WikiJournal Preprints/The Significance & Need of prioritizing Health Technology Assessment added with economic evaluations of medical interventions in Low & Middle Income countries (LMICs): The Covid-19 experience

Background
The term HTA & economic evaluation of medical intervention is quite unknown and rarely analysed while providing medical interventions in LMICs. HTA deals with examination of short and long term effects-consequence of application of medical interventions-technologies in various aspects such as societal, legal, economic, and ethical considerations. The key objective of HTA is to provide technology-policy alternatives to policy makers to make healthcare accessible, affordable and available to everyone. Historically HTA was developed in a systematic way beginning in the U.S. Office of Technology Assessment (OTA), which published its first report on the subject in 1976. Some historical notes about early development of HTA were published by the International Society of Technology Assessment in Health Care (ISTAHC) and the International Network of Agencies for Health Technology Assessment (INAHTA). The current ongoing covid-19 pandemic learning’s and the consequence of pandemic globally had clearly made us feel the need of an independent HTA ministry or a separate wing of health ministry to provide alternative cost effective interventions to save the people who can’t afford the costly interventions. Of course I am not talking about the propaganda based alternatives of natural healers etc who are selling and promoting products not having any scientific evidence backed by corrupt politicians and management people. In fact due to lack of proper HTA protocols and guidelines they are playing with lives of innocent people for sake of earning money in illegal and unscrupulous ways playing with their emotions. The main concern is that the LMICs have the greatest need of HTA to provide accessible, affordable, available healthcare because of limited options for making different choices. Despite the fact that most LMICs doesn’t have an active HTA program, it should be noted that evaluative work related to HTA is being carried out in LMICs by external agencies, some public health universities, few industry, European Union (EU), and WHO. The World Bank is also supporting HTA; earliest known work in HTA by the World Bank was in China during 1987 and 1988. WHO (world health organization) was involved and interested in HTA from the beginning of the process. The Declaration of Alma Ata on Primary Health Care in 1978 states (statement number-VI) that essential health care should be based on practical, scientifically sound methods and technologies made universally accessible to individuals and families in the community through their full participation and at a cost that the community and country can afford to maintain at every stage of their development in the spirit of self reliance and self-determination. The first meeting of the International Society for Technology Assessment in Health Care was held in 1985 with the cooperation of WHO Euro in its Copenhagen office ( ).

Understanding the Need of Health technology assessment, economic evaluation and evidence-based medicine
There is no perfect way to assess damages from the global COVID-19 coronavirus pandemic. There is widespread agreement among economists around the world that the impacts of covid-19 on the global economy will push a vast majority of population below poverty line (BPL). Early estimates predicated that the most major economies will lose at least 2.9 percent of their gross domestic product (GDP) over 2020 which was restated to a GDP loss of 4.5 percent. For better understanding perspective, global GDP was estimated at around 87.55 trillion U.S. dollars in 2019. The 4.5 percent drop in economic growth results in almost 3.94 trillion U.S. dollars of lost economic output.

'''HTA is a multidisciplinary process that uses explicit methods to determine the value of a health technology at different points in its lifecycle. The purpose is to inform decision-making in order to promote an equitable, efficient, and high-quality health system ( ).''' HTA is not limited to pharmaceuticals and devices, it incorporates every interventions used to improve health, prevent diseases, morbidity, mortality, diagnosis, treatment, risks as well in order to evaluate and provide with long-term care. It is also concerned with procedures of organization and supportive systems. HTA helps  policy makers in understanding and making good decisions by providing them with objective, transparent, and scientifically based-backed information in order to enhance the use of safe, better and acceptable interventions. Here we can simply analyse that oxygen supply is most essential if we want to use ventilators and at the same time oxygen alone can save life of many in the covid-19 pandemic as everyone knows that the most essential for saving patients of covid-19 was oxygen. At the same time it’s cheaper as compared to high cost of medicine used without scientific evidence in several countries. Hence it’s evident that the policy and management failed particularly in the case of India to provide enough oxygen supply which was a '''cost effective way to save lives. If there was a well established HTA ministry and cost effective analysis this can be stopped earlier.'''

In LMICs particularly the resources are limited and the healthcare demands are increasing with increasing global burden of diseases on the limited resources that are available. The covid-19 pandemics have put an extra demand on already overburdened and overstressed healthcare systems. The net result is burn out phenomenon taking lives of several people globally. The Policy & decision makers don’t have various choices for allocation of resources between different developmental needs based services and demand of covid-19 pandemic due to limited finite resources. Economic Evaluation helps policy makers of making choices based on the costs and consequences of alternative uses of resources and interventions.

Economic evaluations are measures of the effect of an intervention in relation to the resources it consumes. The Economic evaluations of health interventions are performed to support the best efficient use of limited resources. In LMICs like INDIA this will help policy and decision makers in the maximization of health benefits struggling with resource constraint. In economic evaluations, the incremental cost-effectiveness ratio (ICER) formula clearly shows the link with the medical part and the need for a critical assessment of all evidence. The outcomes are expressed in terminology life-years gained (LYG) or quality-adjusted life years (QALY) gained. QALY includes both quantity and quality of life (QoL). It is calculated by estimating the total life years (gained) from an intervention and weighting each time period within these life years with a quality-of-life score or utility. The two most important principles of a complete Economic Evaluation are:

A. the economic evaluation study must incorporate both the costs as well as the effects-outcomes of the programme being evaluated. B. the economic evaluation must compare between two or more alternative interventions. It’s important to note the fact that choice of alternatives in health care is not only dependent on the cost but also on the quality and quantity of outcomes generated by the alternatives. Hence we need to compare both the costs and consequences of the two or more alternatives that are under comparison.

An Economic Evaluation is expected to improve allocative & technical efficiency of resources. As per requirement there are various types of economic evaluations which can be done to know about output of interventions. The simplest cost-minimization analysis (CMA) analyses only costs when the alternative interventions have equal effects. This cannot be categorized as a full economic evaluation looking at both costs and effects of several alternatives. As an example we can compare the cost of oxygen concentrator versus oxygen cylinder. Cost effectiveness analyses is the first form of complete economic Evaluation fulfilling  both the criteria of comparing two or more interventions and incorporates both costs as well as effects. Here it’s important to differentiate that in all Economic Evaluations, the final result is presented as a ratio of Cost and Effects, with Cost in the numerator and Effects or Outcome in the denominator. The results are expressed in the form of net cost per health outcome. For example cost per covid-19 case prevented or cost per covid-19 case treated or cost per life saved. In (CEA) the output is expressed in life-years gained or a disease-specific outcome. CEA compares two or more interventions for net investment and health improvement in health‐care strategies competing for similar resources. CEA have evolved from disciplines of Economics, Decision Analysis and Operations Research. CEA can be utilized to decide on the best mode of treatment/intervention between different alternatives within a particular resource scenario. For example '''we may use CEA to compare between surgical treatment, medicinal therapy with different available drugs, and combination therapy for treating Mucormycosis if we are having a particular budget constraint. Another example, we can also use CEA to compare between different modes of delivery of covid-19 vaccines among different age groups through a hospital based programme or a community based programme.''' CEA cannot be utilized to compare between different health’s outcomes, e.g. we cannot use CEA to decide whether to use the available budget for treating patients with covid-19 or to provide HPV vaccines for adolescent girls to prevent cervical cancer as both have different health outcomes. CEA is a useful advocacy tool to bring attention of policy and decision makers to programs that have been ignored but cause significant mortality or morbidity or both. CEA results are presented in terms of ratios; the most commonly stated CE ratio is the Incremental Cost Effectiveness ratio (ICER). ICER is represented as: see figure2 (Cost of intervention – Cost of comparator)/ (Outcomes of intervention – Outcome of Comparator)

The interpretation of the ICER is dependent on the sign of the numerator and the denominator. There are four different combinations of possibilities when comparing the costs and the outcomes of the intervention and the comparator. They are:

I. The new intervention may be more costly and more effective than the comparator

II. The new intervention may be less costly and more effective than the comparator

III. The new intervention may be less costly and less effective than the comparator.

IV. The new intervention may be more costly and less effective than the comparator

The difference in costs and effects when plotted on a graph is referred to as the cost effectiveness plane

In another form of economic evaluation called cost-utility analyses (CUA) preferences are taken into account and outcomes are expressed in extra costs per QALY gained. Sometimes it may be difficult to translate a variety of outcomes in LY or QALYs. In such cases cost-consequences analyses (CCA) is performed separately presenting incremental costs and these various outcomes. In a cost-benefit analysis (CBA) which is another form of economic evaluation, a monetary value is given to the benefits. However, because of difficulties of translating outcomes in monetary values, this approach is usually not applied by health economists. It is preferable to express results in extra costs per LY and QALY gained since impact on mortality and morbidity are eventually the most important outcomes for patients and these outcomes allow comparisons of results across indications. This is very difficult if disease-specific outcomes are applied. For example, how is a policy maker going to compare the extra costs to avoid a cardiac event versus avoiding a Mucormycosis in a covid-19 patient? The importance of measuring the effect on costs, mortality and/or quality of life should already been taking into account when setting up study protocols.

A full economic evaluation can be represented graphically with a cost-effectiveness plane (CE-plane, Figure 2). This shows the cost difference (Y-axis) and effect difference (X-axis) between an intervention and its comparator. The comparator can be no intervention, the current situation or a relevant cost-effective alternative intervention for the same condition.

Implications
The COVID-19 pandemic has overstressed already overburdened underdeveloped healthcare systems of LMICs as well as global health systems. This is going to produce a long-term shift in priorities across all countries. In addition, the considerable financial burden of dealing with the pandemic will mean healthcare budgets will be even more constrained. The field of HTA will remain ignored looking clinical treatment on priority basis. A lower willingness to allocate budget for HTA due to COVID-19 will likely lead to greater financial loss due to lesser knowledge of better alternatives.

Recommendation
LMICs must prioritize HTA agencies/departments in order to get the best results from the limited resources and budget of healthcare. Early and continued engagement with HTA bodies will provide useful insights into solving future problems related to healthcare needs. The early stage incorporation of HTA and regulatory bodies in the form of integrated scientific advice will be very beneficial; it may be invaluable during this period of growing uncertainty. The use and development of HTA in LMICs will open new vista to alternative and innovative arrangements, and provide benefit across the local health ecosystem. All stakeholders and decision makers should have a complex analysis, planning, and engagement at a local level and national level to apply HTA for benefit of the population.

Conclusion
The covid-19 pandemic learning’s focus on the fact that HTA must have strong political support in LMICs due to the fact that resources for health care are limited and need to be assessed to reduce economic burden. Hence, choices must be made, and rational choices need to be backed by scientific evidence. The use of evidence based scientifically sound health services well assessed by HTA and for cost effectiveness should be an essential element in modern health care policy, administrative, and clinical care. The policy makers should be aware of comparative effectiveness of different interventions before taking decision for implementation of any policy research. One of the major challenges for HTA is to bridge the gap between evidence and health policy and practices. This can be solved to a greater extent by holding decision makers accountable and responsible for making use of evidence for application of health interventions. This will also reduce corrupt practices to a great extent in LMICs. In LMICs like India economic considerations are in fact the prime element in the decision-making process. The other important factors are willingness/ability-to-pay (e.g. economic crisis, unmet medical need, lobby, etc.) and policy makers may sometimes not just wish to maximize health (in LY or QALYs) and give more weight to other criteria. The LMICs must give priority to HTA and economic evaluation because resources are finite which in long run get depleted and endanger the accessibility, availability and quality of the health care system. Performing an economic evaluation is not cutting and rationing of healthcare. It’s there to support doing things as much as possible in right way with our limited resources for the total population. Medical/health intervention is of prime importance and economic evaluations provide scientific evidence whether an intervention also offers value for money.

For policy & decision makers, it is not easy to use economic arguments for refusing cost of a medical intervention, especially when these interventions are recommended and needed. HTA is of utmost importance to convince policy makers of the evidence to make a health care system with a high accessibility, availability, affordability as well as highest quality as possible and which is durable in the long term. HTA illustrates not only benefits, but also costs and opportunity costs; into account is certainly an ethical way to make best choices in healthcare.

Declaration
-This paper has not been previously published and is not currently under consideration by another journal. The document is Microsoft word with English (United States) language & 3077 words Total.

- Ethics approval and consent to participate: Not applicable. This study has not involved any human or animals in real or for experiments.

-Consent for publication: Not applicable

-Availability of data and materials: The data & materials for study are available as reference.

-Conflicts of Interest/ Competing Interest: There are no conflicts / competing of interest

- Funding-Self sponsored. No aid taken from individual or agency etc.

- Authors' contributions: The whole work is solely done by the Author - Dr Piyush Kumar, M.B.B.S. - Sri Krishna Medical College, EMOC- General Medical Officer- Bihar Health Services- Government of Bihar, India.

- Acknowledgements- I am thankful to Advocate Anupama my wife and daughters Aathmika and Atheeva for cooperation.

- Author information: The author is currently working as general medical officer for the government of Bihar.

-Financial Support & sponsorship: Nil

'''The article preprint is also submitted as preprint to various preprint server and preprint is having doi as well as searchable on various search engine. The article is not published in any peer reviewed journal.'''

Acknowledgements
I am thankful to Advocate Anupama my wife and daughters Aathmika and Atheeva for cooperation.

Competing interests
There are no conflicts / competing of interest

Ethics statement
Not applicable. This study has not involved any human or animals in real or for experiments.