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Introduction Access to Effective Antibiotics Resistance to antibiotics is increasing in a wide range of pathogenic bacteria, threatening the availability of effective antibiotics.1 Increasing rates of antimi- crobial resistance (AMR) are reported in all regions of the globe.2 This threat is partly attributed to the excessive use of antibiotics, since consumption has- tens the selective pressure on bacteria which results in the survival of resistant, and multi-resistant, strains.3 Moreover, antibiotic consumption is increasing glob- ally, with high levels of antibiotics prescribed unneces- sarily.4 Thus, making sure that existing antibiotics are used appropriately is fundamental.

Notwithstanding, access to life-saving antibiotics is inadequate in many parts of the world, especially in low- and middle-income countries.5 An estimated 5.7 million people die from treatable infectious diseases every year, surpassing the estimated 700,000 annual deaths due to AMR (which includes not only antibi- otic resistance but also antifungal, antiparasitic, and antiviral resistance).6 Therefore, measures to increase

access should be linked with proper control measures to ensure appropriate use. This has led to calls for anti- biotics, especially novel and specific last-resort antibi- otics, to be treated as a type of controlled medicines similar to the controlled drug regimen for narcotics with the intent being that these precious antibiotics can be safeguarded.7

The Current Drug Control System Three United Nations (UN) Conventions make up the current drug control regimen. The first conven- tion that was devised is the 1961 Single Convention on Narcotic Drugs, as amended by the 1972 Protocol, often referred to as the Single Convention. One hun- dred and eighty-six nations have officially ratified the Single Convention, making it one of the most widely adopted international legal instruments.8 The aim of the Single Convention is to achieve a “balanced policy” — in other words to prevent abuse as well as to ensure adequate access for sound medical practice (especially access to opioids for pain management). Provisions of the Single Convention are designed to fulfill these objectives, and include measures related to control- ling the production, manufacture, export, import, distribution, trade, cultivation, and possession of con- trolled medicines.

The Single Convention created a foundation for strict control over the consumption of narcotic drugs where all governments must provide annual estimates of their drug requirements and statistical returns on actual activities involving narcotics to the International Narcotics Control Board (INCB). All governments are obligated to comply with this system, including coun- tries that have not ratified the Single Convention. If countries require more than their annual estimates, they must request adjustments to their estimates. If

Should Antibiotics Be Controlled Medicines? Lessons from the Controlled Drug Regimen Live Storehagen, Friha Aftab, Christine Årdal, Miloje Savic, and John-Arne Røttingen

Live Storehagen, M.Pharm., M.Phil., is an advisor on global health and antimicrobial resistance for the Norwegian Institute of Public Health (NIPH) in Oslo, Norway. Friha Aftab, M.D., is working at the Oslo University Hospital, Nor- way. She wrote her dr.med. thesis on controlled medicines and antibiotic stewardship. Christine Årdal, Ph.D., is a senior advisor on global health and antimicrobial resistance for the Norwegian Institute of Public Health (NIPH) in Oslo, Nor- way. Miloje Savic, Ph.D., is a senior advisor on global health and antimicrobial resistance for the Norwegian Institute of Public Health (NIPH) in Oslo, Norway. John-Arne Røttin- gen, M.D., Ph.D., M.Sc., M.P.A., is the Chief Executive of the Research Council of Norway and Adjunct Professor at the Department of Global Health and Population, Harvard T.H. Chan School of Public Health.

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the annual estimates are exceeded and not adjusted, these are deducted from the estimates for the follow- ing year. Exporting countries are obliged to limit sales to the quantities remaining with the annual national estimates.9 The Single Convention also introduced a drug classification system where narcotic drugs are classified in four schedules according to dependence potential, abuse liability and therapeutic usefulness (Table 1). The different schedules are subject to differ- ent “degrees of control”. It ranges from most restrictive to least restrictive in this order: Schedule IV, Sched- ule I, Schedule II, and Schedule III. The INCB pub- lishes annually a list of narcotic drugs under interna- tional control, which contains more than one hundred substances.10

A decade after the introduction of the Single Con- vention, the 1971 Convention on Psychotropic Sub- stances was developed. This Convention expanded the range of drugs to include synthetic drugs, but imposed a weaker control system compared to nar- cotics. In 1988, in response to the rapidly growth of the illicit drug trafficking market, the Convention against Illicit Traffic in Narcotic Drugs and Psycho- tropic Substances was adopted.11 Yet, despite the exis- tence of these widely adopted conventions, abuse of narcotics continue to be a major problems, with the United States (US) recently declaring it a “public health emergency.”

Methods The aim of this qualitative study was to evaluate the applicability of the current controlled drug regimen for ensuring appropriate use of antibiotics. The study was guided by the following research questions:

1. What are the measures embedded in the Single Convention, and which could be applicable in the area of ensuring appropriate use of antibiotics?

2. How successful in general have these measures (identified in the first research question) been to control opioid use and to ensure access for medi- cal purposes?

3. What can be learned from the measures and interventions implemented in different coun- tries’ regulatory systems as a result of the Single Convention?

A content analysis of the Single Convention was con- ducted in order to identify all the measures embed- ded in it designed to prevent abuse or ensure avail- ability (research question 1). The identified measures were then classified into different categories. Next we decided on the categories of measures relevant to include in our analysis for their applicability to antibi- otics. For the measures assessed as “possibly relevant,” we identified similar measures already in existence for antibiotics.

Classification of Narcotics Definition

Examples (Cited from the 56th Edition of the INCB’s “Yellow List” – List of Narcotic Drugs under International Control)

Schedule I Substances that are highly addictive and liable to abuse, or are convertible into drugs that are similarly addictive and liable to abuse.

Methadone, morphine and other strong opioids.

Schedule II Substances that are less addictive and liable to lesser abuse than Schedule I.

Codeine.

Schedule III Preparations containing narcotic drugs intended for medical use and are unlikely to be abused. These are exempt from certain provisions, e.g. trade authorizations, estimates of need and statistical returns to the Board.

Preparations of codeine and ethyl morphine (when containing not more than 100 milligrams per dosage unit and with a concentration of not more than 2.5 per cent in undivided preparations).

Schedule IV Selected substances in Schedule I that are particularly harmful in terms of addictive properties and abuse potential, and are rarely used in medical practice. All Schedule IV drugs must also be in Schedule I, and countries can choose to prohibit these substances.

Heroin and cannabis.

Table 1 Classification of Narcotics, Adapted from the INCB’s Training Material for the International Control System for Narcotic Drugs

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To answer research questions 2, we did a literature review using the PubMed database. We searched for articles published between 2007 and July 2017 using the search terms “opioids,” “drug and narcotic control,” “opioid-related disorders,” and “access” or “availabil- ity”. Only articles published in English were included. References were checked for additional materials. Then, eight semi-structured interviews were con- ducted to provide examples of the challenges and best practices for ensuring appropriate access to opioids within different countries (research question 3). We interviewed government officials or private sector representatives from Brazil, Finland, India, Mexico, Norway, Singapore, and Uganda — selected to rep- resent different country income groups and different consumption levels of opioids. We also interviewed an international drug control expert. Findings from the literature review were also used to support the results from the interviews. Finally, we combined the findings from all of the three research questions to derive on our recommendation regarding which measures could be applicable to ensure appropriate use of antibiotics.

Results and Discussion Has the Single Convention Ensured a Balance between Access and Control? The international drug control system has been criti- cized for having had negative effects on public health. WHO estimates that 5.5 billion people have low to non- existent access to treatment for moderate to severe pain despite the growing burden of cancer.12 In our lit- erature review we found several research articles high- lighting that access to opioids for pain management is inadequate in most parts of the world, especially in Africa and Southeast Asia. In sub-Saharan Africa, it is estimated that 88% of cancer deaths are untreated for cancer pain.13 In India only 0.4% of more than a million people who need opioids for pain relief have access.14 However, the global opioid consumption for pain treatment has more than doubled between 2001- 03 and 2011-13, but this increase is concentrated in a few high-income countries. North America (the US, Canada and Mexico), Australia, and some western and central European countries account for 95.7% of the world’s opioid consumption, but represent only 15% of the world’s population.15

The reasons for low access to opioids are multifacto- rial. First, many governments have not focused on the “access” aim of the Single Convention. Regulations to reduce abuse have obstructed actions to ensure avail- ability for medical purposes. Several national laws lack provisions to ensure adequate access for medical and scientific purposes. In addition, the UN model laws that are used by governments to draft national legisla-

tion have not included an obligation for governments to ensure availability of narcotics for medical use, but rather focused exclusively on the abuse potential.16 Other factors, such as the international trade controls, fears of addiction, lack of training for medical profes- sionals and public awareness, and excessive regulatory measures related to the prescribing and dispensing of opioids are causing the low access to pain treatment.17 These factors were also highlighted in our interviews, and are discussed in the following sections.

Despite the stringent control measures introduced by the Single Convention, overuse of controlled drugs has reached alarming levels in some high-income countries. It is estimated that there are 15.5 mil- lion opioid-dependent people globally.18 The US has recently experienced significant increases in morbid- ity and mortality associated with the overuse of opi- oids,19 and the non-medical use of prescription opioids has reached epidemic proportions.20

It is apparent that governments around the world have struggled at achieving a balanced policy that prevents drug abuse while at the same time ensures availability for medical purposes. Moreover, the con- trol system put in place by the Single Convention is blamed for causing additional detrimental effects on public health, such as contributing to the spread of communicable diseases like HIV and exacerbating the overdose problem.21

Measures in the Single Convention and Their Applicability to Antibiotics For the purposes of this study, we further examined the specific components of the Single Convention and assessed the evidence of their effectiveness. In our content analysis of the Single Convention we identi- fied thirty-five measures that we categorized into eight categories:

• Drug classification system • Prescribing and dispensing • Consumption control and monitoring • Licenses • Drug control organs • Government obligations and rights • Illicit activities and abuse • Measures specific to opium, cannabis and coca

leaf

The detailed categories and underlying measures are listed in Supplementary Table 1. From these categories we excluded the last four in the above mentioned list because the measures were related to providing the legal framework for countries to organize the imple- mentation of the Single Convention at the national

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level, thus not directly specific to the drug control regimen (“drug control organs” and “government obli- gations and rights”) or the measures were of less rel- evance for antibiotics (“illicit activities and abuse” and “measures specific to opium, cannabis and coca leaf ”). This is not to say that illicit activities and abuse are not at all relevant for antibiotics, but it is within the larger context of counterfeiting which is not antibiotic specific. We then assessed how successful underly- ing measures have been to control opioid use and to ensure access for medical purposes. In Table 2 we list them, comment on their applicability to antibiotics, and summarize the main findings from the interviews and literature review. The following sections describe our findings in greater detail, and include examples and lessons learned related to how these measures are implemented in different countries’ national systems. We also discuss how each of the previously mentioned categories of control measures may, or may not, apply to antibiotics.

Drug Classification System The classification system in the Single Convention serves as a model for national scheduling systems. This means that drugs included in different national control legislations do not necessarily exactly match the scheduling of drugs according to the Single Con- vention. Accepting the treaty means that the country has to implement the treaty as a domestic law, which can be stricter than the treaty.22 As a consequence, some countries incorporate control measures required only for Schedule I drugs over narcotics in Schedule II, prohibit certain narcotics, or implement additional regulatory measures not required by the Single Con- vention. Moreover, the Single Convention leaves some room for interpretation when formulating domestic laws. For example, national laws on the possession of cannabis vary between countries. It is illegal in most countries, but in some countries medical cannabis is available and recreational use is accepted, such as in the Netherlands. In the US, cannabis is illegal for both medical and recreational purposes by the federal law,

but not necessarily by state laws. The US government simply has chosen not to prosecute federal law viola- tions related to cannabis, as long as they comply with the local law.

Overuse of narcotics is a global concern due to the abuse potential, whereas overuse of antibiotics is a global concern due to the emergence of resistance. A classification system for antibiotics, similar to the one embedded in the Single Convention, therefore appears as a useful mechanism for identifying those critical antibiotics that should be used sparingly. It might facilitate conservation efforts that could be harmonized across multiple countries, if not globally. This may include limiting which physician specialities are allowed to prescribe selected antibiotics, in what settings they are used, how use is monitored, require- ments for strict infection control measures, restricting manufacturers’ ability to promote certain antibiotics, and AMR surveillance requirements. However, the WHO has already introduced a classification system

for antibiotics. In 2015, the WHO introduced the list of Critically Important Antimicrobials (CIA). This list ranks antimicrobials according to their importance to human medicine: critically important, highly impor- tant, and important. The purpose of the CIA list is to reduce the use of antimicrobials in food animals, particularly those antimicrobials that are critically important for human medicine.23 Moreover, the latest edition of the WHO essential medicines list includes a classification system where antimicrobials are placed in three different tiers: access, watch and reserve.24 The “access” group includes antibiotics, like amoxi- cillin, that should be readily available for common infections. The “watch” group contains antibiotics that should be used sparingly for a small number of infections. This group contains first- or second-choice drugs like ciprofloxacin. Lastly, the “reserve” group contains the “last resort” antibiotics that should be used only for specific patients and settings or to treat life-threatening infections due to multidrug-resistant bacteria like, colistin and new-generation cephalo-

Overuse of narcotics is a global concern due to the abuse potential, whereas overuse of antibiotics is a global concern due to the emergence of resistance.

A classification system for antibiotics, similar to the one embedded in the Single Convention, therefore appears as a useful mechanism for identifying those

critical antibiotics that should be used sparingly. It might facilitate conservation efforts that could be harmonized across multiple countries, if not globally.

Storehagen et al.

Table 2 Control Measures in the Single Convention: Assessment of Applicability, Measures Already in Existence for Antibiotics and Main Findings from Interviews and Literature Review

Measure Applicable to Antibiotics?

Measures for Antibiotics to Achieve the Same Intent

Main Findings from Interviews and Literature Review

Drug Classification System

Controlled substances are placed in different schedules (Schedule I-IV) according to their abuse potential and are under different degree of control. Schedule I drugs are subject to all applicable measures.

Possibly WHO’s Essential Medicines List (EML revision May 2017 classified essential antibiotics into 3 categories). WHO’s Critically Important Antimicrobials.

- Flexibility exists when developing national legislations. - Many countries have implemented regulatory measures not required by the Convention or made domestic law stricter.

The Commission on Narcotic Drugs (CND), based on recommendation by the WHO, may amend the drug classification list. A state may propose amendments to the lists.

Possibly

Prescribing and Dispensing

A medical prescription is required for the supply or dispensation of drugs to individuals for Schedule I drugs.

Possibly National regulations. AMR action plans. WHO guidance.

- Additional regulatory control measures implemented by several countries (e.g. limited prescription rights and limited validity of the prescription). - Education and training is essential for adequate pain management. - Fear of prescribing and stigma have contributed to low access to opioids. - Some countries use special prescription forms/ systems.

If deemed necessary, countries may require that prescriptions for Schedule I drugs are written on official forms to be issued in the form of counterfoil books by the government or authorized professional associations, and be kept for a period of not less than two years.

Possibly

Governments may choose to regulate the packaging of medicines (a clearly visible double red band on the inner package containing a drug or wrapping thereof).

Possibly

International Consumption Control and Monitoring

Governments must provide annual estimates to the International Narcotics Control Board (INCB) of the quantities of controlled drugs needed for medical and scientific purposes, quantities needed for manufacturing and quantities needed for special stocks.

Possibly Currently forecasting of expected consumption of antibiotics is performed by some procurement systems, but not as a function of the optimal societal use.

- Governments use different methods for providing estimates. - Not all governments provide estimates of their annual need and the statistical returns on actual consumption as required. - Some governments lack the expertise and resources to make accurate estimates and instead make slight adjustments to the previous year’s numbers. - Many countries provide too low estimates. - Border control of import/ export works well (not many countries exceed their limits).

The INCB shall examine the government estimates and supplementary estimates and as expeditiously as possible confirm these estimates. In cases of disagreements, the INCB has the right to create its own estimates. If any government fails to provide estimates, the INCB will establish the estimates, preferably in co-operation with the government concerned.

Possibly

Continued on p. 82

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Measure Applicable to Antibiotics?

Measures for Antibiotics to Achieve the Same Intent

Main Findings from Interviews and Literature Review

International Consumption Control and Monitoring Continued

If the annual requirements for consumption change, the government may submit supplementary estimates to the INCB.

No, this may delay access to life-saving medicines

Governments must on an annual basis report to the INCB on the amounts consumed and amounts used for the production or manufacture of drugs. Governments must every quarter report on the amounts of drugs imported and exported.

Possibly WHO programme on surveillance of antimicrobial consumption. The European Surveillance of Antimicrobial Consumption programme (ESAC). National surveillance systems for antibiotic resistance. Yet, no surveillance on antibiotic manufacturing to our knowledge.

Governments must report on seizures and stocks as of 31 December.

Possibly

The INCB shall examine the statistical returns with a view to determining whether governments comply with the provisions of the Single Convention, and may require further information if considered necessary.

Possibly Does not exist today to our knowledge.

The total quantities of each drug manufactured and imported must be within the limit of the country’s estimated requirements.

No, this may delay access to life-saving medicines

If the quantity manufactured and imported in any one year exceeds the country’s estimated requirements, this shall be deducted from the required estimates in the following year.

No, this may delay access to life-saving medicines

If the quantity exported to any country exceed the total of the estimates for that country, further exports authorizations shall not be authorized to that country (except under certain circumstances).

No, this may delay access to life-saving medicines

Records of manufacture, acquisition and disposal for each individual drug are to be kept by governmental authorities, manufacturers, traders, scientific institutions and hospitals. Such records shall be preserved for a period of not less than two years.

Possibly Does not exist today to our knowledge. However, some countries have good electronic systems for sales data at the retail level.

Table 2 (continued) Control Measures in the Single Convention: Assessment of Applicability, Measures Already in Existence for Antibiotics and Main Findings from Interviews and Literature Review

See previous page.

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sporins. This is the group of antibiotics where a legal classification system could be useful in the sense that it would put strict regulations on access, use and monitoring. So the question is: how could the accep- tance and adherence to this classification system be improved through a set of binding measures? We first examine the potential through controls on prescribing and dispensing.

Prescribing and Dispensing The only mandatory control measure in the Single Convention related to the dispensing of narcotics is to require a medical prescription for Schedule I narcotics when dispensing to individuals. In addition, the Single Convention suggests some additional measures gov- ernments can implement if deemed necessary (Table 2). However, despite the fact that the Single Convention does not dictate strict control related to the prescribing and dispensing of narcotic drugs, governments around the world have implemented stricter procedures in their national policies and legislations, attributed as

a consequence of the actual or perceived increase of misuse and dependence upon opioids.25 There are several examples of such additional regulatory mea- sures. For example, many countries have restricted the prescribing privileges to limited physician specialties, have complicated reporting or administrative require- ments when prescribing opioids, require special pre- scription forms and/or operate with a limited validity for opioid prescriptions.26 Furthermore, pharmacists usually have limited authority to correct minor errors on opioid prescriptions and prescribing for emergency use via phone or fax is usually not possible or at least restricted.27

These extra regulatory measures have been blamed for contributing to the low access rates to opioids for pain relief observed in many parts of the world. For example, India has had severely low opioid consump- tion for decades, with little increase in consumption even though the country has developed both economi- cally and in terms of health care.28 India implemented complex and strict regulations over the prescribing

Table 2 (continued) Control Measures in the Single Convention: Assessment of Applicability, Measures Already in Existence for Antibiotics and Main Findings from Interviews and Literature Review

Measure Applicable to Antibiotics?

Measures for Antibiotics to Achieve the Same Intent

Main Findings from Interviews and Literature Review

Licenses

Import and export licenses are required for each international transaction.

Possibly Most governments already require that activities related to pharmaceuticals are conducted under licenses, but do not require licenses for each import/ export.

- Multiple agencies involved in import/export authorizations. - Limited number of pharmacies have license to dispense opioids. - Limited number of manufacturers with licence to manufacture opioids.

All persons and enterprises involved in the manufacture, trade, distribution, import or export of drugs must be controlled under government license (except when carried out by a state enterprise).

Possibly

All persons who obtain government licenses must have adequate qualifications for effective and faithful execution of laws and regulations enacted to implement the Single Convention.

Possibly

Governments shall require that the drug labels show the exact drug content by weight and percentage for Schedule I drugs (not required when dispensed to an individual on medical prescription).

No, this measure is primarily intended to facilitate trade control function of custom officials, thus of less relevance for antibiotics.

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and sale of opioids under the introduction of the 1985 Narcotic Drugs and Psychotropic Substances (NDPS) Act, designed to fulfil India´s obligation under the Single Convention. The strict regulations led to stigma and negative attitudes, resulting in a fear of both stocking and prescribing opioids.29 The Act was last amended in 2014 to simplify opioid regulations, but there are concerns related to unintended effects.30

A number of control mechanisms have also been implemented in Brazil, including special color-coded prescription forms for different medicines. Physicians receive a set number of these prescription forms, with a lesser amount of the form designated for controlled medicines. Brazil has also implemented an electronic system where physicians’ prescribing habits can be monitored. According to our stakeholder interviews, this system has reportedly reduced the number of pre- scriptions for controlled medicines.

Even though some of these extra control measures have unintentionally served as a barrier for legitimate access for medical purposes, some of these measures could have merit in a stewardship framework for anti- biotics. We suggest examples in Table 3. Norway has recently implemented a warning in the clinicians’ pre- scriptions system that gives an alert when the clini- cian prescribes a broad-spectrum antibiotic. Norway is also looking at implementing other interventions, such as a limited prescription validity for antibiot- ics.31 Yet, these measures are dependent upon not only effective healthcare systems, but also the universal use of information technology. Therefore, the ability to implement these controls will vary greatly by country and within countries.

The dispensing of antibiotics without a prescription is a widespread practice.32 This is especially true in low-

and middle-income countries where laws restricting this practice may be in place, but enforcement mea- sures are lacking and access to qualified healthcare personnel is insufficient.33 In addition, internet ven- dors provide worldwide access to antibiotics, also for the population in countries with strict regulations.34 Could a binding agreement like the Single Convention reduce non-prescription use of “watch” and/or “last resort” antibiotics?

As we see from our analysis of the Single Conven- tion, it does not ensure that the right patients are receiving appropriate palliative care. The Single Con- vention provides a crude limit on the total national consumption of a specified narcotic, but does not include measures that facilitate appropriate use for the patients in need. Antibiotic stewardship aims to ensure that the right patient receives the right anti- biotic in the right dose at the right time. To achieve this, stewardship needs to be built into community and hospital-based routines. This is being increasingly implemented through AMR National Action Plans, with more and more WHO Member States publish- ing their plans.35 There is also some evidence that these stewardship efforts are succeeding in reducing antibiotic prescribing, including prominently broad- spectrum antibiotics.36

International Consumption Control and Monitoring According to the INCB’s annual report from 2015 excess imports or exports of narcotics occurred in only four countries. However, not all governments pro- vide estimates of their annual need and the statistical returns on actual consumption as required. 70% sub-

Table 3 Control Measures Identified in Countries Regulatory Systems Related to the Prescribing of Narcotics That May Have Merit for Regulating the Prescribing of Antibiotics

Control Measure Identified for Narcotics Implementation for Antibiotics Desired Outcome(s)

Limited prescription validity. Antibiotics prescribed to patients for self-treatment of common infectious diseases.

Avoid self-medication for future conditions and avoid misuse.

Limited prescribing rights (e.g. to selective medical doctors and/or infectious disease specialities).

Broad spectrum intravenous antibiotics and/or last resort antibiotics.

Avoid unnecessary use of medically important antibiotics. Ensure access to effective antibiotics for multi-resistant infections.

Implementing special prescription forms for antibiotics.

All antibiotics. Monitor use. Warning signal for the prescriber and the patient.

Storehagen et al.

mitted their requirements for 2016, while 63% pro- vided the Board with annual statistical reports.37

However, being able to identify the actual require- ments is a challenging task for many governments as they lack the expertise and resources needed to make accurate estimates.38 For example, several countries in Sub-Saharan Africa provide annual opioid estimates sufficient to treat only a handful of cancer patients.39 From our interviews, we understand that countries use different methods and data sources to make their estimates, and that oftentimes the estimates are merely slight adjustments to the previous year’s num- ber. In recent years, INCB and WHO have published guidelines to help governments to provide adequate estimates,40 but the impact is yet unclear.

Notwithstanding, the surveillance data provided by the Single Convention are enviable. Such data within an antibiotic context would be very beneficial for understanding the spread of antimicrobial resistance. Yet, surveillance data regarding antibiotic consump- tion and resistance levels are improving through sig- nificant national and multi-national efforts. WHO has recently launched a program on surveillance on anti- biotic consumption, as a result of the adoption of the

Global Action Plan (GAP), to assist countries to inte- grate surveillance of antimicrobial use into national programs. It provides a common methodology for the measurement of antimicrobial consumption that will allow for the monitoring of trends and comparison between countries at the global level.41 Europe has already implemented a program for sharing and com- paring information about antimicrobial consumption, the European Surveillance of Antimicrobial Con- sumption (ESAC). The network is coordinated by the European Centre for Disease Prevention (ECDC), and collects data from both the hospital and the commu- nity sector.42 The Fleming Fund is investing GBP 195 million in improving antibacterial surveillance capac- ity in low- and middle-income countries.43

Requesting countries to estimate antibiotic needs and reflect upon appropriate consumptions levels

would be a useful exercise for countries to explore areas where responsible use policies could be improved. Unfortunately, as mentioned previously, the estimates are often simple adjustments to the previous year’s number, thus lacking credibility.

Licenses The Single Convention requires a license for each international transaction (i.e. import and export) involving narcotics (Table 2). Again, some countries go beyond the Single Convention requirement. For example, India implemented a complex system for import/export following the 1985 Act, where a licence was required for each import/export also between states and with multiple agencies involved in the licensing process. The rules have been changed under the new law with the hope that opioids will be more available for medical purposes. Singapore limits the number of licenses for manufacturing opioids to a few companies. This way the government can better exer- cise control over the opioid market.

Licenses may also regulate where opioids can be dis- pensed. In several countries in Asia and Africa opioids can only be dispensed at hospital pharmacies.44 Simi-

lar restrictions exist also in parts of Eastern Europe. The utmost example is probably from Georgia where opioids can only be dispensed through special phar- macies placed in police stations.45

Controlling the international transactions of anti- biotics by requiring a license for each import/export, like the Single Convention, appears excessive. We cannot see how such trade-related restrictions will support the responsible use of antibiotics. Moreover, considering that adequate access to antibiotics is still a major problem in low- and middle-income coun- tries, imposing such control mechanisms could result in an increase of preventable deaths. Yet, there may be other areas related to the trade of antibiotics where the inclusion of international binding requirements could be applicable: (1) the issue of environmental pollution through pharmaceutical waste manage-

Whereas there may be specific AMR provisions that may be appropriate for a convention (e.g., ban on use of antibiotics for livestock growth

promotion), we do not see the Single Convention as a suitable model for the reasons stately previously. Rather it would be more effective to identify the specific gaps in control and oversight and determine if there is general

agreement and that no other tool can effectively remedy these gaps.

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ment of antibiotics, and (2) the use of antibiotics in agriculture.46

Can a Convention Regarding AMR Help to Enforce Global Norms? Tackling the global challenge of AMR has already become an urgent priority. The World Health Orga- nization (WHO) developed the Global Action Plan (GAP) on AMR in 2015.47 In 2016, the General Assem- bly of the UN adopted a political declaration on AMR reaffirming the need for coordinated action across sectors and launched the Interagency Coordination Group on AMR.48 Following this, the G20 Health Ministers made a declaration for enhanced response on antimicrobial resistance (the Berlin Declaration).49 The G20 has launched a multi-national AMR R&D Collaboration Hub. Twenty-six countries have joined forces in the Joint Programming Initiative on AMR.

A convention is one of the most stringent multilat- eral instruments for policymaking. Adopting a con- vention requires near-global consensus regarding important and unvarying norms. To be successful, effective enforcement mechanisms must be built in. Whereas there may be specific AMR provisions that may be appropriate for a convention (e.g., ban on use of antibiotics for livestock growth promotion), we do not see the Single Convention as a suitable model for the reasons stately previously. Rather it would be more effective to identify the specific gaps in control and oversight and determine if there is general agreement and that no other tool can effectively remedy these gaps.

Conclusion A globally agreed system for controlling antibiotic consumption, similar to the current drug control regi- men for narcotics, would allow for stringent controls on sale and consumption. This has been put forth as a possible mechanism to ensure tighter controls over critical antibiotics. We have identified components of the controlled drug regime that may be useful to consider also for antibiotics. However, we believe a similar system would detrimentally inhibit access, be costly and challenging to implement, and end up no more effective than introducing national stewardship measures already included in many countries’ national AMR plans. The challenge, though, is to find mecha- nisms for accountability. Based upon countries’ abil- ity to effectively implement their national AMR plans, new accountability mechanisms may be needed.

Note The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant

agreement n°115618 [Driving re-investment in R&D and responsi- ble antibiotic use — DRIVE-AB — www.drive-ab.eu ], resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution. This work does not necessarily represent the view of all DRIVE-AB partners. This work was also supported by the Research Council of Norway through the Global Health and Vaccination Programme (GLOBVAC), project number 234608.

References 1. C. L. Ventola, “The Antibiotic Resistance Crisis: Part 1:

Causes and Threats,” Pharmacy and Therapeutics 40, no. 4 (2015): 277-283.

2. World Health Organization, Antimicrobial Resistance: Global Report on Surveillance, available at <http://www.who.int/ drugresistance/documents/surveillancereport/en/> (last vis- ited April 2, 2018).

3. B. G. Bell et al., “A Systematic Review and Meta-analysis of the Effects of Antibiotic Consumption on Antibiotic Resis- tance,” BMC Infectious Diseases 14, no. (2014): 13.

4. K. E. Fleming-Dutra et al., “Prevalence of Inappropriate Anti- biotic Prescriptions among US Ambulatory Care Visits, 2010- 2011,” JAMA 315, no. 17 (2016): 1864-1873.

5. M. Mendelson et al., “Maximising Access to Achieve Appro- priate Human Antimicrobial Use in Low-Income and Mid- dle-Income Countries,” The Lancet 387, no. 10014 (2016): 188-198.

6. N. Daulaire et al., “Universal Access to Effective Antibiotics Is Essential for Tackling Antibiotic Resistance,” Journal of Law, Medicine & Ethics 43, Suppl. 3, no. (2015): 17-21.

7. S. J. Hoffman et al., “An International Legal Framework to Address Antimicrobial Resistance,” Bulletin of the World Health Organization 93, no. 2 (2015): 66; C. Årdal et al., “International Cooperation to Improve Access to and Sustain Effectiveness of Antimicrobials,” The Lancet 387, no. 10015 (2016): 296-307.

8. United Nations Treaty Collection, Status of Treaties: Chapter VI Narcotic Drugs and Psychotropic Substances, available at <https://treaties.un.org/pages/viewdetails. aspx?src=treaty&mtdsg_no=vi-18&chapter=6&lang=en> (last visited April 2, 2018).

9. United Nations. Single Convention on Narcotic Drugs (1961). 10. International Narcotics Control Board, Training Material:

1961 Single Convention on Narcotic Drugs. Part 1: The Inter- national Control System for Narcotic Drugs (2005), available at <https://www.incb.org/documents/Narcotic-Drugs/Train- ing-Materials/English/PART_I_English.pdf> (last visited April 2, 2018).

11. M. Jelsma, The Development of International Drug Control. Lessons Learned and Strategic Challenges for the Future: Series on Legislative Reform of Drug Policies, No. 10 (March 2011), available at <https://www.tni.org/files/download/ dlr10.pdf>.

12. World Health Organization, Access to Controlled Medica- tions Programme. Improving access to medications controlled under international drug conventions. Briefing note., avail- able at <http://www.who.int/medicines/areas/quality_safety/ ACMP_BrNote_Genrl_EN_Apr2012.pdf> (last visited 1 July 2016).

13. M. O’Brien et al., “Improving Access to Analgesic Drugs for Patients with Cancer in Sub-Saharan Africa,” The Lancet Oncology 14, no. 4 (2013): e176-182.

14. B. Larance et al., “The Availability, Diversion and Injection of Pharmaceutical Opioids in South Asia,” Drug and Alcohol Review 30, no. 3 (2011): 246-254.

15. S. Berterame et al., “Use of and Barriers to Access to Opioid Analgesics: A Worldwide, Regional, and National Study,” The Lancet 387, no. 10028 (2016): 1644-1656.

16. S. A. Husain et al., “Do National Drug Control Laws Ensure the Availability of Opioids for Medical and Scientific Pur-

Storehagen et al.

poses?” Bulletin of the World Health Organization 92, no. 2 (2014): 108-116.

17. See Berterame et al., supra note 15. 18. L. Degenhardt et al., “The Global Epidemiology and Burden

of Opioid Dependence: Results from the Global Burden of Disease 2010 Study,” Addiction 109, no. 8 (2014): 1320-1333.

19. A. Kolodny et al., “The Prescription Opioid and Heroin Cri- sis: A Public Health Approach to an Epidemic of Addiction,” Annual Review of Public Health 36 (2015): 559-574.

20. J. M. Tetrault and J. L. Butner, “Non-Medical Prescription Opioid Use and Prescription Opioid Use Disorder: A Review,” Yale Journal of Biology and Medicine 88, no. 3 (2015): 227-233.

21. J. Csete et al., “Public Health and International Drug Policy,” The Lancet 387, no. 10026 (2016): 1427-1480.

22. See United Nations, supra note 9. 23. World Health Organization, WHO List of Critically Impor-

tant Antimicrobials (CIA), available at <http://www.who. int/foodsafety/areas_work/antimicrobial-resistance/cia/en/> (last visited April 2, 2018).

24. World Health Organization, WHO Model Lists of Essential Medicines, available at <http://www.who.int/medicines/pub- lications/essentialmedicines/en/> (last visited April 2, 2018).

25. L. Manchikanti et al., “Current State of Opioid Therapy and Abuse,” Current Pain and Headache Reports 20, no. 5 (2016): 1-9.

26. L. Linge-Dahl et al., “Identification of Challenges to the Availability and Accessibility of Opioids in Twelve Euro- pean Countries: Conclusions from Two ATOME Six-Country Workshops,” Journal of Palliative Medicine 18, no. 12 (2015): 1033-1039.

27. N. I. Cherny et al., “Formulary Availability and Regulatory Barriers to Accessibility of Opioids for Cancer Pain in Europe: A Report from the ESMO/EAPC Opioid Policy Initiative,” Annals of Oncology 21, no. 3 (2010): 615-626.

28. J. Cleary et al., “Formulary Availability and Regulatory Bar- riers to Accessibility of Opioids for Cancer Pain in India: A Report from the Global Opioid Policy Initiative (GOPI),” Annals of Oncology 24, Suppl. 11, no. (2013): xi33-xi40.

29. M. R. Rajagopal and D. E. Joranson, “India: Opioid Availabil- ity. An Update,” Journal of Pain and Symptom Management 33, no. 5 (2007): 615-622.

30. G. P. Dureja et al., “Addressing the Barriers Related with Opi- oid Therapy for Management of Chronic Pain in India,” Pain Management 7, no. 4 (2017): 311-330.

31. Helse- og omsorgsdepartementet, Handlingsplan mot anti- biotikaresistens i helsetjenesten, available at <https://www. regjeringen.no/contentassets/915655269bc04a47928fce917e 4b25f5/handlingsplan-antibiotikaresistens.pdf> (last visited April 2, 2018).

32. D. J. Morgan et al., “Non-prescription Antimicrobial Use Worldwide: A Systematic Review,” The Lancet Infectious Dis- eases 11, no. 9 (2011): 692-701.

33. M. Ocan et al., “Household Antimicrobial Self-Medication: A Systematic Review and Meta-analysis of the Burden, Risk Factors and Outcomes in Developing Countries,” BMC Public Health 15 (2015): 742.

34. A. G. Mainous, 3rd, et al., “Availability of Antibiotics for Pur- chase without a Prescription on the Internet,” The Annals of Family Medicine 7, no. 5 (2009): 431-435.

35. World Health Organization, Antimicrobial Resistance. National Action Plans, available at <http://www.who.int/ antimicrobial-resistance/national-action-plans/en/> (last vis- ited April 2, 2018).

36. Blue Cross Blue Shield, The Health of America Report. Antibi- otic Prescription Fill Rates Declining in the U.S. (2017), avail-

able at <https://www.bcbs.com/sites/default/files/file-attach- ments/health-of-america-report/HoA.Antibiotics.Report. pdf> (last visited April 2, 2018).

37. United Nations: International Narcotics Control Board, Report of the International Narcotics Control Board for 2015 (January 2016), available at <https://www.incb.org/ documents/Publications/AnnualReports/AR2015/English/ AR_2015_E.pdf> (last visited April 2, 2018).

38. S. Dalal and E. Bruera, “Access to Opioid Analgesics and Pain Relief for Patients with Cancer,” Nature Review Clinical Oncology 10, no. 2 (2013): 108-116.

39. See O’Brien et al., supra note 13. 40. International Narcotics Control Board, Guide on Estimating

Requirements for Substances under International Control. Developed by the International Narcotics Control Board and the World Health Organization for Use by Competent National Authorities (2012), available at <https://www.incb.org/docu- ments/Narcotic-Drugs/Guidelines/estimating_requirements/ NAR_Guide_on_Estimating_EN_Ebook.pdf> (last visited April 2, 2018).

41. World Health Organization, WHO Methodology for a Global Programme on Surveillance of Antimicrobial Consumption, available at <http://www.who.int/medicines/areas/rational_ use/WHO_AMCsurveillance_1.0.pdf> (last visited April 2, 2018).

42. European Centre for Disease Prevention and Control, Euro- pean Surveillance of Antimicrobial Consumption Network (ESAC-Net), available at <https://ecdc.europa.eu/en/about- us/partnerships-and-networks/disease-and-laboratory-net- works/esac-net-about> (last visited April 2, 2018).

43. Wellcome Trust, Fleming Fund Launched to Tackle Global Problem of Drug-Resistant Infection, available at <https:// wellcome.ac.uk/press-release/fleming-fund-launched-tackle- global-problem-drug-resistant-infection> (last visited April 2, 2018).

44. J. Cleary et al., “Formulary Availability and Regulatory Bar- riers to Accessibility of Opioids for Cancer Pain in Africa: A Report from the Global Opioid Policy Initiative (GOPI),” Annals of Oncology 24, no. 11 Supp (2013): xi14-xi23; J. Cleary et al., “Formulary Availability and Regulatory Barriers to Accessibility of Opioids for Cancer Pain in Asia: A Report from the Global Opioid Policy Initiative (GOPI),” Annals of Oncology 24, no. 11 Supp (2013): xi24-xi32.

45. See Cherny et al., supra note 27. 46. The Review on Antimicrobial Resistance, Chaired by Jim

O’Neill, Antimicrobials in Agriculture and the Environment: Reducing Unnecessary Use and Waste (December 2015), available at <https://amr-review.org/sites/default/files/Anti- microbials%20in%20agriculture%20and%20the%20envi- ronment%20-%20Reducing%20unnecessary%20use%20 and%20waste.pdf> (last visited April 2, 2018).

47. See World Health Organization, supra note 35. 48. United Nations, Political Declaration of the High-Level Meet-

ing of the General Assembly on Antimicrobial Resistance (2016), available at <http://www.un.org/pga/71/wp-content/ uploads/sites/40/2016/09/DGACM_GAEAD_ESCAB-AMR- Draft-Political-Declaration-1616108E.pdf> (last visited April 2, 2018).

49. G20 Germany 2017, Berlin Declaration of the G20 Health Ministers, available at <https://www.bundesgesund- heitsministerium.de/fileadmin/Dateien/3_Downloads/G/ G20-Gesundheitsministertreffen/G20_Health_Ministers_ Declaration_engl.pdf> (last visited April 2, 2018).

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Supplementary Table 1 Identified Control Measures in the Single Convention

Measure Reference to the Single Convention

Drug classification system

Controlled substances are placed in different schedules (Schedule I-IV) according to their abuse poten- tial and are under different degrees of control. Schedule I drugs are subject to all applicable measures.

Annexed to the Single Convention, Article 2

The Commission on Narcotic Drugs (CND), based on recommendation by the WHO, may amend the drug classification list. A state may propose amendments to the lists.

Article 3 and 47

Prescribing and dispensing

A medical prescription is required for the supply or dispensation of drugs to individuals for Schedule I drugs.

Article 30

If deemed necessary, countries may require that prescriptions for Schedule I drugs are written on of- ficial forms to be issued in the form of counterfoil books by the government or authorized professional associations, and be kept for a period of not less than two years.

Article 30 and 34

Governments may choose to regulate the packaging of medicines (a clearly visible double red band on the inner package containing a drug or wrapping thereof).

Article 30

Consumption control and monitoring

Article 19

Article 12

If the annual requirements for consumption change, the government may submit supplementary esti- mates to the INCB.

Article 19

Article 20

Governments must report on seizures and stocks as of 31 December. Article 19

The INCB shall examine the statistical returns with a view to determining whether governments com- ply with the provisions of the Single Convention, and may require further information if considered necessary.

Article 13

The total quantities of each drug manufactured and imported must be within the limit of the country’s estimated requirements.

Article 21

If the quantity manufactured and imported in any one year exceeds the country’s estimated require- ments, this shall be deducted from the required estimates in the following year.

Article 21

If the quantity exported to any country exceeds the total of the estimates for that country, further ex- ports authorizations shall not be authorized to that country (except under certain circumstances).

Article 21

Records of manufacture, acquisition and disposal for each individual drug are to be kept by governmen- tal authorities, manufacturers, traders, scientific institutions and hospitals. Such records shall be pre- served for a period of not less than two years.

Article 34

Storehagen et al.

Measure Reference to the Single Convention

Licenses

All persons and enterprises involved in the manufacture, trade, distribution, import or export of drugs must be controlled under government license (except when carried out by a State enterprise).

Articles 29, 30, 31

Import and export licenses are required for each international transaction. Article 31

All persons who obtain licenses must have adequate qualifications for effective and faithful execution of laws and regulations enacted to implement the Single Convention.

Article 34

Governments shall require that the drug labels show the exact drug content by weight and percentage for Schedule I drugs (not required when dispensed to an individual on medical prescription).

Article 30

Drug control organs

The international control organs consists of a Board (the International Narcotics Control Board) and a Commission (the Commission on Narcotic Drugs). The United Nations (UN) covers the expenses, and non-UN members shall contribute based on decisions made by the UN General Assembly. The WHO has an advisory role.

Article 5, 6 and 3

The Commission on Narcotic Drugs (CND) deals with all drug-related matters. CND decides, on the basis of recommendations by the WHO, to place narcotic drugs under international control. CNC also advices the Board on any relevant matters pertaining to the control of narcotics, and supervise the implementation of the aims and provisions of the Single Convention.

Article 8

The Board (INCB) is the independent, monitoring body for the implementation of the Single Conven- tion. Its functions include to ensure adequate availability of drugs for medical and scientific purposes, prevent illicit drug activities and trafficking, and to administrate the international reporting system for estimating consumption needs and providing estimate returns. The Board also has an enforcement power towards countries failing to carry out the provisions in the Convention. This can include calling upon governments to adopt remedial measures, propose that a study is carried out, or recommend that import/export be stopped for a period. INCB can also call the attention to the Parties, the Council and the Commission and publish a report on the matter.

Article 9, 10, 12, 13, 14

Government obligations and rights

Governments must adopt necessary legislative and administrative measures to carry out the provisions of the Single Convention.

Article 4

Governments are allowed to apply stricter national control measures than those required by the Con- vention, for example apply all or some of the control measures applicable to Schedule I drugs to include Schedule II or Schedule III drugs.

Article 39

All governments may propose amendments to the Convention. Article 47

Illicit activities and abuse

Possession of drugs is not permitted, except under legal authority. Article 33

Governments shall co-ordinate actions against illicit traffic at the national level, and assist and co-oper- ate with other governments. Information relating to illicit drug activity shall be furnished to the Board and the Commission if deemed appropriate.

Article 35

Governments must adopt measures to ensure that drug activities contrary to the provisions of the Convention are punishable offences when committed intentionally.

Article 36

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Measure Reference to the Single Convention

Illicit activities and abuse

Illicit drug activities conducted by drug abusers may be subject to other measures than punishable of- fenses (e.g. treatment, rehabilitation etc.), or these may apply in addition to the punishable offenses.

Article 36, 38

Governments shall give special attention to and implement measures against the abuse of drugs, and promote training of personnel working with drug abusers, including the public if there is a risk that drug abuse will become widespread.

Article 38

Measures specific to opium, cannabis and coca leaf

If the Board finds that nationally produced opium has been introduced into the illicit traffic, the Board can decide to make deductions from the nation’s production quota.

Article 21 bis

A party shall prohibit cultivation of opium poppy, the coca bush or the cannabis plant if it considers such a measure to be necessary to protect public health and welfare and preventing the diversion of drugs into the illicit traffic.

Article 22

A party that permits cultivation of opium poppy, coca bush or cannabis plant shall establish a designated government agency to control the cultivation.

Article 23, 26 and 28

The international trade of opium, and consequently the production of it, is restricted by the Single Convention. A Party shall take into account the prevailing world need for opium before producing or increasing production of opium, and countries need to apply to certain control procedures and limit the amount that can be exported to other countries. The prohibition of trade is not applicable to those countries which during the 10 years immediately prior to 1 January 1961 exported opium.

Article 24

A phase out period allowed countries to continue the use of opioid, coca and cannabis for non-medical use for countries where such use was traditional and permitted on 1 January 1961 (15 years for opioid and 25 years for coca and cannabis).

Article 49

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