The swine flu vaccination program has implications for the current pandemic preparedness. In 1976, 2 recruits at Fort Dix, New Jersey, had an influenzalike illness. Isolates of virus taken from them included A/New Jersey/76 (Hsw1n1), a strain similar to the virus believed at the time to be the cause of the 1918 pandemic, commonly known as swine flu. Serologic studies at Fort Dix suggested that >200 soldiers had been infected and that person-to-person transmission had occurred. We review the process by which these events led to the public health decision to mass-vaccinate the American public against the virus and the subsequent events that led to the program's cancellation. Observations of policy and implementation success and failures are presented that could help guide decisions regarding avian influenza. Kilbourne, New York Times, February 13, 1976  in Atlanta isolates of virus from recruits at Fort Dix, New Jersey, who had influenzalike illnesses. Most of the isolates were identified as A/Victoria/75 (H3N2), the contemporary epidemic strain. Two of the isolates, however, were not typeable in that laboratory. On February 10, additional isolates were sent and identified in CDC laboratories as A/New Jersey/76 (Hsw1N1), similar to the virus of the 1918 pandemic and better known as "swine flu."A meeting of representatives of the military, the National Institute of Health, the Food and Drug Administration (FDA), and the State of New Jersey Department of Health was quickly convened on Saturday, February 14, 1976. Plans of action included heightened surveillance in and around Fort Dix, investigation of the ill recruits to determine if contact with pigs had occurred, and serologic testing of recruits to determine if spread had occurred at Fort Dix.Surveillance activities at Fort Dix gave no indication that recruits had contact with pigs. Surveillance in the surrounding communities found influenza caused by the current strain of influenza, A/Victoria, but no additional cases of swine flu. Serologic testing at Fort Dix indicated that person-to-person transmission had occurred in >200 recruits  reviewed the findings. The committee concluded that with a new strain (the H1N1 New Jersey strain) that could be transmitted from person to person, a pandemic was a possibility. Specifically, the following facts were of concern: 1) persons <50 years of age had no antibodies to this new strain; 2) a current interpandemic strain (A/Victoria) of influenza was widely circulating; 3) this early detection of an outbreak caused by A/New Jersey/76/Hsw1N1 (H1N1) provided an opportunity to produce a vaccine since there was sufficient time between the initial isolates and the advent of an expected influenza season to produce vaccine. In the past when a new pandemic strain had been identified, there had not been enough time to manufacture vaccine on any large scale; 4) influenza vaccines had been used for years with demonstrated safety and efficacy when the currently circulating vaccine strain was incorporated; 5) the military vaccine formulation for years had included H1N1, an indication that production was possible, and no documented adverse effects had been described.ACIP recommended that an immunization program be launched to prevent the effects of a possible pandemic. One ACIP member summarized the consensus by stating "If we believe in prevention, we have no alternative but to offer and urge the immunization of the population." One ACIP member expressed the view that the vaccine should be stockpiled, not given.Making this decision carried an unusual urgency. The pharmaceutical industry had just finished manufacture of the vaccine to be used in the 1976–1977 influenza season. At that time, influenza vaccine was produced in fertilized hen's eggs from special flocks of hens. Roosters used for fertilizing the hens were still available; if they were slaughtered, as was customary, the industry could not resume production for several months.On March 13, an action memo was presented to the Secretary of the Department of Health Education and Welfare (DHEW). It outlined the problem and presented 4 alternative courses of action. First was "business as usual," with the marketplace prevailing and the assumption that a pandemic might not occur. The second was a recommendation that the federal government embark on a major program to immunize a highly susceptible population. As a reason to adopt this plan of action, the memo stated that "the Administration can tolerate unnecessary health expenditures better than unnecessary death and illness if a pandemic should occur." The third proposed course of action was a minimal response, in which the federal government would contract for sufficient vaccine to provide for traditional federal beneficiaries—military personnel, Native Americans, and Medicare-eligible persons. The fourth alternative was a program that would represent an exclusively federal response without involvement of the states.The proposal recommended by the director of CDC was the second course, namely, for the federal government to contract with private pharmaceutical companies to produce sufficient vaccine to permit the entire population to be immunized against H1N1. The federal government would make grants to state health departments to organize and conduct immunization programs. The federal government would provide vaccine to state health departments and private medical practices. Since influenza caused by A/Victoria was active worldwide, industry was asked to incorporate the swine flu into an A/Victoria product to be used for populations at high risk.Before the discussions with the secretary of DHEW had been completed, a member of his staff sent a memo to a health policy advisor in the White House, raising the specter of the 1918 pandemic, which had been specifically underemphasized in the CDC presentation. CDC's presentation highlighted the pandemic potential, comparing it with the 1968–69 Hong Kong and 1957–58 Asian pandemics. President Gerald Ford's staff recommended that the president convene a large group of well-known and respected scientists  and public representatives to hear the government's proposal and make recommendations to the president about it. After the meeting, the president had a press conference, highlighted by the unique simultaneous appearance of Salk and Sabin. President Ford announced that he accepted the recommendations that CDC had originally made to the secretary of DHEW. The National Influenza Immunization Program (NIIP) was initiated.The proposal was presented to 4 committees of the Congress, House and Senate authorization committees and House and Senate appropriation committees. All 4 committees reported out favorable legislation, and an appropriation bill was passed and signed.The estimated budgeted cost of the program was $137 million. When Congress passed the appropriation, newspapers mischaracterized the cost as "$1.9 billion" because the $137 million was included as part of a $1.9 billion supplemental appropriation for the Department of Labor. In the minds of the public, this misconception prevailed.Immediately after the congressional hearing, a meeting of all directors of state health departments and medical societies was held at CDC. The program was presented by CDC, and attendees were asked for comments. A representative from the New Jersey state health department opposed the plan; the Wisconsin state medical society opposed any federal involvement. Otherwise, state and local health departments approved the plan.Within CDC, a unit charged with implementing the program, which reported to the director, was established. This unit, NIIP, had complete authority to draw upon any resources at CDC needed. NIIP was responsible for relations with state and local health departments  and established a proactive system of surveillance for possible adverse effects of the influenza vaccines, the NIIP Surveillance Assessment Center (NIIP-SAC). (This innovative surveillance system would prove to be NIIP's Trojan horse.) In spite of the obstacles discussed below, NIIP administered a program that immunized 45 million in 10 weeks, which resulted in doubling the level of immunization for persons deemed to be at high risk, rapidly identifying adverse effects, and developing and administering an informed consent form for use in a community-based program.The principal obstacle was the lack of vaccines. As test batches were prepared, the largest ever field trials of influenza vaccines ensued. The vaccines appeared efficacious and safe   and that when a person participating in that societal benefit is damaged, society had a responsibility to that person. The proposal was sent back from a staff member in the Surgeon General's office with a handwritten note, "This is not a problem."Soon, however, NIIP received the first of 2 crippling blows to hopes to immunize "every man, woman, and child." The first was later in 1976, when instead of boxes of bottled vaccine, the vaccine manufacturers delivered an ultimatum—that the federal government indemnify them against claims of adverse reactions as a requirement for release of the vaccines. The government quickly capitulated to industry's demand for indemnification. While the manufacturers' ultimatum reflected the trend of increased litigiousness in American society, its unintended, unmistakable subliminal message blared "There's something wrong with this vaccine." This public misperception, warranted or not, ensured that every coincidental health event that occurred in the wake of the swine flu shot would be scrutinized and attributed to the vaccine.On August 2, 1976, deaths apparently due to an influenzalike illness were reported from Pennsylvania in older men who had attended the convention of the American Legion in Philadelphia. A combined team of CDC and state and local health workers immediately investigated. By the next day, epidemiologic evidence indicated that the disease was not influenza (no secondary cases occurred in the households of the patients). By August 4, laboratory evidence conclusively ruled out influenza. However, this series of events was interpreted by the media and others as an attempt by the government to "stimulate" NIIP.Shortly after the national campaign began, 3 elderly persons died after receiving the vaccine in the same clinic. Although investigations found no evidence that the vaccine and deaths were causally related, press frenzy was so intense it drew a televised rebuke from Walter Cronkite for sensationalizing coincidental happenings.What NIIP did not and could not survive, however, was the second blow, finding cases of Guillain-Barré syndrome (GBS) among persons receiving swine flu immunizations. As of 1976, >50 "antecedent events" had been identified in temporal relationship to GBS, events that were considered as possible factors in its cause. The list included viral infections, injections, and "being struck by lightning." Whether or not any of the antecedents had a causal relationship to GBS was, and remains, unclear. When cases of GBS were identified among recipients of the swine flu vaccines, they were, of course, well covered by the press. Because GBS cases are always present in the population, the necessary public health questions concerning the cases among vaccine recipients were "Is the number of cases of GBS among vaccine recipients higher than would be expected? And if so, are the increased cases the result of increased surveillance or a true increase?" Leading epidemiologists debated these points, but the consensus, based on the intensified surveillance for GBS (and other conditions) in recipients of the vaccines, was that the number of cases of GBS appeared to be an excess.Had H1N1 influenza been transmitted at that time, the small apparent risk of GBS from immunization would have been eclipsed by the obvious immediate benefit of vaccine-induced protection against swine flu. However, in December 1976, with >40 million persons immunized and no evidence of H1N1 transmission, federal health officials decided that the possibility of an association of GBS with the vaccine, however small, necessitated stopping immunization, at least until the issue could be explored. A moratorium on the use of the influenza vaccines was announced on December 16; it effectively ended NIIP of 1976. Four days later the New York Times published an op-ed article that began by asserting, "Misunderstandings and misconceptions... have marked Government ... during the last eight years," attributing NIIP and its consequences to "political expediency" and "the self interest of government health bureaucracy" ; New York Times reporter Harold Schmeck's coverage of the ACIP sessions, the president's press conference, and 4 congressional hearings), effective communication from scientifically qualified persons was lacking, and the perception prevailed that the program was motivated by politics rather than science. In retrospect (and to some observers at the time), the president's highly visible convened meeting and subsequent press conference, which included pictures of his being immunized, were mistakes. These instances seemed to underline the suspicion that the program was politically motivated, rather than a public health response to a possible catastrophe.Annex 11 of the draft DHEW pandemic preparedness plan states, "For policy decisions and in communication, making clear what is not known is as important as stating what is known. When assumptions are made, the basis for the assumptions and the uncertainties surrounding them should be communicated" (Neither CDC nor the health agencies of the federal government had been in the habit of holding regular press conferences. CDC considered that its appropriate main line of communication was to states and local health departments, believing that they were best placed to communicate with the public. MMWR served both a professional and public audience and accounted for much of CDC's press coverage. In 1976, no all-news stations existed, only the nightly news. The decision to stop the NIIP on December 16, 1976, was announced by a press release from the office of the assistant secretary for health. The decision to reinstitute the immunization of those at high risk was announced by a press release from the office of the secretary, DHEW. In retrospect, periodic press briefings would have served better than responding to press queries. The public must understand that decisions are based on public health, not politics. To this end, health communication should be by health personnel through a regular schedule of media briefings.This decision is worthy of serious question and debate. As Walter Dowdle (The Delphi exercise of Schoenbaum in early fall of 1976 (As Dowdle further states (When lives are at stake, it is better to err on the side of overreaction than underreaction. Because of the unpredictability of influenza, responsible public health leaders must be willing to take risks on behalf of the public. This requires personal courage and a reasonable level of understanding by the politicians to whom these public health leaders are accountable. All policy decisions entail risks and benefits: risks or benefits to the decision maker; risks or benefits to those affected by the decision. In 1976, the federal government wisely opted to put protection of the public first.


There are numerous benefits to the research community from data sharing, and yet the open sharing of participant level data is not without potential pitfalls. In addition to the scientific community, the interests of study participants who volunteered their data must be considered, along with the interests of study investigators who expend a substantial amount of effort into the design, conduct, and analytical plans for the study. The National Heart, Lung, and Blood Institute (NHLBI) has developed a data-sharing protocol focused on balancing the interests of study participants, study investigators, and the research community with independent oversight by the NHLBI IRB. The data repository presently includes individual level data on more than 560,000 participants from 100 Institute-supported clinical trials and observational studies. There are many potential uses of existing data: meta-analyses, applications of innovative statistical methods, replication, novel new analyses, cross-study comparisons, and sample size estimation for new studies. The benefits to the research community of data sharing are consistently heralded in the literature -6, and yThe NHLBI data repository presently includes individual level data on more than 560,000 participants from 100 Institute-supported clinical trials and observational studies. Sharing this clinical data in a manner that balances the interests of study participants, study investigators, and the research community is the subject of this commentary.A formal data sharing policy, applicable to Institute-supported contract studies, was first established by the Institute in 1989 under then Director Claude L’Enfant. This first data-sharing policy timed release of data to within 3 years of ‘major publications’ and described generally the data that were to be removed from a study dataset prior to release. Although a formal data-sharing policy for contract-supported studies had been established, the availability of these datasets was not well-known, there was a lack of guidance on what process should be used to distribute datasets, and it was unclear as to what data should be made available. A revised policy, incorporating specific data release timelines, guidelines for data submission, and the data request process was developed in 1999. Since all of the data for the data repository were derived from human subjects in both ongoing and closed studies, the policy was submitted to the NHLBI Institutional Review Board (IRB) as a formal protocol and was first approved by the NHLBI IRB in 2000. The NHLBI IRB continues today in its oversight role to annually review the activities of the data repository.The data-sharing protocol has evolved over time, expanding to include grant-supported studies as well as contract-supported studies. Clarification of the common rule regarding local IRB review for secondary analysis of existing data provided additional guidance on how requests for data should be reviewed, and studies depositing data into the repository are now required to certify that the data can be shared with outside investigators.The data repository protocol can be divided into three aspects: rules for when data will be released and what data to include, rules for submitting data to the repository, and rules governing how data will be shared.The data released to the general research community through the data repository consist of all data collected during the conduct of the study including: baseline, interim visit(s), laboratory measurements, and outcome data. To minimize re-identification risks and provide reasonable protection for participant privacy, the de-identification procedures for data included in the repository generally follow the HIPAA privacy act , these iDatasets are released following a standard timeline. Study investigators are given a protected period of time (2 years) to prepare key manuscripts from the study. In this manner the data are made available to the general research community within a reasonable time frame and provides the investigators who collected the data time to publish study results.Data collection for clinical trials is generally predefined with specific starting and ending dates; however, observational studies may collect data over many years. Therefore, the protocol defines data release in a slightly different manner depending on the study type. Specifically, the protocol states that data from observational studies are made available: (1) 3 years after the last participant visit for a clinic exam cycle or close out date for event ascertainment; or (2) 2 years after the exam or surveillance data are made available for within study use. Ongoing observational studies will therefore tend to have periodic updates to their data. Data from clinical trials are made available 2 years after publication of the primary outcome paper or 3 years after the end of clinical activity.It is important to note that most large clinical trials and observational studies have active publications/presentation committees that are open to collaborations with outside investigators. These studies are essentially open to immediate data-sharing using study-specific internal policies.Release of data through the data repository is required for Institute-supported contract studies and may also be required for certain large grants or cooperative agreements. The inclusion of grant-supported studies was introduced in 2005 and applies to studies reviewed and initiated after October 1, 2005. In brief, grant-supported studies with direct costs equal to or greater than $500K in any 1 year and identified as being of high programmatic interest, along with cooperative agreements with 500 or more participants are required to submit data to the data repository as part of the grant award.All data submitted to the data repository must be consistent with the informed consent. Participants explicitly requesting that their data not be shared must be removed from all repository datasets and any other consent restrictions must be noted. For example, the informed consent for the Hemochromatosis and Iron Overload Screening Study (HEIRS) indicated that participants’ data would only be used for ‘iron-related and hereditary hemochromatosis studies’. Therefore, any requests for HEIRS study data must have an iron-related focus.Following on the database of Genotypes and Phenotypes (dbGaP) experience, institutions submitting data to the data repository are required to certify that the data can be shared. In brief, the certification affirms to the NHLBI that the informed consent explicitly permits sharing data with other investigators, or the depositing Institution’s IRB has approved the sharing of the participants’ data.http://www.biolincc.nhlbi.nih.gov. The website is maintained by the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) program. The online application for study datasets include: (1) a description of the research project; (2) local IRB review or institutional certification of exemption from IRB review; and (3) agreeing to the terms and conditions of a data use agreement  since both biospecimens and data can be obtained from the NHLBI repositories). Terms of the RMDA include provisions limiting use of the data to 3 years, prohibits transfer of the data to another party, requires appropriate computer security measures, and specifies the acknowledgment to be used in manuscripts. Both the investigator and the Institution are required to sign and agree to the terms of the RMDA. Applicants are not subject to a scientific review, but instead an administrative review is conducted to ensure the project is within the spirit and intent of the data agreement. Likewise, there is no requirement for screening manuscripts prior to submission to a journal. The absence of a scientific review or pre-submission review of manuscripts avoids any perception of blocking access or controlling research; however, this does allow for the possibility of misleading or incorrect analyses to be published. The possibility of intentionally misleading analyses is mitigated to some degree through the open nature of the repository in that replication is possible with the identical dataset. Avoiding unintentionally incorrect analyses is far more difficult and is largely only correctable post publication.Applications for study datasets in the Data Repository are done online at A summary of the clinical data and biospecimen resources available are provided in Additional file A collaborative approach, utilizing the experience and expertise of study investigators, is the most productive method of data-sharing for ensuring high quality manuscripts. The NHLBI data repository fulfills the niche of providing opportunities for secondary analysis of existing data when collaborations are either unfeasible, or not desired. Participant data are released, after study investigators have had a 2-year protected period of time, in a manner consistent with the informed consent, and is generally redacted to meet or exceed HIPAA requirements to maintain participant privacy.The NHLBI has made a commitment to the sharing of research resources to the widest possible audience to maximize the value of Institute-supported studies. Through a website portal, the Institute financially supports the infrastructure to efficiently process, communicate information, and distribute to the research community data from more 560,000 study participants and 4.6 million biological samples.Bolded studies have samples in the biorepository and the footnotes indicate stored biospecimen types.Observational studies, clinical trials, and transfusion medicine studies with data and/or samples in the NHLBI data and biospecimen repositories. Study acronym and number of participants are in parentheses. Click here for file


Prevailing sociopolitical and economic obstacles have been implicated in the inadequate utilization and delivery of the Armenian health care system.A random survey of 1,000 local residents, from all administrative regions of Armenia, concerned with health care services cost and satisfaction was conducted. Participation in the survey was voluntary and the information was collected using anonymous telephone interviews.The utilization of health care services was low, particularly in rural areas. This under-utilization of services correlated with low income of the population surveyed. The state funded health care services are inadequate to ensure availability of free-of-charge services even to economically disadvantaged groups. Continued reliance on direct out-of pocket and illicit payments, for medical services, are serious issues which plague healthcare, pharmaceutical and medical technology sectors of Armenia.Restructuring of the health care system to implement a cost-effective approach to the prevention and treatment of diseases, especially disproportionately affect the poor, should be undertaken. Public payments, increasing the amount of subsidies for poor and lower income groups through a compulsory health insurance system should be evaluated and included as appropriate in this health system redesign. Current medical services reimbursement practices undermine the principle of equity in financing and access. Measures designed to improve healthcare access and affordability for poor and disadvantaged households should be enacted. The socio-economic decline following the collapse of the Soviet Union had a very drastic impact on the Armenian healthcare system. The vain attempts of healthcare reform have been hindered by a number of economic challenges. These severe social-economic conditions and the failed efforts to implement a state medical insurance program have caused a decrease in subsidized health services and utilization . Low purPreviously it was believed that the free market could serve as a rational resource allocation mechanism for the healthcare system in Armenia. Since the mid-1990s the government has started to work on a radical program of reforms but many of these efforts, in particularly those from the South Caucasus region , have had no effect . BetweenPublic financing of the Armenian health system has increased in relative terms in recent years and from 2000 to 2011 it increased from a total of approximately $17.8 million to about $173.6 million (or 62.5 billion AMD) i.e. approximately tenfold, nevertheless it is still low [The physical conditions in health posts and polyclinics are often poor and staff has had little incentive to treat patients with respect. On the one hand the reform provides the patients with the right of choosing their primary physicians, as well as reduces inappropriate and overly expensive secondary medical care; however, on the other hand, the health care reform limits the patient’s rights of access to direct specialist care. If the primary physician does not agree to refer the patient to a specialist, there is no way for the patient to refer himself to the secondary setting without directly paying into it and without a letter of referral from a primary physician in all except for emergency cases. Thus, even though the public costs are greatly reduced by the reform, actual out-of-pocket costs increase since the patients who chose to bypass the primary care physician referral process, and see a specialist, will have to pay for the treatment.The role of private health facilities is becoming more and more apparent in the whole healthcare framework of Armenia. According to a World Bank report (2010), the private health care spending was more than 1.2 times higher than public expenditures in 2009 . PrivateAlong with the decrease of government’s ability to socially protect the population, the active development of a shadow market of paid medical services has been observed. The growing informal sector of the economy caused a near collapse of the old social insurance and safety nets mechanisms. Estimates of the black market health care economy in Armenia cannot be accurately estimated. According to World Bank in 2000, the share of patients making ‘informal’ reimbursements was the highest among CIS countries, reaching 91%, as compared, for example, to 74% in Russia . Access The government has been trying to implement Health Insurance System for 10 years. However, in Armenia, the market literally fails to provide health insurance. At the same time a significant part of the population couldn’t afford to buy private health insurance, and current tax laws do not give incentives to the employer to provide health insurance to its employees. Besides, the social security taxes that employers currently pay for their employees’ wages and income taxes that employees pay, an additional 9% or even 3% tax on wages is not politically feasible. At this stage, given the government’s relatively low revenues, public health insurance seems to be cost prohibitive. If people are struggling for survival every day, they are less willing to pay insurance premiums in advance in order to use services at a later point in time. The low income of the population and the existence of a shadow economy make the development of public and even private health insurance very difficult.In order to reduce the shadow turnover in health sphere in Armenia a co-payment mechanism was introduced into health care services in March 2011. It has been implemented with differentiated approach in the regions compared to Yerevan, which means that the cost for healthcare services is significantly lower in the regions. While one part of the amount was directed to increasing salaries of medical workers from about $150-$200 (60.000-80.000 AMD) to about $500-$650 (200.000-250.000 AMD) depending on the hospital and number of patients, the other part of the money accumulated in the form of co-payments was intended for the improvement of the quality of healthcare services, provision of hospitals with medicine, equipment and tax payments [The State Health Agency (SHA) in Armenia that was established in 1998 is responsible for purchasing services from providers through contractual mechanisms. Since then the public budget for health care is disbursed to health care providers through contracts between the SHA and the providers. Those funds are directly transferred from the Ministry of Finance (MoF). The main tasks of the SHA are: contracting health care providers for services in accordance with Basic Benefits Package (BBP), ensuring the target use of state financial resources and reimbursement of the health care providers and quality assurance. The contractual arrangements between the SHA and the providers, however, are defined relative to the health services that are provided using state property such as infrastructure and equipment. This represents an unclear arrangement since according to the existing regulation the SHA has limited ability to supervise the functioning of the contracted enterprises, and can only solve the “problems of the filed within the limits of its jurisdiction without violation of the independence of subordinate enterprises”.Although the range of benefits nominally available to the poorest under the program of State Guarantees is greater, the SHA payments do not act as a full “catastrophic insurance” program. In general, the amounts paid to hospitals through the SHA are less than their costs, and these institutions continue to collect sizeable out-of-pocket payments from patients. In primary care, chronic disease drugs are nominally a guaranteed benefit, but primary care budgets are inadequate to cover these costs and patients continue to pay large sums out of pocket. Except for the poorest, there is no government payment for hospital care for many chronic and degenerative diseases. For this category the levels of SHA payment are below cost , so those who must be admitted to hospital pay substantial amounts. Hence, state funding is not even sufficient to assure guaranteed free services for socially vulnerable groups . In thesDespite the stability of some health indicators in Armenia in recent years many of these are still worse today than they were in 1990. The accessibility of healthcare in Armenia has clearly worsened during the researched period of time. Armenians continue to experience poor access to health care despite the sufficient number of health facilities and medical workforce. The number of patients admitted to the hospitals of the Ministry of Health in 2010 was just over a third of the number admitted in 1990, while all hospital admissions decreased by almost 50%, meaning the cost effectiveness of the hospital system has also declined [Between 1998 and 2010 the morbidity rate has increased. At the same time, the morbidity of population and children 0–14 years diagnosed the first time has increased. The overall birth rate from 1970 to 1990 was around 22 per 1000 population, but has since dropped to 13.8 in 2010. Between 1990 and 2000, the birth rate sharply decreased while the overall death rate comparatively increased. This can be explained by the fact that since the beginning of the transition towards a market-oriented economy, Armenia has faced a number of difficult challenges; including a major tragic earthquake of 1988, the Nagorno - Karabakh War, referred to as the armed conflict that took place from February 1988 to May 1994, a blockade enforced by Turkey and Azerbaijan since 1993 (in place now for over 19 years), an energy crisis, recession and economic collapse. This combination of events has had severe consequences. Economic decline has placed Armenian health institutions in jeopardy, hindering reforms. Gains in freedom have been accompanied by a loss of many basic economic and social services that the population had come to enjoy and expect. Thus, the population growth rate decreased along with natality rate . Life expectancy at birth has remained high - estimated at 71 years for men and 78 years for women during 2010. Both indicators were higher than those of 1990. It is difficult to adequately explain the data, because from 1990 to 2011 the value of this indicator increased. During the Soviet era, Armenia had one of the best developed health care systems in the Soviet Union (SU) [The household survey implemented by the USAID Primary Health Care Reform (PHCR) in 2006, revealed that 39.5% of sick people did not seek medical treatment because of financial constraints. In fact, 42.8% of sick people who were eligible for state guaranteed free-of-charge health care services didn’t, because state funding was far less than the real cost of treatments. Moreover, many patients who were eligible for free outpatient drugs were forced to purchase medications in the market versus state funded pharmacies due to lack of supply. Lastly, self-care was found to be 36.2% and of these people, 95.3% did not visit a doctor due to financial constraints. The study provided some answers behind the population’s morbidity, defined as not seeking medical care and lack of access, reveals the following important feature of population’s health care related behavior. The indicator for not meeting with a doctor while needing medical care is significantly lower for children. The remote distance and time was a hindering factor to visit a doctor for only 1.2% of respondents and 3.5%, respectively. Nonetheless, even with a free of charge PHC service enacted in 2006 the survey revealed that 26% of respondents did not visit a PHC facility .Implementation of the household health expenditure survey by the USAID Primary Health Care Reform (PHCR) in March 2009 provides an opportunity to assess the progress made by Armenia in addressing the equity of access and affordability of healthcare since the previous such survey in 2006. The survey revealed that health expenditures were not evenly distributed. Over 30% of the richest quintile reported receiving outpatient services in 2008, but this fell to 20% - 25% of households in the next two income quintiles and only to 17% for the poorest households.The main reason for not using health care was the lack of financial means - 78% in 2009 with comparison to 47% in 2007, self-treatment 43% (11% in 2007) and other  10% (11% in 2007) . The houAccording to another, 2007 Integral Living Conditions Survey (ILCS), only about one third of respondents who reported being sick consulted a doctor. Among people consulting a doctor the share of those living in Yerevan was higher (38.9%) than those living in rural areas (28.9%) .The 2009 ILCS data revealed, that the share of people who consulted a doctor varied also by poverty status. While 35.3 percent of the non-poor consulted a doctor for advice or treatment when sick, only 21.4 percent of the poor and 1.2 percent of the extremely poor did so. The majority of population (47.1%) consulted public medical facilities when sick and only insignificant part (5.4%) go to private clinics. At the same time, a significant share of the population (47.5%) consulted the drugstore staff.Policlinics are among the most commonly visited public health care facilities (58%), since 2006 the entire population  has been entitled to free ambulatory-polyclinic services, including physician fees, some of the most simple and rather not expensive primary lab and diagnostic tests, such as the cardiogram, X-ray, fluorography, the biochemical analysis and so on. Polyclinics were visited by 63% of Yerevan residents, compared to only 43% in the rural communities. From the view of the poverty status, policlinics are mainly visited by the very poor (75%) and poor (61%), while as hospitals and private facilities, including the expensive diagnostic centers are used mainly by the non-poor. The extremely poor never visited private medical facilities, even the healers. Diagnostic centers were visited by 97 percent of the non-poor and 3 percent of the poor.In the bottom quintile of the population, only about one quarter of those reporting sickness received professional care, while over half of the sick in the wealthiest quintile received professional attention. The type and most probable quality of health care received also varied with income. The utilization of healthcare services in the poorest quintile was 25 times lower than the average utilization rate of these services , whereas for the richest quintile this indicator was 4.2 times higher than the average [Our study differs from the above-mentioned surveys by its aim, objectives and methods. The aim of our study was more specific and focused only on the health sector , while other surveys with more informative character were intended to inform the public about the living conditions and social situation in the country, described poverty trends nationally and by different socioeconomic, demographic and geographical classifications, or showed consumer expenditures on all types of services, including health. The purpose of this project was to explore the respondents’ awareness about free-of-charge medical services, the level of their satisfaction with provided medical care, the main reasons for the high level of unmet needs for health care, health inequalities and inequities. During our survey the information was collected using anonymous telephone interviews, while during other surveys face-to-face interviews with the household head or another knowledgeable adult member was used. We tried to contribute to the development of public health policy in Armenia by exploring the implications for delivering health services aimed at reducing health inequalities and inequities through action on the socio-economic determinants of health.We reviewed and analyzed the results of several household and patient surveys, specifically as they related to the utilization and accessibility of healthcare services, the reasons for not visiting a doctor, patient satisfaction with supplied services, and payments for healthcare. We conducted a literature review and analyzed national health data to understand if there was a correlation between the inequality in healthcare utilization/accessibility and health status in Armenia, and to identify the factors of their impact on the health of the population.The survey of population health was conducted within the framework of the Armenian National Science & Education Fund (ANSEF) program in 2010 according to a specially developed questionnaire. The research was approved by the Institutional Review Board of Yerevan State Medical University (YSMU) after M. Heratsi . Particular attention was given to the assessment of medical care satisfaction and to the assessment of the level of household expenditure on medical care. Stratified random sampling was used for the selection of respondents (1000 residents), with which there was an equal chance that each female or male respondent could be selected for inclusion in each stratum of our sample. The preliminary random selection was made among administrative divisions of Armenia on the basis of proportionate-to-population-size approach. We divided the respondents into groups or strata by urban/rural areas and the data was weighted by age and gender to bring the realized sample in line with target population parameters. Then, within each stratum, we randomly selected survey respondents.A random sample of local residents was surveyed regarding the current usage of medical services, assessment of medical care satisfaction, household health expenditures and payments for healthcare, patient satisfaction with supplied services and perception of the healthcare system. Participants were also asked questions concerning:demographic characteristics: sex, age (mainly 18-60+ years old), etc.;education and occupation of respondents;types of entities where the respondents work: public, private, NGO;self-estimation of the basic aspects of health condition by the respondents;estimation of local health care system activities by respondents;risk factors and conditions influencing the health of population; social-economic, social-psychological, social-demographic, ecological, geographical, medical-organizational, etc.Participation in the survey was voluntary. The data were collected using anonymous telephone interviews taking into account the fact that more than 90% of households have access to public telephone networks and 86% of Armenia's population uses mobile phones ,27. TherCalls were made to various regions based on the population size. Individual participants’ identifiers were not recorded. Quality control was managed through monitoring the interview process. Investigators were not purview to individual interviewee’s responses.The ratio of respondents by gender was the following: female – 53,2%, male – 46,8%. The percentage ratio of age groups was as follows: 28% were between 18–25 years old; 32% - 26–45 years old; 24% - 46–60 years old; and 16% were over 60 years old. The main portion of respondents (79%) had higher education. According to their social - professional status respondents were - service employees −24%, specialists - 22%, students - 19%, retired - 10%, managers - 8%, entrepreneurs - 5%, housewives −9%, and the rest were unemployed −3%. The majority of respondents worked in the state structures (40%): budgetary or public organizations, 29% - in the private sector and rest of them in NGOs and other entities.The analysis of the survey revealed that among the risk factors affecting the health of the population were noted: social-economic - 37.3%, social - psychological - 21.3%; social-demographic - 5.3%; ecological - 16%; geographical - 9.4% medical-organizational - 10.7%. According to the respondents the utilization of health care services was low, particularly in rural settlements. Low utilization of health care services in rural areas and to some extent also in small and medium sized cities is explained due to the lack of physical access to health care, remoteness from the nearest health facilities, dilapidated unheated buildings during extremely cold winters, often due to complete absence of pharmacies or their poor drug assortment: only few drugstores are enlisted for provision of free of charge drugs for vulnerable groups, which are either physically inaccessible, or many do not know their exact list and addresses. Some of the reasons also include lack of most basic supplies of equipment, a substantial cutback in hospital beds through mergers and closures due to the government optimization plan (whereas cities still have excess capacity). Besides, many respondents from these settlements reported that they prefer self - treatment or a visit to the healer.According to our survey, 60% of respondents participating in the survey were sick, out of these 24% frequently were sick, 20% patients had chronic pathology and 16% were disabled. Affordability was the main concern for not using medical services, especially inpatient. 44% of the respondents could not afford and consequently did not have access to services; on a paid basis it was accessible to only 52% and only for 4% from all of the respondents eligible for BBP, it was accessible free of charge.Results indicate utilization of health care is low even for Armenians who qualify for the government health care program BBP. This is in part because the government sets payment at rates that may not cover providers’ expenditures. As a result, BBP participants are pressured to give additional informal payments in exchange for health services as it is not based on real costs of services and thus contributes to unofficial or illicit payments. Moreover, all health services and drugs that are not included in BBP must be paid directly by the patient. For instance, in 2009 some 18 percent of population was entitled to the basic benefit package However, only 49% of the eligible population used health services under BBP, including 77% of the extremely poor, 51% of the poor, and 6% of the non-poor. Recipients of family benefit, who have used BBP in average spent monthly $31.4 (11401 AMD) per person, including $0.6 (214 AMD) under the BBP, informal payments amounted to $1.6 (587 AMD), $15.5 (5649 AMD) on medicaments, and the remaining amount channeled to official payments both at public and private medical facilities. As for the total number of population having used healthcare services (both paid and free of charge), the actual monthly amount per one patient totaled $56.8 (20625 AMD), including $2.5 (904 AMD) as informal payments, and $22.3 (8104 AMD) on medicaments, with the remaining amount spent as official payments for treatment [The low affordability for using medical services can be also explained by the simple fact that only 8% of respondents received an income over $260 (over 100 000 AMD) per capita per month, while the overwhelming amount of respondents lived on an income of $80 (30 000 AMD) or less per capita per month, which is less than the minimum wage.Population awareness about free-of-charge medical services reached only 40%. The frequency that people utilized medical aid is shown in Figure Many of them prefer the ostrich method: Better not know about our disease, than know about it and not be able to treat it because of lack of access to paid or more expensive services and drugs. The majority of the population visited public medical institutions when being sick and only 4% went to private clinics and hospitals . Family practitioners and specialists of polyclinics were the major healthcare providers, as since 2006 the entire population  has been entitled to free ambulatory-polyclinic services, but these are only some of the most simple and inexpensive services, the rest of health services that are not included in the list must be paid directly by the patient . Results are not too surprising, considering the amount of the average monthly per capita monetary income. At the same time, the World Bank (WB) shows that the monthly size of “consumer's basket” in Armenia has made $112.8 (42158.7 AMD) and a “consumer's food basket” - $63.7 (23818.5 AMD) in the fourth quarter of 2010 . It turnAbout 40% of respondents mentioned lack of trust in PHC providers and their qualifications. Trust has a strong emotional role in the success of the treatment efficiency. Treatment begins with the establishment of close personal contact between patient and doctor. In many cases, patients refuse to receive treatment due to mistrust in doctors. The main causes of distrust in the health care providers were because of technical incompetence and impersonal care, difficulty communicating with physicians, absence of incentive to treat patients with respect, provider’s focus on profit. These reasons were similar for men and women.Technical incompetence was also indicated as a key aspect of distrust. It was explained by distrust of the respondents towards the doctors, who in their opinion, made a wrong diagnosis, gave the inappropriate treatment and provided the improper follow-up care.Impersonal care was explained by many respondents as absence of care, empathy, patience and honesty. They shared about their experiences where the doctors barely talked to them and did not examine them, instead they immediately wrote a prescription, not even looking at them, if they didn't feel that they could get paid. Respondents also talked about how experimentation and beliefs about experimentation in the health care setting affected their views of the trustworthiness of doctors.Some respondents expressed the view that doctors are there to make money, and many of them charge for various forms of unnecessary laboratory tests, procedures, medicines, services, etc. Payments are mostly out-of-pocket, contributing to the prosperity of the informal sector and undermining the principle of equity with respect to both financing and access. As to out-of-pocket costs for healthcare increase, requiring higher spending by households, the poor become much less likely to seek out professional care. Due to this cycle, the respondents group with the lowest level of income typically has the lowest health potential. This group also tends to have the most problems obtaining qualified medical assistance and medical goods, as use mostly the free of charge outpatient health services.Only 57% of the sick (including many disabled and elderly with chronic diseases) in the poorest quintile refer to a doctor. This percentage could be much less if the ambulatory-polyclinic services since 2006 for most simple and inexpensive services have not been free. In contrast, 96% in the richest quintile used private clinics, inpatient and preventive services, which are not free. Moreover, their per capita expenses at diagnostic centers exceed total expenses made at other health institution.The share of healthcare expenditures in total consumption for the richest quintile group was much higher compared to the poorest quintile group (9.1%and 0.1% respectively). The utilization of healthcare services in the poorest quintile is 17.1 times lower than the average utilization rate of these services (in AMD), whereas for the richest quintile this indicator is 5.8 times higher than the average. Hence, healthcare is increasingly considered a privilege for the elite, less and less available for the poorer part of the population.Thus, during the 1990s in Armenia both socio-economic situation and the policy responses led to an exacerbation of the crisis in the health care system with severe negative consequences for the population, especially in terms of equity and financial risk protection, unlike some other countries, for example, Kyrgyzstan and the Republic of Moldova, that had a clear set of policy objectives and a coherent approach to selecting policy instruments, and where the economic crisis was turned into a health reform opportunity .A very important methodological conclusion can be derived from the trends for several national health indicators observed from 1990 to 2011. Utilization/accessibility to health care and the role of the state as a healthcare provider are open questions in Armenia.The analysis of the surveys revealed that adverse outcomes of healthcare were observed in Armenia. On the one hand, the expenditures on medical services are high and continue to grow quickly, and on the other hand, access to the treatment is limited, and preservation of health becomes too expensive for a significant part of the population. The demand of health services and the level of utilization remain dramatically low, particularly in rural areas and among the poor. The way healthcare services supply is organized in Armenia shows social inequality in the access and utilization to such care. The qualitative and quantitative usage of medical services by the population is highly polarized which in its turn aggravates sharp social stratification and has an increasingly destabilizing social effect. As a result, the high level of poverty, and inequality of income distribution have had a negative impact on the health of the population and has also led to an increasing gap in the quality of medical care between the poor and the wealthy. The reliance on direct out-of pocket and informal payments, development of a grey market of paid medical services, are serious problems which have accumulated in the healthcare, pharmaceutical and medical technology sector, undermining the principle of equity with respect to both financing and access. In its turn, informal payments tend to penalize poor households and can have a significant impact on further access to health care services ,35. The The survey findings reiterate that lack of trust towards doctors’ skills will also remain as another major challenge for policy makers when reforming PHC provision. We believe that with the development of the general practice system, the patients’ choice of physicians will become increasingly meaningful. The right to choose a doctor should also enhance patients’ trust and quality of care, as physicians’ pay now depends on the number of patients, therefore, we can expect that they will invest more effort in ensuring patient satisfaction. In our view, the reform of primary health care, aimed at strengthening the link between patient numbers and physician pay, may encourage the movement of resources in this sector, improve the poor physical conditions in health posts and polyclinics, create more incentives for the staff to treat patients with respect and also promote the general practice model, all of which will enhance the standards of the sector and lead to greater patient satisfaction. An adequate strategy for training and re-training human resources for primary care needs to be developed in order to improve the trust of the general public in the quality of primary care providers. It is necessary to regain people's trust in doctors, to bring people back to the policlinics. Regaining trust is important for the sake of improving the results of patient satisfaction.Despite the fact that practically almost all doctors and health institutions are de facto heavily involved in commercial delivery of health services, the private health sector in Armenia is still in need of further development. The establishment of private hospitals and clinics are still limited, because the private sector does not see for-profit health institutions as economically viable and the decline in demand for health services, make this market unattractive for private investment .Given the radical decline in the availability of public revenues that had occurred by the mid-1990s in Armenia the initial focus of reforms was on trying to specify the BBP more precisely. This seemed rational; however the ability to enforce a package of entitlements depends critically on the system's ability to purchase them. This means that there must be a purchaser in place, supported by information systems that enable a link to be made between provider payment and clinical/patient data from providers. The existence of such systems makes it possible not only to declare the entitlements of the population, but actually to purchase them. Without them, the evidence suggests that the effort at formal rationing will be undermined by informal methods .The reform experience also suggests some lessons with regard to what not to do, either in terms of policy or implementation. Many health systems face pressures to calculate the “true” or “real” cost of their benefits packages. This has been the case in Armenia (as stated above) and in several other countries (such as Ukraine and Georgia) . Worse, Starting the financing reform process with major modifications of the BBP is also politically dangerous, as the specification of entitlements and obligations is perhaps the most visible part of health financing policy to the population. If government is unable to deliver this (Armenia's experience is instructive here), the credibility of the entire reform process will be threatened. Social insurance may not be a panacea, particularly in a low-income setting. Armenia’s experience indicates the difficulty of reaching high levels of coverage using social insurance alone. There is a large level of informality and, in order to cover vulnerable groups, the reforms had to be adjusted to incorporate special targeting programs to reach those not covered by social insurance. The programs should be introduced at all points and levels for all strata and groups of population. In which it should be based on the principle of universal and equal access to health care. Otherwise, these healthcare programs will face a serious threat of scattering out and not serving their objective. Only strategically designed out-of-pocket payments - in conjunction with social insurance - can play an important role in ensuring sustainability of health care financing. They help moderate demand and ensure that poor and other vulnerable groups receive coverage for essential health care and protection from catastrophic expenditures.We should strive for a system that covers everyone, to make the health system more responsive to the needs of the poor. Considering the issues of accessibility and utilization of health care services, as well as high prevalence of unofficial out-of-pocket payments, the growth of public spending in the medium to long term shall be among the top priorities of the national policy in the sector. However, apart from increasing public funds for health care, mainly hospital care and chronic disease medications, Armenia should explore alternative delivery methods for reaching out to the poor. In our view, in particular the support of private funding, which comes mainly from two sources - copayments, that vary with the services consumed and monthly contributions are also essential for a sustainable health system. The introduction of a co-payment mechanism for Armenia's predominantly public healthcare system in 2011 will increase the transparency of patient expenditure and as a consequence, to some extend, will reduce corruption and the widespread use of unofficial payments to medical employees, as well as successfully expand health care coverage. In its turn, the combination of a transparent payment system and additional funds generated by the co-payment mechanism will benefit healthcare finances and support growth for healthcare service providers, including drug makers.Armenian government should make more deliberate efforts to improve the domestic pharmaceutical industry, reduce the nation's reliance on imported drugs and shift spending away from expensive imported medicines towards generic drugs, as the substitution of imported pharmaceuticals with domestically-produced medicines is an effective and reliable way for healthcare services cost reduction.In conditions of widespread absence of pharmacies, especially in rural areas, we are of the opinion that, from the viewpoint of both awareness building and ensuring full access to drugs, it would be appropriate to delegate the responsibility for provisioning the mentioned drugs only to drugstores located in polyclinics and/or family doctors with the corresponding formalized agreement with polyclinics. They should be put in charge of distributing not only drugs provided free of charge and with privileged conditions, but also a certain quantity of drugs needed for emergency medical care. This measure can improve the state control over these resources and provide more efficient use of public funds, promoting access to drugs, particularly for vulnerable. This could be accomplished through public payments (monetary vehicles) that increase the amount of subsidies per individual to poor and lower income groups by implementing a compulsory health insurance system. In addition, the MoF to independent auditors should protect the budgetary allocations for basic health services by emphasizing the positive relationship between investments in health and poverty reduction.It is essential in order to stop the downward spiral of healthcare utilization by reducing cost of services, eliminate informal payments to shadow operations in health care services and medical care sectors. In addition, keep financially strapped hospitals in low-income areas functioning with the help of special state funds and expand opportunities for the poor to obtain improved access and treatment.Each country used a different set of policy instruments, but they exhibited important similarities in the process. However, for the effective reform process all of the key elements  need to be defined, integrated, coordinated and managed in an objective way, incorporating evidence-based policy approaches.There is no endpoint to the reform process, and good stewardship is essential in order to identify when changes are needed and to develop the appropriate responses. Regulatory and administrative capacity is critical to the success of reform, including successful expansion of health care coverage and must be backed up by a commitment to provide access to quality health care services. For instance, the development of public hospitals’ management capacity and the promotion of participatory management will lead to improvements in hospital performance.International experience also has shown that а critical reform implementation step is the establishment of a new agency responsible for pooling funds and purchasing services, which typically goes hand-in-hand with the introduction of a new dedicated tax . Experience shows that many successful reformers began with the simultaneous introduction of a new dedicated  tax and a new agency responsible for pooling and purchasing. Simply creating the new agency, as it was in Armenia, is not enough to make it an effective agent of change. A new agency needs to be accompanied by measures to create or strengthen the purchasing function. In most countries, it was necessary even to start with a new institution outside of the MoH, with an off-budget status to overcome the rigidities of the inherited system.Most transition of the countries introduced payroll or otherwise dedicated tax-funded compulsory health insurance funds in an effort to reverse the revenue decline experienced in the early transition period. The impact of this change on both the level of public revenues for health – and on wider policy objectives such as promoting universal financial protection and access to care – depended critically on the extent to which this reform was coordinated with corresponding changes in the level and flow of general budget funding, and on the coordination of these different sources of public funds via changes in pooling arrangements. However, the impact of introducing a dedicated tax for health on the level of funds is hard to discern due to concomitant underlying changes in fiscal context in these countries. For the CE countries that had a less severe economic transition, changes in the level of public revenues raised via dedicated taxes grew in line with changes in the overall economy, similar to overall public revenues. For the more severely affected countries that also introduced payroll tax, the level of funds raised was not great. In each case, however, corresponding reforms with regard to the allocation of general budget revenues to health were of critical importance.The examples are the positive experiences of the Czech Republic and the Republic of Moldova, which introduced defined central budget transfers to their insurance funds on behalf of specific non-contributing groups of the population. The evidence from the region suggests that it is essential that clear commitments for budgetary funds are designed as an integral part of the compulsory health insurance introduction, in order to avoid offsetting revenue declines , and further suggests that such commitments are more likely to be implemented when the source of budget funds is the central rather than decentralized levels of government.An efficient tax collection mechanism and a low rate of tax evasion have also helped ensure that the necessary resources will be available to finance public spending. The current tax laws in Armenia should be improved, to give more incentives to the employer to provide health insurance to its employees. Besides, the tax should not be high, especially in low- income countries , but it seems to be necessary as a means to create new institutional arrangements that generate opportunities to drive broader health financing reforms.Many of the countries that introduced compulsory health insurance also changed the nature of entitlement from citizenship to contribution. In doing so, they faced the problem of creating explicitly uncovered population groups for the first time . Related to this was the possibility of introducing a new form of fragmentation: different systems for the insured and uninsured parts of the population. Creating such parallel systems could have contributed to overall efficiency and equity problems, as has frequently been the case in many low and middle-income countries that introduced compulsory health insurance in contexts in which a large share of the population is not employed in the formal sector -40. FromThere is a need to create a strategy to reduce fragmentation and align incentives. Critical to this is the strengthening of purchasing mechanisms in the system and altering the flow of general budget funds from subsidizing supply to subsidizing the purchase of services on behalf of the population. Related to this, in their turn, are reforms in pooling to enable reduced fragmentation or at least explicit coordination of the use of funds from different public sources.The development of information systems is essential, as investments in computer systems have allowed financial managers to monitor flow of revenues daily, have facilitated the implementation of new payment mechanisms to enhance provider efficiency and performance. Despite some investments in information technology, Armenia currently faces extensive demands in this area. For Armenia, it would be wise to learn from the reform experience of other countries, and to accelerate its reform since experience in health care reform in some of them, especially in countries with transition economy with excess capacity and reduced fiscal space could be a good lesson for the Armenian government. For example, the Kyrgyz Republic for a country of its income level has a well-developed health information system that facilitated policy development, especially prospective provider reimbursement, based on enrollment at primary care facilities, hospital admissions, and outpatient utilization .A further important factor in the successful implementation of the reform process could be а high level of co-ordination and co-operation between the government and all the key international and bilateral donors working in the health sector in Armenia. This joined-up thinking will help ensure that improving access to health services remains at the centre of policy development.The article is written within the framework of the Armenian National Science & Education Fund (ANSEF) program.AMD, Armenian dram ; ANSEF, Armenian National Science & Education Fund; BBP, Basic Benefit Package; CIS, Commonwealth of Independent States; CE, Central Europe; CE/EECCA, Central Europe, Eastern Europe, the Caucasus and Central Asia; ECA, European and Central Asia; GDP, Gross Domestic Product; ILCS, Integrated Living Conditions Survey; MoF, Ministry of Finance; MoH, Ministry of Health; NSS RA, National Statistical Service of the Republic of Armenia; PHC, Primary Health Care; PHCR, Primary Health Care Reform; SHA, State Health Agency; SU, Soviet Union; UNESCO, United Nations Educational, Scientific and Cultural; UNICEF, United Nations International Children's Emergency Fund; USAID, United States Agency for International Development; WHO, World Health Organization; WB, World Bank; YSMU, Yerevan State Medical University.The authors declare that they have no competing interests.TT conceived the idea, collated, analyzed and summarized the data and wrote the paper. She was principal investigator of the study and drafts the manuscript. LM helped in collecting the data. Co-author read and approved the final manuscript.Tamara Tonoyan is a Ph.D. of Economics, Associate Professor of Health Economics at the Yerevan State Medical University (YSMU) after Mkhitar Heratsi and Head of the Department of Health Policy, Economics and International Relations at the National Institute of Health, Ministry of Health, Republic of Armenia (NIH MH RA).Lusine Muradyan is a Doctor of Medical Science, Associate Professor at the Yerevan State Medical University (YSMU) after Mkhitar Heratsi, Republic of Armenia.


Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia. We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn. Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies. Data extraction was completed independently by two reviewers. The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration. We included four trials; the quality of three was adequate. In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant. Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice. There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes. Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication. In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly. Intention to treat analyses should be used and interpreted appropriately. The mortality, morbidity and economic burden of Chronic Obstructive Pulmonary Disease (COPD) exacerbations is well documented -4. ReducIn light of the debate around the role of long term ICS in COPD , consideThe search strategy involved text words for COPD and the names of inhaled steroids used in COPD and relevant Medical Subject Headings (MeSH). Boolean logic was used to truncate and combine terms and the search strategy was modified several times before being finally performed (full search available from the authors). The Cochrane Library and the Database of Abstracts and Reviews were searched for existing systematic reviews on this topic. None were found so we searched for published original articles in PubMed, EMBASE and CINAHL from inception to February 2007. Criteria for the inclusion and exclusion of studies were based on the four facets: Population, Intervention, Comparison and Outcome. Studies were included if they were randomised controlled trials, comparing patients withdrawn from ICS with those not withdrawn, in which the diagnostic criteria for COPD were consistent with GOLD, NICE or ATS ,3,12. StTwo reviewers independently reviewed papers identified by the electronic search for potential inclusion on the basis of their titles and abstracts and independently scrutinised full texts of papers considered potentially includable to confirm inclusion/exclusion. Any discrepancies were resolved through discussion between the two reviewers. To identify further studies, we searched citations of included reports and contacted experts in the field. Data from each included trial were extracted independently by two reviewers. Again, disagreements were resolved through discussion. We extracted data on outcomes, the design and conduct of the trial, the way in which exacerbations were defined, the protocol for managing severe exacerbations, and the methodological quality of the trials.To assess quality we used the Cochrane collaboration classification scheme for assessing bias . We usedWe only conducted a meta-analysis on outcome data from trials which we rated as acceptable in terms of bias on at least three of the five bias criteria listed above, and only when relevant data could be obtained from at least three trials. For other outcomes we report results from individual trials. We meta-analysed outcome data using the random effects method of DerSimonian & Laird , with thThe electronic search identified 107 publications of which 103 were excluded on the basis of their titles and abstracts  days, P = 0.05) [Meta-analysis indicated that patients who had been withdrawn from ICS were slightly more likely to experience an exacerbation in the study period , but the effect was not statistically significant Figure . Statist = 0.05) . The mea = 0.05) . Change All three parallel trials -17 assesThere is no conclusive evidence from the trials included in our review that withdrawal of ICS has an effect on the frequency or number of exacerbations. Two trials showed a statistically significant decrease in the time to first exacerbation. Effects on other outcomes are inconclusive. These results are not inconsistent with a recent review in which the authors suggest that the benefits of ICS in preventing COPD exacerbations may be overstated .We conducted a robust systematic review. Nevertheless, we did not assess publications in languages other than English and, given the small number of studies identified, could not assess publication bias. Limited data within the trial reports meant that we were only able to conduct one meta-analysis.There are reasons for being cautious about the one meta-analysis we conducted and, in general, meta-analysing results from these types of trial. First, there are differences in patient characteristics between trials, in this case duration of use of ICS and exacerbation rate prior to entry to the trial which may be related to a patient's dependency on inhaled steroids, and differences in outcome definition, in this case definition of exacerbations Table . The twoWe recommend that authors make it clear in these trials what other medication patients were likely to have been taking during the trial period and whether there were differences between intervention and control, particularly in situations where the drug being withdrawn is generally seen as an add-on to other medication, as in the case of inhaled corticosteroids. In the COSMIC trial, all patients were prescribed a long acting bronchodilator as part of the trial. In the COPE trial, data on the use of rescue β2 agonists during the study were collected but not presented in the paper. In WISP it is reported that those in the placebo group used a reliever inhaler more frequently during the trial than those in the treatment group. No information is given in the O'Brien trial regarding other medications. Another factor that needs to be clearly reported is the length of time patients have been on inhaled corticosteroids prior to the start of the trial as this may influence the effect of withdrawal; two trials did not give any details of this.The differences between the trials in the treatment of those experiencing severe exacerbations highlight the need for clear reporting in this area. Currently there is no agreed classification of exacerbations . ProvidiA further issue that we became aware of in reviewing these trials is the description of those who discontinue randomised treatment. In the COSMIC trial these individuals were described as drop-outs, although they appeared to provide outcome measures. We suggest that these individuals would be better described as 'discontinuers' and those who do not provide outcome data described as drop outs from the trial. Using this terminology, there were no drop outs in the COSMIC or WISP studies, and only two (both deaths) in the COPE study. There were 134 discontinuers (51%) in the WISP study , 80 (21%) in COSMIC  and 32 (13%) in COPE . Furthermore, taking a pragmatic approach, which is necessary in these trials on ethical grounds, differences in discontinuation between groups are not of paramount importance in assessing the effect of withdrawal.How should the results of these trials be analysed and how should these analyses be interpreted? Intention-to-treat (ITT) is the recommended analysis for pragmatic superiority randomised controlled trials . Per proIn such trials, the ethical imperative to allow patients to discontinue randomised treatment and the fact that more in the placebo group usually do so, means that in a per protocol analysis there are likely to be more severely ill individuals in the group receiving ICSs. Thus a per protocol analysis will often underestimate the effect of the withdrawal of treatment on the target population as a whole, and its usefulness in trials at the explanatory end of the spectrum is diminished because an underestimate of effect might lead to treatment being withdrawn when in fact this withdrawal may be harmful. Intention-to-treat analyses make more sense in these trials, but should be interpreted in the context in which the trial is being undertaken. Given the potential differences between the management of patients in different trials, as illustrated in this paper, this interpretation may be unique to the context, and comparisons between different trial results should be made with caution.Whether there are more suitable analyses for trials in which treatment is withdrawn is an important question. For trials with binary outcomes, Graham Dunn developed a method of allowing for non-compliance while effectively keeping all individuals in an analysis thus overcoming one of the criticisms of per protocol analyses that the balance achieved by randomisation is broken . To our A further issue in relation to interpretation is the risk of bias introduced by unblinding of patients who have had an exacerbation severe enough to warrant a discontinuation of randomised treatment. It seems likely that there will be more of these patients in the placebo group and this may introduce performance bias.At the moment there are no national or international guidelines advocating the withdrawal of inhaled corticosteroids in those with COPD. Our review does not indicate that patients withdrawn from inhaled corticosteroids will, in general, have substantially worse outcomes than those not withdrawn. Nevertheless, we cannot advocate the withdrawal of inhaled corticosteroids in patients with COPD until further studies confirm which subsets of COPD patients benefit from this treatment and which subsets are at most risk of developing side effects.The withdrawal of ICS in patients with COPD may cause exacerbations sooner with a smaller effect on the number of exacerbations. Effects differ according to the definition of outcome and setting and management of patients within the trial. Clarity is needed in the reporting of these trials, particularly in defining exacerbations, reporting the management of exacerbations severe enough to warrant discontinuation of randomised treatment, the description of individuals who discontinue, and the collection and analysis of their outcomes. ITT analyses are appropriate for these trials, but other methods of analysis could be explored including analyses which attempt to identify those for whom discontinuation results in little in the way of detrimental effects.COPD: chronic obstructive pulmonary disease; ICS: inhaled corticosteroids; NICE: National Institute for Clinical Excellence; ATS: American Thoracic Society; GOLD: Global initiative for chronic obstructive pulmonary disease; COPE: Effects of discontinuing inhaled corticosteroids in patients with chronic obstructive pulmonary disease; COSMIC: COPD and Seretide: a multi-centre intervention and characterisation; WISP: Withdrawal of inhaled corticosteroids in people with COPD; SGRO: St George's respiratory questionnaire; FEV: forced expiratory volume.The authors declare that they have no competing interests.SE conceived the study. SE and NN designed the study. NN identified trials. All three authors assessed the quality of the trials. SE and NN extracted data from the trials. SE performed the meta-analysis. All three authors wrote and revised the manuscript.


Podoconiosis is one of the most neglected tropical diseases, which untreated, causes considerable physical disability and stigma for affected individuals. Little is known about the quality of life (QoL) of patients with podoconiosis. This study aimed to assess the QoL of patients with podoconiosis in comparison with healthy controls in Ethiopia.A comparative cross-sectional study was conducted in May 2012, among 346 clinically confirmed adult patients with podoconiosis, and 349 healthy adult neighbourhood controls in Dembecha woreda (district) in northern Ethiopia. QoL was assessed using the validated Amharic version of the World Health Organisation Quality of Life questionnaire (WHOQoL-BREF) scale; in addition, mental health and stigma were assessed by the Kessler-10 scale and podoconiosis stigma scale respectively. Logistic regression analysis was done to identify factors associated with QoL.Patients with podoconiosis had significantly lower mean overall QoL than the controls (52.05 versus 64.39), and this was also true in all four sub domains . Controls were 7 times more likely to have high (above median) QoL  than cases. Factors associated with lower QoL were: experiencing high levels of stigma, living in an urban area, being illiterate, having additional co-morbidities, and being unmarried. Mental illness was associated with lower scores in psychological and physical domains.Programs targeting podoconiosis interventions should include QoL as an indicator for monitoring progress. Interventions targeting improvement of QoL among patients with podoconiosis should address depression, stigma and other co-morbidities. Podoconiosis is a form of elephantiasis that predominantly affects barefoot subsistence farmers in areas with red volcanic soil . It has The disability and deformity caused by podoconiosis have been shown to have economic and social consequences ,12. ThesWHO defines Quality of Life as “individuals’ perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns” . This isIn a literature search, thirteen studies were found that assessed quality of life of patients with NTDs using standardised scales. One of these looked at dermatological quality of life in podoconiosis, and found a significant reduction in quality of life comparable to other dermatological conditions ; of the Overall, the review suggested that these NTDs have a significant impact on quality of life, no matter which of the assessment scales were used. However, few of the studies actually compared a patient group with healthy controls, so other factors might reduce the score for a community as a whole; having said this, those that did include controls tended to find worse quality of life in patients. Factors such as disability, deformity and discrimination, which have been found to increase the association between other NTDs and quality of life, are also found in podoconiosis. In addition, these studies consistently showed NTDs to exert the greatest effects in the physical and psychological domains.This review leads to the hypothesis that podoconiosis, in common with the other NTDs, will have a significant impact on the quality of life of sufferers. Whilst there has been one study of the impact of podoconiosis on dermatological quality of life , there iThe study took place in Dembecha woreda (district), part of the West Gojjam zone of Amhara regional state, northern Ethiopia, which has a population of 142,118. The woreda is split into 29 kebeles , of which 25 are rural and 4 are urban. Just 14% of the population live in urban areas. The largest ethnic group reported in Dembecha is Amhara (99.82%), and Amharic is spoken as a first language by 99.87%. The majority of the inhabitants of this region are Ethiopian Orthodox Christians (98.47%), while 1.46% are Muslim .Podoconiosis has been found to be prevalent in this area. In November 2011, a baseline survey prior to establishing a podoconiosis treatment service in the area screened 51,017 individuals and identified 1,704 new cases of podoconiosis . BetweenSeven kebeles within Dembecha woreda were selected for the study. These were chosen on the basis of having the highest prevalence of podoconiosis identified by the above survey, and so the largest possible patient population to sample. The study population constitutes those patients identified by the 2011 survey, and their neighbours without podoconiosis  and oversaw the data collection process; two of these  were fluent in Amharic. Each day the supervisors had contact with all the data collectors to answer any queries, and reviewed all of the questionnaires for missing data and inconsistencies. Questionnaires were returned for completion or correction if there were problems. In addition, supervisors checked the reliability of the data collectors by re-interviewing a number of participants. This found that the answers were broadly the same, and reliability of the data collection was not considered to be a problem.Data collection was carried over 5 days between 3Data analysis was done using SPSS-19. Data were first checked and cleaned, with missing values on the scales replaced with the average of that item. Five questionnaires were excluded because they were incomplete.2 test was used to establish significance; when comparing means, the independent t test was used to compare the mean differences in QoL level across groups. Mean scores of the overall QoL, and 4 sub-domains, were compared. Presence of mental disorder was based on the cut-offs outlined above.Descriptive analysis of the social demographic distributions and the degree of comparability of the case and control groups was done. When comparing simple frequencies, the chiLogistic regression was performed for total QoL, and for each of the physical and psychological sub-domains. For the quality of life scores, the median of each scale was calculated and used as a cut-off point between “High QoL score” and “Low QoL score”. The medians were 58.5, 57.2, and 58.3 for total QoL, physical and psychological sub-domains respectively. For each dependent variable, all the important variables were tested, and those with a significant association were included in multivariate analysis, in addition to variables shown previously to impact upon the dependent variable. This meant that occupation was excluded from all as being not significant, and living in either rural or urban areas was excluded from physical domain analyses. In addition, stigma was excluded from the multivariate analysis as it was only measured for cases and not controls.The reliability coefficients of the three scales and the correlation between the domains of the WHOQoL-BREF were also assessed.Ethical approval was sought and obtained from the Research Governance and Ethics Committee of Brighton and Sussex Medical School, and the Amhara Regional Health Bureau. Written informed consent was sought from all participants, with those who were unable to sign leaving a thumbprint instead. When individuals aged <18 years were encountered, consent was obtained from their parents or guardians. Data collectors were trained in key ethical issues, including how to ensure informed consent, as part of their initial briefing. All questionnaires were anonymised and identifiable information stored separately from the research data. Electronic data was kept on a password-protected computer.The groups were well matched on place of residence and were comparable in terms of gender and age Table . All thoPatients with podoconiosis had significantly lower mean overall QoL scores than the controls Table . The oveFactors significantly associated with quality of life are depicted in Table Mean scores on the WHOQoL-BREF showed some association with disease stage, decreasing as the disease became more advanced; however the pattern was not consistent as stage 4 had lower mean QoL scores than stage 5 Figure .All the tools were found to have good reliability, with Cronbach’s alpha of greater than 0.7. The Kessler, enacted stigma and overall QOL scales all showed excellent reliability, with a reliability coefficient exceeding 0.9 Table . The fouOn the basis of evidence from other NTDs and the previous study of dermatological quality of life it was hypothesised that podoconiosis would have a large negative effect on quality of life. The results of this study support this hypothesis, with significant differences seen between patients and controls in mean scores of all of the domains of quality of life, and show an association between podoconiosis and poor quality of life. The regression analysis also supported this conclusion, and showed that patients with podoconiosis have almost seven times the risk of healthy people for having a below average score on this scale. This is in accordance with the only other study of quality of life in podoconiosis, which demonstrated low dermatological quality of life among patients with podoconiosis . In addiThese results also fit well with what is known about other NTDs. When compared to the results of those studies that used the same scales, the impact of podoconiosis was found to be greater than other NTDs, particularly in the physical and social domains ,28,46,47Most of the factors associated with QoL were consistent with previous reports. These included experiencing high levels of stigma, living in an urban area, being illiterate, having additional co-morbidities, and being unmarried. In addition, the presence of a mental health disorder was found to reduce physical and psychological quality of life, and this has been found to be a consistent predictor of low QoL in many studies ,49. SimiThe study also found that the level of stigma experienced by patients increased and their QoL decreased as the disease stage became more severe. The most severe stages of podoconiosis are characterised by one or both of swelling above the knee and joint fixation in the feet, leading to greater physical disability and increased deformity. In addition to the physical limitations, these patients may experience more stigma and discrimination as they are easily identified. Similar findings have also been reported among patients with lymphatic filariasis and leprosy ,25.This study has several strengths. Firstly the study used validated instruments for measuring QoL, common mental disorders and stigma. Secondly the study included healthy controls against which to compare the QoL of patients with podoconiosis, which many of the previous studies in NTDs lack. Nonetheless the study is not without limitation. It could be argued that QoL is better measured qualitatively by exploring patients’ life experience and perceptions; however, as previous studies have documented the social exclusions and stigma faced by patients with podoconiosis, it was felt that the use of standardized tools to quantify the extent of QoL among patients with podoconiosis was a valuable addition to the evidence, and would enable direct comparison with other conditions. We did not measure the frequency of ‘acute attacks’ (variously termed acute adenolymphangitis or acute dermatolymphangioadenitis). Acute attack frequency appears to affect the QoL of patients with lymphatic filariasis, and might underlie some of the diminished life quality measured among patients with podoconiosis. Purposive sampling of the cases is also another limitation of the study. Nonetheless, more than 75% of the cases in the selected kebeles were included in the study.Taking into account the above limitations, the results have a number of implications for podoconiosis prevention and treatment programmes. This study is the first to demonstrate the effect of podoconiosis on general quality of life, adding urgency to the task of reducing the burden of podoconiosis in affected communities. Previous studies have documented the effectiveness of even three months of simple hygiene and bandaging treatment for patients with podoconiosis, which leads to physical improvement of the feet and legs, with decreased swelling and mossy lesions ,51. ThisIn conclusion, this study has demonstrated that patients with podoconiosis have significantly lower QoL than healthy controls, both in the overall score and all domains of QoL. It has also shown that patients with podoconiosis have lower mean QoL scores than those with other NTDs such as lymphatic filariasis and leprosy. This indicates that programs focusing on treatment of patients with podoconiosis should follow a holistic approach to address the psychological, social and environmental impact of the disease, not just the physical illness. Efforts to improve QoL of patients should give priority to those with advanced disease, those who are unmarried, those with co-morbidities and those with low literacy.The authors declare that they have no competing interests.EM, KD, GD conceived the study. EM, KD, AT conducted the field work. EM & KD conducted the analysis. EM, KD, AT and GD interpreted the findings. All authors read and approved the final manuscript.