers seeking unconventional working hours. With stringent monitoring requirements, these trials often require staffing around the clock. For those with daytime commitments, engaging in phase I trials during mornings, evenings, or night shifts can prove to be a lucrative option.

Registry Involvement: With a solid foundation in research methodology, data management, and medical terminology, clinical researchers can expand their horizons by participating in disease registries and clinical trial databases. Playing a vital role in registering trials and maintaining databases, these experts facilitate both sponsors and registry platforms. Engaging with disease-specific or global registries can open doors to consistent income streams.

Project Set Up: Setting up project environments and managing clinical trial sites require a unique set of skills. Clinical researchers familiar with study site dynamics and experienced in project setup can contribute significantly. Handling logistical aspects, regulatory compliance, and site management, these professionals ensure smooth trial operations. With expertise, they can juggle multiple trials simultaneously, enhancing their earning potential.

Consulting Services: Providing consulting services to sponsors and Contract Research Organizations (CROs) offers a pathway to diversified income. Assisting foreign sponsors in navigating local environments for global trials or aiding pharmaceutical companies in pharmacovigilance post-product launch, clinical researchers can capitalize on their expertise and offer invaluable insights.

Conclusion: Embracing a Multifaceted Future

Clinical research professionals possess a unique skill set that allows them to explore a range of income-generating opportunities. As the field evolves and globalizes, the potential for diverse roles only expands. Embracing digital platforms and leveraging specialized skills can empower clinical researchers to seize multiple streams of income, transforming their professional journey into one of both financial stability and personal fulfillment.

So, whether you're a seasoned clinical researcher or an aspiring one, the world of clinical research is brimming with income-generating prospects. By aligning your expertise with the right opportunity, you can craft a rewarding and multifaceted career in this dynamic field.

Thank you for reading!

Urgent Need of Contract Research Organization (CRO) in Nepal

Nepal is currently facing a huge shortage of job opportunity leading to an incremental brain drainage from the country. All the faculties of educations are victims of this problem and same is the situation for clinical researchers and pharmacist. Working in the field of clinical research needs multiple expertise like sound knowledge of diseases, available treatment / therapies, research methodology, biostatistics, clinical operations and many more technical information along with organizational culture and teamwork skills. A well-functioning CRO can provide job opportunity and career growth platform to exercise all of these aspects for a clinical research aspirant. 

Let us understand first about how a CRO functions in a brief. A CRO always conducts research for other companies on a contract basis. Any pharmaceutical or biomedical or biotechnology based medical device company will prepare their product by performing drug development and early phase research. A CRO will take their product and perform clinical trial leading to regulatory approval of that particular candidate so that it can go to the market at the earliest.  

Why Nepal Needs a CRO?

There are many reasons why such organization should be established as soon as possible. I have enlisted few of them below: 

1. Creating more job opportunities:

There is extreme lack of job opportunity for various medical professionals such as doctors, nurses, pharmacist and other auxiliary health professionals despite good competency on the subject matter. A contract Research Organization is definitely a good platform for all of the professionals in terms of experience as well as financial return. 

2. Performing BPO: 

Since CRO works in the contract basis with other pharma or biotechnological organization, they can outsource any or all of their work anywhere in the world based upon the need by business process outsourcing (BPO) method; companies do not have to conduct research in Nepal by itself, but they can outsource the work from other countries to here in Nepal and pay as per the work on need basis. Suh work can be performed from home as well as office, which means it is an opportunity for a working professional to earn their extra income and also for people who want to work remotely from anywhere from the country. 

3. Opportunity to conduct large - scaled trials in the country

A CRO not only works on the basis of business process outsourcing (BPO), but also conduct research / trials on its own. In Nepal, we have enough hospitals and healthcare professionals but till date all the clinical trials that are being conducted are designed in some other countries and we are working just as data collectors. In future, if any vaccine candidates have to go through clinical trials, we can take up their product and conduct clinical trial on our own environment. Necessary skilled human resources will be produced from the corporations with enough of exposure on their respective fields.

4. Positive Impact on the country's economy: 

Since we are on or below poverty line as per economic parameters and running out of foreign currency reserve due to very wide trade deficit, a large-scaled companies running within the country and bringing money into the economy from outside world is of utmost importance for the economy to function better. Quantitatively if a CRO functions well in the Nepal, government can benefit directly from taxation and bringing foreign currency into the Nepalese economy. But on wider view, positive impacts are much more and qualitative in nature. These can be listed in terms of payment scale, lifestyle, work culture, exposure and skills enhancement, personal development, fostering local businesses, tourism enhancement and for creating positive environment within the country so that upcoming generations can see their future in their own country. 

If you also have some ideas to share regarding this topic, please feel free to comment below

                                                                                        

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Advancing Clinical Research in Nepal: Urgent Calls for Regulatory Framework Upgrades

In recent days, Nepal has been involved in a number of clinical trials specially after the hit of COVID-19 pandemic. Most of such trials were developed on some other countries, imported and implemented here in Nepal. Rise of COVID-19 has certainly given an opportunity for a burning mind of the country in order to involve in a global movement of developing a new therapy or vaccine. This movement has been facilitated from two major government organization - Nepal Health Research Council (NHRC) and Department of Drug Administration (DDA). But In order to make country self-dependent on developing and implementing new trials, there must be few upgrades in the regulation and infrastructure in both of these organizations. 

Nepal Health Research Council (NHRC) provides both ethical review support for all the trials registered and also acts as implementation body for any new trial conducted by or in collaboration with other organizations. In 2019, NHRC has published 'National Ethical Guideline for Health Research in Nepal' which provides direction to perform clinical trial activities anywhere within the country in the most ethical manner possible. All in one, NHRC works as regulatory body as well as implementation body combinedly. for this purpose, it has made collaborations with many national and international organizations working in the field of human health research such as Indian Council of Medical Research (ICMR), International Vaccine Institute (IVI), Oxford University Clinical Research Unit (OUCRU). 

Similarly, Department of Drugs Administration (DDA) is the national licensing authority of the country which reviews and authenticate the documents submitted by clinical trialist / individual or an institute. Based upon the favorable opinion and round of reviews, it provides certificate for conducting research. DDA approval is needed only if you are conducting trial / research on a specific drug or medications but not for other kind of therapies or observational research. After submitting documents physically to 'Administration' section, it will move to the respective department and reviewal process will start. There are multiple departments within DDA for different activities like registration of pharmaceutical company, a pharmacy, import / export of drugs, approval / registration of a medicine, registration of trial etc. 

Problems and Immediate Changes Needed in DDA 

• A new researcher coming to DDA in order to register his / her trial will demotivated by too many windows to queue, lots of Paperworks, ambiguous comments and lack of clarity among the review members themselves. But actually, review process is much simpler than it seems to be. In short, if review and approval process is made via online platform, all the activities will run smoothly in less time-consuming manner which will ease the whole process itself. Though DDA is the national regulatory authority where national as well as international delegates come for different purpose, DDA functions like any other government offices which should be changed immediately. Adapting online platform is mandatory for any office sooner or later. If appropriate arrangements are made in place needed to implement online registration, reviewal and approval process, research activities will be completed more smoothly. 

• Guideline and regulations should be updated enough to make them relevant with the time. Most of the legal obligation under which we are working currently are older than researcher themselves. Getting an approval and being regulated from those outdated guideline is another frustrating experience for a researcher. As for example, if you register a clinical trial which is adaptive in design, once the trial is approved and implemented, there might be multiple amendments to the protocol based upon current scenarios and the requirements. It is not possible to receive new approval license from DDA each time with the protocol amendment. DDA does not have such regulations in place to regulate such trials whereas adaptive design is the most commonly employed model of clinical trial throughout the world on recent times. Similar experiences are there with trials being conducted on emergency health situations like COVID-19 pandemics. 
• Other changes also carry some importance such as administrative, infrastructure wise and for smooth experience of visitors. Such arrangements may not directly affect much the integrity of the functions of DDA. 

                Immediate Changes Needed at Nepal Health Research Council (NHRC)  

Being a part of organization, I may be biased on reviewing functioning of Nepal Health Research Council (NHRC). If you are an independent researcher or have acquainted with the functions of NHRC from any other organizations, your review and experience will matter more than that of mine. Anyway, these are the changes that 'NHRC' should address at the earliest in order to foster research culture in Nepal. 

• Establishing an independent clinical research unit. A separate unit which is completely dedicated for reviewing new clinical trials proposals, conducting meetings and conferences with other different organizations for collaborations, continuation and daily implementation of the trials on the implementation phase and for capacity building of the clinical trials experts in the country. Such unit should be led by an expert working in relevant field. For clinical trial culture to foster in the country, it demands a lot of discussions, trainings and implementation. NHRC only can and should provide such platform for all the researcher working inside and out of the country. 
• Separating ethical review support from routine activities of NHRC. Since NHRC is working both as ethical review board as well as trial implementation body, there is chances of conflict of interest and functions of one can be hindered by the other. Ethical review board of NHRC should be independent not only on provision but also in physical and real sense. Ethical Review Board (ERB) and its activities must be independent from routine NHRC functions which includes multiple meetings, implementation of an observational trials, training and so on. All those activities will definitely hinder the ERB functions and international communities may not consider its activities with higher integrity. 
• Developing an online central information system. If any researcher working here in Nepal or any part of the world wants to make an query about the current situation of health research status or particular evidence, NHRC should be able to respond them online and such system has to be established available for public domain. All in all, NHRC should function as center of evidence generation and dissemination. 
• Strengthening research activities on other institutes. NHRC cannot and should not function all the health research activities on its own. Only if every medical college and hospitals of Nepal involve in evidence generation by themselves, research culture of the country will be upgraded. NHRC should be center of facilitation for other research institutes as well. 

If you have any other viewpoints about how research and clinical trials should be regulated / promoted in the country, please give your opinion on the comment box below.

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PRECIS Tool - Critical Analysis to Pragmatic Trials

https://www.bmj.com/content/350/bmj.h2147

Pragmatic Explanatory Continuum Indicator    Summary (PRECIS) is the tool designed by clinical trials specialist in order to help other clinical trialist to design a trial that best fits on pragmatic platform. Since most of the pragmatic trials being implemented in the recent days are self-declared, their design and implementation may not best fit with the global standard set for conducting pragmatic trials. Here we will discuss about the PRECIS-2 tool and its different domains. 

History of PRECIS tool 

The original PRECIS tool was developed in 2005 - 2008 by 25 international trialists and methodologists with the prime objectives of helping other trial specialists to make their better decision while designing a trial by allowing them to test the questions they are seeking answer for. PRECIS tool was used widespread between 2009 to 2013 by various researchers. Later this tool received a lot of criticism for having unclear face validity, inter rater reliability, the lack of scoring system, redundancy in PRECIS domain etc. After addressing all of those criticism and comments, an updated version was released in 2013 with the name of PRECIS-2 tool. This updated version is still being used globally and been cited around 1100 times from https://www.bmj.com/content/350/bmj.h2147 as per Sep 2022. 

Domains of PRECIS-2 Tool 

There are nine different domains in the PRECIS-2 tool which help trialist to think of the trials design decision considering the future reproducibility of the trial result. 

     1. Eligibility

• Are Participants recruited in the trials similar to the future intended population? 
• Higher the similarity between the people in trials and those in usual care settings, higher the score would be. 
• Excluding people with less adherence to treatment, based on laboratory tests results, having less responsive to the treatment, excluding people who have difficulties in completion of trials like old, aged population and children 
• If Inclusion / Exclusion criteria is more stringent by including many laboratory tests before drug administration, trial will incline towards explanatory design from pragmatic one. 
• Highest score that trial will get from this criterial would be Five. 

     2. Recruitment

• Was there the similarity of effort being made to recruit participant with that for a patient to engage into the treatment process? 
• In an extremely pragmatic settings, patient will be informed of the study in usual care settings and recruitment will be made based upon their interest. 
• Sometimes an extra effort needs to be made by additional human resources or by enhancing knowledge about the trial among potential participants via different communication tools such as mailing invitations letters, Radio / Television advertisement etc. The only concern is potential participants should not be over influenced by the information provided.
• Recruitment from usual hospital settings without additional effort is scored as '5'. 

     3. Settings

• How similar / different is the trial settings from usual care?
• In this domain, trialists are encouraged to match their settings proposed for a clinical trial with the hospital setting where patients are being treated on regular basis. 
• While designing a pragmatic trial, various characteristics of a settings are to be considered such as: geography, healthcare system, socioeconomic and cultural background of that particular country / community and other nuances of the population trial is being intended to apply on. Higher the matching between them, trial will be considered more pragmatic. 
• Sometimes the same socioeconomic constrains of a particular setting can be of no issue rather supportive in different settings. 

     4. Organization

• How different are the resources, provide expertise and the organization of delivery in the intervention arm of the trial from those available in the usual care settings. 
• This domain specifically focuses on resources and human expertise available in a particular healthcare setting. If service provided to a trial participant is from highly skilled and trained personnel in well-equipped setting but regular visitors are not receiving the same degree of care and treatment from healthcare center, trial will lose its pragmatism and will incline towards being an explanatory. 
• A highly pragmatic trial will receive score '5' and highly explanatory one will receive score of '1'

     5. Flexibility (Delivery) 

• How flexibly intervention is being administered in trial setting than usual care setting. 
• In order to make a trial more pragmatic, trialist should anticipate the future of that particular intervention post trial in the same hospital / study site and the flexibility on how to introduce an intervention should be provided accordingly.
• If protocol does not dictate rigidly how to deliver an intervention for a trial participant, there will be similarity in the between patient admitted and treated in the hospital and the trial participants. The most flexible study will score maximum of '5' which means trial is most pragmatic. 
• If trialist wants study to be descriptive in nature, he should be very rigid about dose, time-schedule, person and method of delivery of that particular intervention. But this methodology will score the trial least in this PRECIS-2 score system. 

     6. Flexibility (Adherence) 

• This domain check if the protocol adherence and monitoring techniques are compatible with the real-life scenario or not. 
• Encouragement to take intervention in its defined dose and time is mandatory both in clinical trial as well as clinical practice. But physician can only encourage and convince patient about the adherence to the treatment in usual care settings but in clinical trial there might be need of monitoring tools to be applied just to verify that adherence to treatment is ensured.  
• If trialist apply monitoring tools for protocol adherence to treatment, trial will be inclined to explanatory and will score close to '0' in PRECIS-2 tool. Whereas, if there involve only the instructions and encouragement from researcher / physician for trial participants without applying any monitoring tools, that study will score close to '5' in PRECIS-2 tool. 
• Monitoring tools may include pre-screening evaluation of adherence, withdrawal of participants based upon cut-off value of intervention adherence, scheduling discussions and repeated questioning to study team etc. this approach leads study to be descriptive from pragmatic. 

     7. Follow Ups 

• This domain focus on the how different are the follow ups procedure set by trialist from that being practiced at the hospital / site on routine usual care settings. 
• If the trial is very pragmatic, there won't be any scheduled follow up for participant after being discharged. But measuring an outcome of an intervention may be difficult if it could not be derived from electronic means, medical records and registries. Those trials which have no or minimal follow ups and no additional information to be collected during follow ups are considered to be more pragmatic trials. Such trials tend to score close to '5' as per PRECIS-2 tools. 
• In explanatory trials like blinded study of vaccine candidates, there would be frequent scheduled follow ups, follow up visits may affect primary outcomes and there would be extensive study of various biological markers from blood and other samples. 

    8. Primary Outcomes

• This domain emphasizes if primary outcome expected from clinical trial is directly relevant to participant or not
• While designing the pragmatic trial, outcome set by the trial should solve the problem of the people attributed from disease or condition being studied. For example, if a trial aims to reduce mortality from disease, its primary outcome should be the number of death events among enrolled participants in the defined time period. Same applies if primary outcome is based upon biological marker or a surrogate marker. 
• In the best-case scenario, the drug or a therapy used in pragmatic trial in particular sites will be the standard of care in future globally. Those trials with an obvious importance to the participants, score highest (close to '5') in PRECIS - 2 whereas studies whose outcomes are not the part of routine care scores lowest. Such trials are considered to be more explanatory than pragmatic.

    9. Primary Analysis

• This domain typically considers if all the data generated via trials are being considered during analysis phase or not
• Almost all the pragmatic trials use Intention-to-treat analysis model where all the participants enrolled into the trial are equally considerable for statistical data analysis regardless of whether they received full treatment, meet the primary outcome or loss to follow up. Intention-to-treat model typically follows 'Once Randomized, Always Analyzed' hypothesis which provides them very high reproducibility than per protocol analysis trials. 
• It is not possible for all the trials to follow Intention-to-treat model, where they will consider only those data which has reached data integrity benchmark as set by the protocol for statistical data analysis. Such trials are considered to be explanatory which serves the propose of being high specificity when used in the mass scale. For example, during the time of COVID-19 pandemics, therapy trials followed pragmatic approach and vaccine trials majorly followed explanatory models. 

When should the PRECIS - 2 Tool Be Applied? 

Keeping it simple, PRECIS - 2 tool is designed for trialist to be implemented while developing the trial protocol. All the domains of tools are applicable only when there is sufficient room to anticipate the future scenario of usual care post trial and implement the study protocol accordingly. But sometimes, for knowledge purpose, PRECIS - 2 tool can be applied for those trials which are already in implementation phase. Findings from such studies can be inculcate by making an amendment to the protocol if study allows adaptive clinical trial design. 

How to Use PRECIS - 2 Tool? 

Trialist can visit and register their trial from official website of PRECIS - https://www.precis-2.org/. After receiving confirmatory email response from university of Aberdeen, they can move forward to follow the scoring system. 

   

      Thanks!!!

 

About Monkeypox Outbreak : All You Need To Know

On 23 July 2022 World Health Organization (WHO) has declared Monkeypox as global health emergency quoting the report released from second meeting of International Health Regulation (IHR). This declaration was based considering the views of committee members, advisors and reports of multi-country outbreak. In response different countries has alerted their respective health authorities to get prepared for yet another public health challenge. Since India recently has reported increasing new cases and death event of Monkeypox victim, Nepal is also at risk of this disease outbreak if not able to take effective action early on. As an initiative, WHO representative has recently handed PCR test kits required for Monkeypox diagnosis to National Public Health Laboratory (NPHL) Nepal. This effort officially initiated in-house capacity development for disease surveillance, case identification and containment activities which should be strengthen enough to sustain and take control over future outbreak.

Brief History Of Monkypox Outbreak

Caused by Orthopoxvirus, monkeypox - supposed to be shy on human has reported its first case against human on 1970 from Democratic Republic of Congo. Firstly identified in 1958 from laboratory Monkey, Monkeypox has two distinct genotypes - Congo Basin and West African. The First outbreak was noticed in these two geographic regions only with animal to human transmission as primary source of infection and human to human transfer as the disease further spread. Outside Africa, Monkeypox was reported in United States by 2003 in dogs which rapidly infected people of midwestern states such as Wisconsin, Indiana, Illinois, Kansas, Missouri and Ohio. With extensive diagnostic, isolation and treatment facility, US was able to contain the virus within a month of spread. After a long gap of 15 years, United Kingdom reported four cases of Monkeypox on human beings by 2018 from people who moved to UK from Nigeria. With rapid public health responses, UK also contained the virus. Similarly, such small incidents were being identified and subsided in various other countries like US, Israel, Singapore and Benin within 2018 to 2021. 

Unfortunately on recent outbreak started from UK, world has miserably failed to contain the spread of virus and it is taking its toll globally and spreading further. First cases of west African strain was identified on 6 May 2022, followed by six more such events within a week. As per High Consequences Infectious Disease (HCID) network, total of 1735 cases were already reported by mid July, most of which are centered around London. Virus has made its way throughout the Europe, America and our close neighbor India as well. 

Clinical Progression of Monkeypox Infection

• For initial 10 - 12 days, there is an incubation period 
• Prodromal symptoms of headache, fever, malaise, weakness etc. 
• Lymphadenopathy: Localized or general swelling of lymph nodes is the distinguishing clinical presentation of monkeypox from other infections
• Rashes develop very soon which further progress to well formed lesion. Initial macular rashes develops to papules, vesicles and pustules. Monekypox lesion are well circumscribed, deep and umblicated (a dot like pattern is noted on the top). 
• Lesions generally confined to facial, anorectal and genital regions, 
• Generally 2 - 4 weeks of infection, the pustules get crusted and scabbed over and the illness resolves. 

Monkeypox has distinct clinical features from viruses of similar kind Chickenpox and Smallpox. Chickenpox is much more contagious, rashes appeared in a wave fashion and get subsided by  two weeks. Smallpox mimics monkeypox to maximum degree but thankfully timely development of vaccine has eradicated it by 1980 already. 

Is Monkeypox More Prominent in LGBTQ community ? 

Recent report from WHO has suggested that 98 % of the monkeypox cases  outside Africa are reported in gay men. This fact has spread a message of LGBTQ community being targeted disease population which can be misleading and help disease to spread further. In fact, spread of disease is dependent on people's behavior, basic health practice and hygiene not the sexual orientation. Monkeypox can be transmitted by close personal contact which includes - direct skin to skin contact, contact with body fluids, touching infected objects used by victims such as towel, beddings and clothes; respiratory contact also helps in easy transmission of disease. Also infected mother transmit the disease to fetus as monkeypox virus can cross placental barrier. It implies that any kind of close physical intimacy is attributable to disease spread. Reason behind predominance of reports from gay and bisexual community may be their confined communication and intimacy among their own community and poor health / hygiene practice. In fact, LGBTQ is highly susceptible to other infections also where disease  transmission is directly linked with sexual contact.

Is Monkeypox  changing its disease pattern ? 

Recently on 1st of August 2022, India has reported its first death case of monkeypox. A 22 years young male was tested positive on 19 July in UAE, but he travelled to India and later developed fever and swelling  and admitted to hospital at Kerala state. Though patient was having lymphadenopathy and fever, there were no lesions noticed throughout stay. Patient's overall health status quickly deteriorated and succumbed to death. As per the autopsy report, cause of death was unconfirmed and other justifiable underlying medical illness were absent, cause of death was attributed to monkeypox.  Though World Health Organization (WHO) has officially labeled the disease as moderate public health risk, reported case fatality are  in increasingly trend. Comparing the classical clinical presentation with the recent deaths reported from India, Brazil and Spain, all death events seems to be unanticipated. Here, Clinical presentation of monkeypox are more or less similar but susceptibility of the victims to other various infections increased significantly after getting infected with monkeypox. This phenomenon is further augmented by underlying chronic illness. Since there are no new reported mutated variants, disease pattern of virus is still unchanged. 

Treatment and Prevention

• Medicines: As per the Food and Drug Administration (FDA), there are no approved treatment specific for monkeypox virus. However, treatment of smallpox and cytomegalovirus also works for Monekypox as well. A drug candidate named "Tecovirimat" has shown some promising results from animal studies but scant is known about it's effectiveness in human; further clinical trials are under the way. Other potential treatment candidates include VIGIV, cidofovir, Brincidofovir, for which also extensive effectiveness data is yet to come. 

• Vaccination: Pre-exposure prophylaxis in the form of vaccination is the currently available most effective way of disease prevention. For various reasons, Center for Disease Control and Prevention (CDC) has suggested only high risk personnel such as laboratory workers be get vaccinated against Orthopoxviruses which is effective against Smallpox as well as Monkeypox. Routine immunization for all health workers is not a current recommendation. The two FDA licensed vaccine candidates are JYNNEOS and ACAM2000. The former is to be taken in two dosage 28 days apart and later one in single dose. 

• Public Health Measures: Active surveillance, investigation and contact tracing is mandatory to prevent human to human transmission by rapidly identifying, isolation and treatment of infected individuals and halt the speed of new transmission. Along with these measures since transmission of monkeypox is somewhat similar to COVID-19 (not in intensity), common public health measures are also similar. Routine healthy practice includes avoiding unnecessary public gathering, wearing mask in public places, washing hands frequently, avoiding unhealthy sexual behaviors and avoiding pregnancy by suspected women. 

Is There A Chance of Monkeypox Pandemic ?

Considering all the reported information about the natural history of disease, Monkeypox can affect human life significantly by becoming a major public health concern for a particular point of time at its worst but resulting into pandemic is far beyond from its ability. There are many attributable factors needed to create pandemic such as rate of disease spread, mode of disease transmission, incubation period of disease, clinical severity, effectiveness of available treatment options and preparedness of health facility in different countries. Monkeypox stands with feeble strength in all these aspects. Firstly, transmission potential of Monkeypox is far more slower and weaker than any other pandemic we have witnessed (like smallpox, COVID-19 etc); in order to transmit disease, relatively longer close physical contact is needed which itself limits rapid spread of disease. Also clinical severity of the disease is very less since there is no systemic involvement of the virus, which makes death due to Monkeypox virus alone extremely unlikely. Also, if we suffice the availability of smallpox vaccine before the disease take over and make use of all the strengthened (and already sensitized) healthcare system and augment it little further, existing healthcare facility can easily withstand burden of this disease. 

Monkeypox will be a big burden only if respected health authority of the countries fail to implement common public health guideline suggested by experts. 

Thank You !!!

References: 

1. https://www.nepalitimes.com/banner/big-story-of-small-pox-in-nepal/

2. https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html#:~:text=Persons%20with%20monkeypox%20will%20develop,lymphadenopathy%20(swollen%20lymph%20nodes).

3. https://www.bbc.com/news/world-asia-india-62344928

4. https://www.bmj.com/content/378/bmj-2022-072410

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157091/#:~:text=Between%20September%202017%20and%2031,region%20of%20Nigeria%20%5B16%5D.

6. India reports Asia's first monkeypox-related death; exact cause unconfirmed | The Times of Israel

7. https://www.who.int/southeastasia/news/detail/24-07-2022-enhance-surveillance--public-health-measures-for-monkeypox--who