Drug and Therapeutics Committees.

Drug and Therapeutics Committees. Use of Pharmacoeconomics in Drug Reimbursement in Australia, Canada, and the United Kingdom

 

1 Drug and Therapeutics Committees

1.1 Why are drug and therapeutics committees (DTCs) needed?

1.2 Goals and objectives of the DTC

1.3 Functions of the DTC

1.4 Role of the DTC in the drug management cycle

2. Structure and organization of a drug and therapeutics committee

2.1 Principles in setting up a DTC

2.2 Steps in setting up and managing the DTC

3. Managing the formulary process

3.1 The formulary process

3.2 The formulary list (essential medicines list)

3.3 Formulary manual

3.4 Standard treatment guidelines (STGs)

3.4.1 Developing, adapting or adopting standard treatment guidelines

3.4.2 Steps in developing and implementing STGs

4.Tools to investigate the use of medicines

4.1 Stepwise approach to investigating the use of medicines

4.2 Analysis of aggregate medicine use data

5 International Experience of Pharmacoeconomics using

5.1 Introduction

5.2 Use of Pharmacoeconomics Overseas

5.2.1 Australia

5.2.2 Canada

5.2.3 United Kingdom

5.3 Comparisons in the Use of Pharmacoeconomics across The Four Countries: The Case of the Human Papillomavirus Vaccine

5.3.1 Australia

5.3.2 Canada

5.3.3 United Kingdom

5.3.4 United States

5.3.5. Examples of structured order forms from a hospital in Nepal

 

1 Drug and Therapeutics Committees

Inappropriate use of medicines wastes resources and seriously undermines the quality of patient care. A drug and therapeutics committee (DTC) can significantly improve drug use and reduce costs in hospitals and other health care facilities in the following ways:

• providing advice on all aspects of drug management

• developing drug policies

• evaluating and selecting drugs for the formulary list

• developing (or adapting) and implementing standard treatment guidelines

• assessing drug use to identify problems

• conducting interventions to improve drug use

• managing adverse drug reactions and medication errors

• informing all staff members about drug use issues, policies and decisions.

 

1.1 Why are drug and therapeutics committees (DTCs) needed?

Essential medicines are one of the most cost-effective ways of saving lives and improving health, and constitute 20-40% of health budgets in many developing countries. Increasing costs and lack of resources often result in public health systems being unable to procure sufficient medicines to meet patient demand. Despite this, medicines are often managed and used inefficiently and irrationally. This may be due to many factors, for example inadequate training of health staff, lack of continuing education and supervision, or lack of updated, reliable, unbiased drug information. Particular areas of inefficiency and drug use problems include:

• poor selection of medicines, without consideration for relative efficacy, cost-effectiveness or local availability

• inefficient procurement practices, resulting ion-availability, inadequate quality, wastage, or use of unecessarily expensive medicines

• prescribing not in accordance with standard treatment protocols

• poor dispensing practices resulting in medication errors, and patients’ lack of knowledge about dosing schedules

• patients not adhering to dosing schedules and treatment advice.

Inefficient use of medicines affects the safety and quality of therapeutic care and wastes resources. According to WHO (1985):

Rational drug use requires that the patients receive drugs appropriate to their clinical needs in doses that meet their individual requirements (right dose, right intervals and right duration). These drugs must be of acceptable quality, and available and affordable, at the lowest cost to patients and the community.

When the use of medicines is not in accordance with this definition, there are often undesirable health and/or economic outcomes. Such outcomes include insufficient therapeutic effect, adverse drug reactions, preventable side-effects and interactions from medicines, and increasing resistance of bacterial pathogens to antimicrobial medicines; these may all result in increased or prolonged hospital admissions, which are expensive.

Some inefficiencies result from lack of an effective forum that brings together pharmacists, clinicians and administrators to balance the demand for quality care with financial constraints. There may be tension between prescribers and financial managers about which medicines should be available for what problems. DTCs are a forum to bring together all stakeholders involved in decisions about drug use; they may exist at any level within the health-care system – at district level (overseeing primary health-care facilities), in hospitals, or at the national level. In developed countries hospital DTCs have been shown to be very effective in safeguarding and promoting efficient and rational use of medicines (Crawford and Santell 1994, Weekes and Brookes 1996) by, for example:

• establishing documented rules and policies for all aspects of drug management including the selection of formulary list medicines and agreement of treatment protocols

• conducting continuing education, audit and feedback, drug utilization review and monitoring of adverse drug reactions and medication errors.

 

1.2 Goals and objectives of the DTC

The goal of a DTC is to ensure that patients are provided with the best possible cost-effective and quality of care through determining what medicines will be available, at what cost, and how they will be used.

In order to achieve this goal a DTC will have the following objectives:

• to develop and implement an efficient and cost-effective formulary system which includes consistent standard treatment protocols, a formulary list and formulary manual

• to ensure that only efficacious, safe, cost-effective and good quality medicines are used

• to ensure the best possible drug safety through monitoring, evaluating and thereby preventing, as far as possible, adverse drug reactions (ADRs) and medication errors

• to develop and implement interventions to improve medicine use by prescribers, dispensers and patients; this will require the investigation and monitoring of medicine use.

 

1.3 Functions of the DTC

There are many possible functions of a DTC, and the committee must decide which to undertake as a priority; this decision may depend on local capacities and structure. Furthermore, certain functions will require liaison with other committees or teams, for example the infection control committee or the procurement team. The most important DTC functions are summarized below.

1.3.1 Advisory committee to medical staff, administration and pharmacy

The DTC is a valuable resource that can provide advice to medical staff, nurses, administration, pharmacy and other departments and groups within the hospital. The DTC can advise on all issues, policies and guidelines concerning the selection, distribution and use of medicines. Usually a DTC will provide advice and an executive body, usually the pharmacy or hospital management, will implement it.

1.3.2 Development of drug policies

The DTC is the most appropriate body to develop drug policies within a hospital or group of health facilities, since the committee members will have the most experience and training in drug therapy and supply. Policies and procedures are the primary activity within a DTC, since they provide the foundation for other recommendations that may later arise from the DTC. Drug policies may vary in different hospitals and countries, but all hospitals should have specific policies concerning:

• criteria for inclusion of medicines on the formulary list (essential medicines list (EML))

• standard treatment guidelines and treatment algorithms, which should be the basis of formulary selection

• periodic use of medicines not on the formulary list, for example restricting their use to specified prescribers on a named patient basis only, or only allowing 10% of the hospital medicines budget to be spent on them

• expensive or dangerous medicines, such as third-generation antibiotics or oncological drugs, which are restricted to certain practitioners, departments or patients (structured order forms may be used to implement this policy)

• drugs that are under investigation for safety or efficacy

• generic substitution and therapeutic interchange

• drug representatives and promotional literature.

1.3.3 Evaluating and selecting medicines for the formulary list

Perhaps the most important function of a DTC is the evaluation and selection of medicines for the essential medicines list or formulary list. Drugs should be selected on the basis of the standard treatment guidelines or protocols that have been developed or adapted for use in the hospital or health facilities. The evaluation of medicines requires significant expertise and time commitment and a rigorous, transparent approach. Documented evidence for the efficacy, safety, quality and cost of all drugs under consideration for inclusion in the formulary list must be examined. Periodic review is necessary because of changing costs and indications, new information on safety, and the emergence of new medicines. The documents reviewed will depend upon the expertise of the committee and may include reputable textbooks, published treatment guidelines and formularies, newsletters and primary drug literature. See section 3.2 and chapter 4 for more information on selection and evaluation of medicines.

1.3.4 Developing standard treatment guidelines

Standard treatment guidelines (STGs) or protocols are a proven way to promote rational use of medicines provided they are:

• developed in a participatory way involving end-users

• easy to read and up to date

• introduced with an official launch, training, supervision and wide dissemination (Grimshaw and Russell 1993, Woolf et al. 1999).

Furthermore, STGs provide a benchmark of optimum treatment in the monitoring and audit of drug use. A DTC should either develop STGs from scratch or adapt them from elsewhere for use in their own hospital. Development of STGs from scratch will result in greater local ownership and acceptance, but is difficult and will consume time and resources. Adaptation or adoption of STGs from elsewhere is much easier and quicker, but will result in less local ownership and acceptance.

1.3.5 Assessing medicine use to identify problems

Appropriate changes within the formulary list or other interventions may correct a number of problems in how medicines are used. It is important for the DTC to identify the priority problems and make appropriate recommendations. Appropriate methods to identify drug use problems include:

• aggregate drug consumption data review including ABC and VEN analysis and use of defined daily dose (DDD) methodology

• monitoring indicators of medicine use, including adherence to standard treatment guidelines

• drug use evaluation (DUE), also known as drug utilization review

• monitoring adverse drug reactions and medication errors

• antimicrobial resistance surveillance.

1.3.6 Conducting effective interventions to improve medicine use

There is no point in a DTC collecting information on drug use problems if nothing is done to correct the problems identified. The DTC is the main body within a hospital, or group of health facilities, responsible for ensuring that drug information is provided to health staff and also for conducting interventions to promote more rational drug use. Monitoring and supervision, audit and feedback, educational programmes, in-service training, use of standard treatment guidelines, provision of unbiased drug information, prescribing restrictions and automatic stop orders are some important interventions. See chapter 7 on strategies to promote the rational use of medicines.

1.3.7 Managing adverse drug reactions

Adverse drug reactions (ADRs) are serious in terms of patient harm (morbidity and mortality) and avoidable economic costs. One large meta-analysis estimated that ADRs cause 3-4% of all hospital admissions in the USA and that in 1994 the incidence of ADRs was 6.7% (2.2 million events) with 106 000 fatalities (Lazarou et al. 1998). These estimates should be viewed with caution because of the heterogeneity among studies and small biases in the sample, but the data nevertheless suggest that ADRs are a large and serious problem. Adverse drug reactions may be due to the unknown effects of new (or older) drugs, unknown drug combinations and interactions, or poor drug quality. DTCs are responsible for ensuring that patients are treated as safely as possible. Monitoring and minimizing adverse drug reactions is an essential part of this function.

1.3.8 Managing medication errors

Medication errors occur in all health-care settings, no matter how good the health-care staff are at prescribing, dispensing and administering medicines. Even if there is no error on the part of health-care staff, patients may take drugs incorrectly. Causes are numerous and include lack of knowledge, tiredness of staff, careless work attitudes, poor procedures, lack of policies, unfamiliar dosage forms and human error. DTCs can reduce such errors by monitoring, analysing, reporting errors and implementing corrective action.

1.3.9 Information dissemination and transparency

The DTC must disseminate information about its activities, decisions and recommendations to the staff who must implement the DTC’s decisions. This may seem obvious, but it is often forgotten. Inadequate dissemination of information leads to a loss of credibility. It is also very important that the DTC operates in such a way as to ensure transparency of all its decisions and to avoid conflict of interest. In particular, members should either have no relationship with pharmaceutical companies or declare it openly so that conflicts of interest can be avoided. The only acceptable contact with pharmaceutical companies is to ensure the flow of information about their drug products in a way that is as unbiased as possible.

 

1.4 Role of the DTC in the drug management cycle

The drug management cycle (Figure 1.1) illustrates the necessity for coordination of managerial and technical support with appropriate drug policies and guidelines, in order for any drug system to run smoothly (MSH 1997, part IV, section A on ‘Organization and Management’). The figure highlights the coordination between the DTC and the drug purchasing and inventory control body.

Figure 1.1 The drug management cycle

 

The DTC will often have to coordinate with those responsible for procurement and distribution of medicines. The DTC would not normally do the procurement itself: its role would normally be to ensure that the formulary system and other drug policies developed by the DTC are implemented by the procurement department. Every effort should be made to avoid the DTC degenerating into a forum only for making procurement decisions and complaining to the pharmacist about stock-outs. Furthermore, it is unwise to concentrate too much power over the pharmaceutical system in any one body, as this may lead to corrupt practices. The functions of selecting medicines, procurement, payments and inventory control are best kept separate (WHO/UNICEF/UNFPA/WB 1999).

 

2. Structure and organization of a drug and therapeutics committee

In order for a DTC to function it should have a multidisciplinary, transparent approach, technical competence and an official mandate. It is essential to define and document:

• the membership of the DTC, including the chairperson and secretary, and criteria for membership

• the goals, objectives and functions of the DTC

• how the DTC will operate and its terms of reference

• the funding sources identified

• the mandate – DTCs will not work without senior administrative support

• the relationship of the DTC with other subcommittees for specific areas of work

• a process for self-assessment and evaluation.

 

2.1 Principles in setting up a DTC

It may be easy to establish a DTC, with a list of core and additional members, all with different expertise, objectives and functions, but it may be very difficult to ensure that it functions effectively. Success will depend on having strong and visible support from the senior hospital management and abiding by the principles listed below.

2.1.1 A multidisciplinary approach sensitive to local politics

DTC activities will involve different cadres of health professional, who will have different experiences, beliefs, skills, practices, motivations and status. Often a DTC must manage conflict arising between clinicians and the pharmacy or administration concerning prescribing restrictions that result from the implementation of agreed guidelines. Such conflicts can be reduced if staff are convinced of the need for, and benefits of, change and there is strong institutional commitment with the support of people in authority. Wide representation on the DTC and documenting and disseminating decisions taken to correct problems in the use of medicines helps to convince health-care workers. Everyone who contributes should be acknowledged.

2.1.2 Transparency and commitment to good service

The success of a DTC will depend upon its being active, working regularly in a consistent direction and making sound decisions in a transparent way. This is especially important in medicine selection and procurement policies. The people involved should not be influenced by inappropriate drug advertisements, promotional activities or personal financial interests. All committee members should be required to sign a ‘declaration of interest’. Such a declaration can bind members to the working principles and ethics of the DTC, and to their roles and responsibilities to other health-care staff, the hospital management and the community.

2.1.3 Technical competency

A DTC must have the appropriate technical competence. Members will have different competencies and the DTC process of discussion and appraisal of drug use issues is a good way to educate members in areas outside their expertise. Good science and evidence (if possible) must be the basis of all DTC decisions.

2.1.4 Administrative support

Administrative support is very important, as otherwise a DTC may not be able to implement its decisions. Administrative support can provide the executive authority needed to gain the cooperation of senior medical staff. The administration can also provided the funds needed to undertake many of the DTC’s activities.

 

2.2 Steps in setting up and managing the DTC

The most effective way of gaining support is through a dynamic DTC that can formulate policy and guidelines with consensus of all parties and that is seen to be sensitive to comments.

STEP 1 Organizing the committee and selecting members

Opinions vary regarding the optimal size and composition of the committee. Smaller committees may be appropriate for smaller hospitals; larger ones may be useful in big hospitals with wider work perspectives. Fewer members may allow consensus agreements to be reached more easily. More members can provide greater expertise, reduce the workload for individual members, and increase the ease of implementation of decisions. All committees should have sufficient members to represent all stakeholders, including the major clinical departments, the administration and the pharmacy.

Members should be selected with reference to their positions and responsibilities and they should have defined terms of reference. In most hospitals, the membership includes:

• a representative clinician from each major specialty, including surgery, obstetrics and gynaecology, internal medicine, paediatrics, infectious diseases, and general practice (to represent the community)

• a clinical pharmacologist, if available

• a nurse, usually the senior infection control nurse, or sometimes the matron

• a pharmacist (usually the chief or deputy chief pharmacist), or a pharmacy technician where there is no pharmacist

• an administrator, representing the hospital administration and finance department

• a clinical microbiologist, or a laboratory technician where there is no microbiologist

• a member of the hospital records department.

Other members may also be included for their particular expertise, for example a drug information specialist, quality assurance specialist or consumer group representative. In Australia consumer representatives have included a retired judge, a psychiatric patient, a member of a pensioners’ association and a volunteer hospital worker. However, with regard to consumer representatives, “beware the politician with a hidden agenda”.

A dedicated and committed chairperson and secretary are critical to the success and efficiency of a DTC. In most hospitals, a senior medical doctor, ideally well-known and respected, is appointed as the chair and the chief pharmacist as the secretary. The chair and secretary should be allotted sufficient time for their DTC functions, and this should be included in their job descriptions and terms of reference. The allotted time should be sufficient to cover all DTC meetings and other work in relation to the meetings. Nonmember specialists can be invited during discussions of important issues. In large hospitals, various subcommittees can be established to address particular issues, for example antibiotic use, adverse drug reactions, medication errors and drug use evaluation/audit. All hospitals should have an infection control committee; if such a committee does not exist, the DTC should establish it. Where other committees exist, the DTC should liaise and coordinate with them in order to avoid duplication of activities.

STEP 2 Determine the objectives and functions of the committee

It is not possible for a DTC to do everything. The first thing a DTC should do is to agree its terms of reference, which specify the DTC’s place in the organizational structure of the hospital, its goals, objectives, scope of authority, functions and responsibilities. Once basic functions, such as a formulary system, are implemented, the DTC can move on to other activities. Sometimes the initial functions of the DTC, during the time of organization, depend on the prevailing clinical and pharmaceutical management problems that must be immediately addressed. This is a good way of getting the support of the management and the agreement of medical personnel. Figure 2.1 shows how the different possible functions of a DTC interrelate. The DTC is responsible for maintaining standards. In order to do this, the DTC must define standards, assess performance, diagnose why performance is poor and introduce measures to improve it.

Figure 2.1 The DTC’s cycle of activities and function

 

STEP 3 Determining how the committee will operate

• Regular meetings of the DTC, at least quarterly and preferably monthly, are important. The schedule may vary depending oeeds. Special meetings can be convened wheecessary. The length of meetings should be limited, as clinician members of the committee are unlikely to attend or to stay throughout if the meetings are too long.

• Regular attendance of members at committee meetings is often a problem. As a solution, some institutions make it a part of the requirements for reappointment. Other institutions provide some monetary incentives, or serve food or refreshment at meetings.

• The agenda, supplementary materials and minutes of the previous meeting should be prepared by the secretary and distributed to the members for review in sufficient time before the meeting. These documents should be kept as permanent records of the hospital and should be circulated to chairpersons/directors of all clinical departments.

• All DTC recommendations should be disseminated to the medical staff and other concerned parties and authorities in the hospital. Regular hospital activities such as grand ward rounds and clinical discussions can be used as venues to discuss recommendations and to educate the health staff on the proposed policies for implementation.

• All DTC operating guidelines, policies and decisions should be documented. This documentation should include the decisions on actions to be taken if the decisions, guidelines or policies are not followed. Relevant documentation must be made available to interested parties such as staff members and drug companies. Members of the committee should be responsible for disseminating the resolutions of the DTC.

• Liaison of the DTC with other hospital committees and regional or national committees is important, for two reasons:

– to harmonize related activities (for example, surveillance of antimicrobial resistance (AMR) and antimicrobial use)

– to share information concerning common activities (for example, monitoring of adverse drug reactions and educational strategies such as continuing medical education).

STEP 4 Seeking a mandate

Only with a mandate from the most senior authority in the hospital is a DTC credible and sustainable. The mandate of a DTC should specify:

• its roles and functions

• its place in the organizational structure

• its membership

• its scope and lines of authority.

The strongest mandate a DTC can have is that issued by the government, as in Zimbabwe. In some industrialized countries, hospitals are required to have DTCs in order to be accredited by professional societies and universities as training institutions. In other countries patients can only get reimbursement for treatment from hospitals that are accredited by the insurance companies and such accreditation may require functioning DTCs.

STEP 5 Identifying budgetary sources

The DTC must be able to identify budget resources to support its own activities (such as meetings or incentives for its members) and those activities it recommends for implementation (for example, educational programmes, development of standard treatment protocols, drug utilization review and supervision). Budgeted staff time should also be reflected in their job descriptions. Usually the budget requirement is not substantial and can be justified to the hospital administration on the basis of drug cost savings that can be realized through the DTC activities. The DTC should be able to demonstrate its own cost-effectiveness when requesting a regular budget allocation from the hospital management. To this end, the DTC should prepare an annual action plan with corresponding budget requirements. It is more convincing to present budgetary requirements together with past or potential future cost savings.

STEP 6 Forming subcommittees to address specific issues

Often there are specific areas which need a great deal of extra work and expertise that the DTC cannot provide or give time to, for example, the use of antimicrobials. Many DTCs have dealt with this issue by forming a subcommittee to work in the specified field on behalf of the DTC and report back. See chapter 8 on antimicrobials and injections.

 

BOX 2.1 INDICATORS TO ASSESS DTC PERFORMANCE AND IMPACT

• Is there a DTC document that indicates its terms of reference, including its goals, objectives, functions and membership?

• Is the DTC in the organizational chart of the hospital?

• Is a budget allotted to DTC functions?

• Does the DTC have established criteria and authority concerning drug selection?

– How many medicines are there in the hospital formulary?

– Are there documented criteria for addition to and deletion from the list and requests for the use of non-formulary medicines?

– What percentage of prescribed medicines belong to the hospital formulary?

• Has the DTC been active in the development and implementation of STGs?

– Has the hospital developed/adopted its own STGs?

– Have drug utilization studies been performed to assess adherence to STGs?

• Has the DTC organized educational activities about medicines?

– Have there been any organized training and lectures for health-care staff?

– Is there an established library accessible to staff?

– Is there continuing medical education?

– Is there a drug information service available to staff?

• Have any intervention studies to improve medicine use been undertaken?

• Has the DTC been involved in drug budget allocation?

– Was the DTC consulted during drug budget allocation?

– Was DTC clearance needed prior to drug budget approval?

• Has the DTC developed a policy for controlling the access of drug representatives and promotional literature to hospital staff?

STEP 7 Assessment of the DTC’s performance

Self-assessment and evaluation of the DTC are very important if performance and impact are to be improved. The organizational development and performance of the DTC should be monitored continuously and documented, especially if the DTC expects the hospital management to provide continuing funds. Some indicators that can be used in DTC self-assessment are shown in box 2.1. These indicators are considered to be core parameters that should be used. However, the DTC can develop other indicators and measures that will suit its purpose. Most important is for the indicators to be used in evaluating the impact of the DTC. In this way, the DTC may see if it is achieving its goals and objectives and justify the continued support of the hospital management.

 

3. Managing the formulary process

The formulary process is critical to good health care and consists of developing and implementing:

• a formulary list (essential medicines list) consisting of the most cost-effective, safe, locally available drugs of assured quality that will satisfy the health care needs of the majority of the patients

• a formulary manual containing summary information on medicines

• standard treatment guidelines containing essential information on how to manage common diseases.

A formulary list and formulary manual should be developed and maintained based on recommended treatments from standard treatment guidelines, using explicit drug selection criteria, that have been agreed previously by all departments. Standard treatment guidelines can be adopted or adapted from elsewhere, which is less work, or developed from scratch, which involves a great deal of work but may result in more acceptability and use due to a sense of ownership. Critical to future use by health workers is their involvement in the development and updating process, the quality of the content, a user-friendly format, adequate distribution and follow-up supervision.

 

3.1 The formulary process

The formulary process is the cornerstone of good pharmaceutical management and rational drug use. It consists of preparing, using and updating a formulary list (essential medicines list, EML, or essential drugs list, EDL), a formulary manual (providing information on drugs in the formulary list) and standard treatment guidelines (STGs). Choosing the most appropriate therapies and selecting the most cost-effective good-quality drugs leads to better quality of care and more efficient, equitable use of resources.

Strict adherence to a formulary list alone will not improve treatment practice if drug selection is not based on STGs (i.e. if there is no consistency between the formulary list and the STGs). Furthermore, essential medicines can also be used inappropriately if there are no guidelines for disease management. Ideally, a formulary list should be developed after the appropriate treatment guidelines for common diseases have been identified or developed. In many countries, there are already national STGs and other texts on standard treatment protocols that can be followed and used as a starting point when developing a hospital formulary list or local STGs. Once a formulary list is established, a formulary manual, containing information on all the medicines in the formulary list, can be developed. Figure 3.1 shows the relationship between STGs and EMLs and how these affect respectively the use and the availability of medicines.

Figure 3.1 How STGs and EMLs lead to better prevention and care

 

3.2 The formulary list (essential medicines list)

Essential medicines are those that satisfy the priority health care needs of the population. They are selected with due regard to disease prevalence, evidence of efficacy, safety and comparative cost-effectiveness. Essential medicines are intended to be available within the context of functioning health systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality and adequate information, and at a price the individual and the community can afford. The implementation of the concept of essential medicines is intended to be flexible and adaptable to many different situations; exactly which medicines are regarded as essential remains a national responsibility (WHO 2002a).

It is difficult to achieve efficiency in the hospital pharmaceutical system if there are too many medicines. All aspects of drug management, including procurement, storage, distribution and use, are easier if fewer items must be dealt with. Appropriate selection of drugs can achieve the following results:

• Cost containment and enhanced equity in access to essential medicines: Procuring fewer items in larger quantities results in more price competition and economies of scale with regard to quality assurance, procurement, storage and distribution. Such economies can lead to improved drug availability at lower costs, so benefiting those who are in most need.

• Improved quality of care: Patients will be treated with fewer but more cost-effective medicines for which information can be better provided and prescribers better trained. Prescribers gain more experience with fewer drugs and recognize drug interactions and adverse reactions better. Quality of care will be further improved if medicine selection is based on evidence-based treatment guidelines.

 

3.2.1 Criteria in medicine selection

Which drugs are selected depends on many factors, such as the pattern of prevalent diseases, the treatment facilities, the training and experience of available personnel, the financial resources, and genetic, demographic and environmental factors. WHO (1999) has developed the following selection criteria:

• Only those medicines should be selected for which sound and adequate data on efficacy and safety are available from clinical studies, and for which evidence of performance in general use in a variety of medical settings has been obtained.

• Each selected medicine must be available in a form in which adequate quality, including bioavailability, can be assured; its stability under the anticipated conditions of storage and use must be established.

• When two or more medicines appear to be similar in the above respects, the choice between them should be made on the basis of a careful evaluation of their relative efficacy, safety, quality, price and availability.

• In cost comparison between medicines, the cost of the total treatment, and not only the unit cost of the medicine, must be considered. Where drugs are not entirely similar, selection should be made on the basis of a cost-effectiveness analysis.

• In some cases, the choice may also be influenced by other factors, such as pharmaco-kinetic properties, or by local considerations such as the availability of facilities for storage or manufacturers.

• Most essential medicines should be formulated as single compounds. Fixed-ratio combination products are acceptable only when the dosage of each ingredient meets the requirements of a defined population and when the combination has a proven advantage over single compounds administered separately in therapeutic effect, safety or compliance.

• Drugs are specified by the international nonproprietary name (INN) or generic name without reference to brand names or specific manufacturers.

All DTCs should agree an explicit set of criteria, based upon the WHO criteria, for selecting medicines, so that the selection process can be objective and evidence-based. Without an evidence-based approach, decisions may be taken according to the doctors who ‘shout loudest’, and it may be difficult to persuade other prescribers to abide by the list. The criteria for drug selection and the procedure for proposing a drug to be added to the formulary list should be published. Not all evidence is equally strong. For example, randomized controlled trials are less subject to bias than expert opinion and are therefore thought to constitute a higher level of evidence. The level of evidence should be acknowledged when publishing selection criteria and decisions. One classification scheme for levels of evidence is that used by the Scottish Intercollegiate Guideline Network (SIGN), as shown in Table 3.1.

 

3.2.2 Developing and implementing a formulary list

The hospital formulary list should be consistent with the national essential medicines list (EML), if the latter is available. It is very important that an explicit and previously agreed process and selection criteria be followed at each step in order to increase prescriber confidence in the validity and usefulness of the list.

STEP 1 Prioritize a list of common problems/diseases being treated in the hospital and determine the first choice of treatment for each problem

The diseases may be ranked to identify the most common diseases being treated in the hospital by consulting all medical departments and reviewing the previous hospital mortality and morbidity records. For each disease, an appropriate first-choice of treatment should be identified using STGs – either nationally or locally developed. If there are no published STGs endorsed by the health ministry, publications by WHO, unbiased professional organizations and academia can be used. Alternatively, an expert committee can be brought together to identify the appropriate treatment for each of the common health problems. A commonly used alternative method of developing a formulary list – easier, but not recommended – consists of reviewing the existing formulary list of the hospital concerned or any other hospitals in the country. In such circumstances, the WHO model list of essential medicines (WHO 2002a) may also be used as a starting point. The capability of the hospital and its staff to handle specific drugs should not be forgotten during the selection process. For example, warfarin is not suitable for use unless the hospital has a facility to monitor prothrombin time (blood clotting time).

STEP 2 Draft, circulate for comment, and finalize the formulary list

A draft of the list must be prepared. It is useful to identify:

• the most important medicines (which are absolutely essential) and those that are less essential

• the most expensive medicines

• whether all the medicines that are prescribed in large volumes, or are expensive, are essential (ABC analysis and VEN analysis).

Each department, whether clinical or involved ion-clinical drug management, must be given the chance to comment on the list. The DTC must deliberate on their comments and provide feedback. All information to be discussed and deliberated upon, such as disease profile and STGs, must be available during the discussions, together with evidence-based reviews where possible. Finally, the DTC must agree and disseminate the formulary list and the reasons for its choices.

STEP 3 Develop policies and guidelines for implementation

The formulary list will never be useful unless there are documented policies and guidelines on how it should be used. These should include:

• who should use the list (prescribers and the procurement department should both abide by the list)

• how the list should be reviewed and updated

• a clear mechanism for adding and deleting medicines from the list

• how medical staff can request medicines that are not included on the list in exceptional or emergency situations (for example, certaion-formulary drugs may be prescribed by authorized senior doctors for specified less common conditions on a named patient basis).

STEP 4 Educate staff about the formulary list and monitor implementation

All the staff in the hospital must be educated about the list. A common problem is that prescribers continue to request and use medicines not on the list. This results in patients having to buy their medicines from pharmacies outside the hospital, or the procurement group buying non-formulary medicines, without the approval of the DTC. There should be a clear system of implementation, accountability and enforcement including reprimands and sanctions. End users and opinion leaders can be involved in evaluating and enforcing the implementation.

 

3.2.3 Managing a formulary list (EML): adding and deleting drugs

All applications to add medicines to the list must be made on an official application form. Individual doctors making an application must get the endorsement of their head of department. The application should include the following information:

• the pharmacological actions of the medicine and its proposed indication

• why the medicine is superior to those already on the formulary list

• evidence from the literature to support inclusion on the formulary list

• declaration of interest as to whether the applicant has received any financial support from the supplier, i.e. the manufacturing company or wholesaler.

The request should be sent to the DTC secretary who will arrange for the request to be formally evaluated by the responsible person – either him/herself, or a drug information pharmacist, or drug information centre staff.

Evaluations of applications to add new medicines to the list

These should be conducted using explicit documented criteria, preferably evidence-based, as previously agreed by the DTC and covering the following areas:

• Criteria for consideration of new treatments for conditions not amenable to existing drug therapy, or treatments representing major improvements in survival and quality of life:

– the efficacy, effectiveness and safety of the medicine, as assessed by locally available literature

– the quality of the drug (which may be considered adequate if registered by the national regulatory body) and a supply chain of acceptable quality (with regard to manufacture, storage and transport)

– whether the hospital has the necessary clinical expertise and laboratory services to use the medicine, and what role specialists should play to regulate therapy

– an estimation of the cost (and potential savings) to the hospital should the drug be introduced – this should include costs of the medicine itself, hospitalization and investigation

– availability of the drug on the market.

• Criteria for treatments representing minor improvements in therapy compared to existing listed medicines. The committee should consider all of the above and in addition:

– whether the new drug is really superior to existing ones in terms of efficacy, safety, or convenience of dosing/administration; claimed minor improvements are often proved to be unimportant

– how the total cost for a course of treatment with the new drug compares with already listed drugs.

• Criteria for treatments that are therapeutically equivalent to existing listed medicines. The committee should consider all of the above and in addition:

– whether the new drug is really therapeutically equivalent, and not inferior, to existing drugs in terms of efficacy, safety, or convenience of dosing/administration

– whether the total cost for a course of treatment with new medicine is less than with the already listed medicines.

• Criteria for use of non-formulary medicines. If the use of non-listed drugs is allowed in certain circumstances, then these drugs need not be included in the list. Such circumstances may include:

– non-response or contraindications to available medicines

– whether to continue therapy for a patient who had been stabilized on a non-listed medicine before admission to hospital and where changing to another drug is considered detrimental.

• Criteria for restricting the use of certain drugs to specified specialist prescribers only. Such circumstances may include:

– the danger of unnecessarily increasing antimicrobial resistance with inappropriate use of third- or fourth-generation antimicrobials; thus they should be limited to prescription by infectious disease or clinical microbiology specialists

– the danger of serious side-effects that could occur unnecessarily with inappropriate use, for example chemotherapeutic or cytotoxic agents; thus they should be limited to prescription by specialized physicians with knowledge of these medicines.

Written report of the drug evaluation

A written report should be compiled by the person who conducted the evaluation, and discussed at a scheduled DTC meeting. This report should contain the following information:

• the drug monograph, including pharmacology, pharmacokinetics, efficacy as compared to placebo and other medicines, clinical trial analysis, adverse drug reactions, drug interactions, cost comparison

• recommendations based on the evidence-based information

• expert opinions and recommendations from knowledgeable and respected physicians and pharmacists

• how much the new medicine would cost the hospital

• whether the new drug belongs to the national EML and whether it is reimbursable by health insurance schemes.

Discussion and voting procedures

The report should be discussed by the DTC members and a vote taken on the recommendations presented by the person who compiled the drug evaluation report. The final decision should then be disseminated to all health-care staff in the form of minutes, iewsletters and at departmental meetings.

Non-listed requests

A register of all non-listed medicine requests should be kept by the pharmacy and the name of the requesting doctor, the name and quantity of the medicine and the indication for which the medicine was requested should be recorded. When compiled at the end of the year, this information can tell the DTC about prescriber adherence to the formulary list and can also help in deciding whether or not to add drugs onto the list.

Pruning the list

If a new medicine is added to the list for reasons of improved efficacy, safety or lower price, serious consideration should be given to deleting the medicine which was previously on the formulary list for the same indication, for two reasons:

• if the ‘new’ medicine is better, why continue to have a less good ‘old’ medicine on the list?

• if no effort is made to consider deleting medicines, none will be deleted and the list will grow in size.

 

3.2.4 Maintaining a formulary

Routine review of different therapeutic categories is an important part of formulary management. An efficient formulary management process will not passively wait for applications to add new medicines to the formulary. New drugs and treatments are emerging all the time, and without evaluation the formulary may become a collection of older, less effective drugs. Therefore, the entire formulary should be reviewed every 2-3 years. This can be done by evaluating all the formulary medicines within each therapeutic class in a systematic way on a regular basis and comparing them to other new non-formulary medicines within that class. Thus, in order to efficiently maintain a formulary, a DTC should meet regularly to discuss and decide upon:

• requests for the addition of new medicines and deletion of old medicines

• systematic review of a therapeutic class of medicines

• review of programmes to identify and resolve medicine use problems.

All decisions of the DTC should be documented (minuted).

 

BOX 3.1 PRINCIPLES OF FORMULARY LIST MANAGEMENT

• Select drugs according to the needs of patients

• Select drugs of choice for the conditions identified

• Avoid duplications, both therapeutic and pharmaceutical (dosage forms)

• Use explicit selection criteria, based on proven efficacy, safety, quality and cost

• Use evidence-based information whenever possible

• Be consistent with national EMLs and STGs

• Consider requests for the addition of new drugs only when made by health-care staff, not by the pharmaceutical industry

• Require that requests for the addition of new drugs are justified using documented evidence on efficacy, relative efficacy, safety and comparative cost-effectiveness and that the person requesting any new drug declare any conflict of interest

• Carry out annual systematic reviews of all therapeutic classes to avoid duplication.

 

3.2.5 Improving adherence to a formulary

The existence of a well-maintained formulary does not mean that prescribers will adhere to it. Methods to promote formulary adherence include the following:

• reviewing and taking action on all non-formulary medicine use; action may include adding the medicine to the formulary, educating the prescriber about the non-formulary status of the medicines or banning use of the medicine within the hospital

• prohibiting the use of non-formulary drug samples in the hospital

• establishing procedures and approved drug product lists for therapeutic interchange or substitution

• providing easy access to the formulary list, with copies at each drug ordering location and in pocket manuals for staff

• involving medical staff in all formulary decisions

• advertising and promoting all formulary changes

• establishing agreed procedures for clinical trials with non-formulary medicines.

 

3.3 Formulary manual

The formulary manual is the publication that brings all the important summary information on medicines in the formulary list together in a manual. There is no set standard on how this document is arranged or what is in the manual. Normally it would contain an alphabetically and therapeutically arranged listing of all the formulary drugs, and a section on drug usage including doses, contraindications, side-effects, drug interactions and price. Ideally the manual should include a section on the medicines of choice and alternates for treating the medical conditions of the region. The DTC may be selective in what information is presented for each item, depending on what has been approved for use locally; for example, including only some but not all dosage forms, strength, indications for use, etc. A good comprehensive formulary can provide excellent drug information for health-care staff, but developing one is a very time-consuming process. If it is to be used, it will need to be pocket-sized, distributed widely (ideally to every prescriber), regularly updated, and developed in a transparent, participatory way. The WHO model formulary (WHO 2002b), which is available in electronic format, may be a good starting point for developing a formulary manual.

 

3.4 Standard treatment guidelines (STGs)

Even with an ideal formulary list, inappropriate use of formulary drugs may occur. STGs or treatment protocols are a proven, effective strategy to promote appropriate prescribing, when used in conjunction with educational strategies to promote their use (Grimshaw and Russell 1993). STGs may be defined as ‘systematically developed statements to help practitioners or prescribers make decisions about appropriate treatments for specific clinical conditions’ (MSH 1997). As a minimum, they should contain information on clinical features, diagnostic criteria, non-drug and drug treatments (first-, second-, third-line), and referral criteria. Contrary to what is often alleged, STGs do not constrain but advise prescribers, who still retain their responsibility to decide upon appropriate treatments. STGs merely define the boundaries between the accepted norms in treating a disease based on good clinical evidence, and the practice of relying purely on clinical experience. The latter provides a very limited scientific basis and is often subject unknowingly to bias and misinterpretation which may result in expensive, inefficient disease management.

STGs are very useful in:

• providing guidance to health professionals on the diagnosis and treatment of specific clinical conditions

• orienting new staff about accepted norms in treatment

• providing prescribers with justification for prescribing decisions made in accordance with STGs

• providing a reference point by which to judge the quality of prescribing

• aiding efficient estimation of drug needs and setting priorities for procuring and stocking drugs.

The problems associated with STGs include:

• a development process which is difficult, time-consuming, and requires human and financial resources

• the need to update regularly to avoid STGs becoming obsolete

• the danger of inaccurate or incomplete guidelines which provide wrong information to prescribers, so doing more harm than good.

Common pitfalls that need to be avoided include, for example,

• including treatment choices that reflect common existing practices rather than best practice according to the evidence

 

• recommending treatment choices that do not take into account existing expertise or infrastructure.

In Europe there has been a great deal of concern about the quality of STGs and as a result there is now a move to evaluate all STGs according to defined criteria, such as those of the Scottish Intercollegiate Guideline Network (SIGN 1999) or the Appraisal of Guidelines for Research and Evaluation in Europe, AGREE (Biomed 2000). Since STGs are so important with regard to monitoring and promoting more rational use of medicines, a DTC should be very concerned with developing STGs and promoting their use. Since good-quality STGs are so difficult to develop and implement, the DTC should focus on the most common, clinically important or costliest conditions treated in the hospital. Conditions where treatment is frequently suboptimal or wasteful may also be the focus of STG development.

 

3.4.1 Developing, adapting or adopting standard treatment guidelines

STGs can range from protocols covering diseases commonly seen in primary health care to those seen only in major medical centres and tertiary hospitals. An STG manual may contain a few or many clinical conditions. The DTC can develop new STGs from scratch – a very difficult and time-consuming activity, which may be appropriate for large hospitals. Alternatively, the DTC may adapt existing national or institutional STGs to form their own local version, or simply advocate the use of existing STGs published by other groups.

Adaptation or adoption of existing STGs is much easier and may be especially appropriate for small hospitals with inexperienced DTCs. Some guidelines are freely available on the web such as those from South Africa (Essential Drugs Programme South Africa 1998) and Australia (Therapeutic Guidelines Ltd 2000). Development and publication of a hospital’s own STGs, with its own book cover, may create a sense of ownership and acceptance of the guidelines. However, the DTC will need to decide whether this sense of ownership will promote the use of the STGs sufficiently to justify the extra work involved.

Whatever option is chosen, the DTC should:

• document and disseminate its choice, and the rationale for that choice, to all health workers

• ensure that any STGs developed, adapted or adopted are consistent with national STGs and the guidelines of any national disease programmes (sexually transmitted infections, HIV/AIDS, malaria, diarrhoeal disease, tuberculosis (TB) and acute respiratory infections)

• ensure that all prescribers have a copy of the chosen STG; this may mean paying for the publication of an STG manual and giving one copy to each prescriber for personal use rather than relying on prescribers buying a copy

• make provision for review and updating of any guidelines that are developed

• educate all prescribers in the use of STGs

• do follow-up and give feedback on whether prescribers are adhering to the STGs.

 

3.4.2 Steps in developing and implementing STGs

Credibility, ownership, and hence use, will be increased if the development process uses evidence-based medicine, is participatory, is documented, and all contributors are acknowledged. It is important to document the affiliations of the contributors so that prescribers can see that authors had no conflict of interest, for example business interests with a local manufacturer or wholesaler. The procedure may follow the steps listed below.

STEP 1 Identify the working group to adapt/develop the hospital STGs

The DTC may give responsibility for drafting the guideline, searching the literature and reporting back to the DTC on progress, to one or two DTC members or to a working group or subcommittee. Whoever is chosen, it is important that staff from all departments, including general practice, clinical pharmacy and pharmacology, be encouraged to comment on the draft. They should be provided access to the information upon which the DTC will base its decisions. Hospitals without sufficient clinical experts should get an external consultant group to assist in developing, adapting and updating the STGs.

STEP 2 Develop an overall plan for developing and implementing the STGs

It is not enough merely to identify a working group and experts. The DTC should agree and document who will be responsible for drafting the STGs, who will review them and who will edit them. Other things that need to be agreed include a format, a budget, and what kind of information will be used. It is useless to put a vast amount of effort into developing STGs that will not be used by prescribers or supported by hospital management (in terms of distribution or inclusion in pre- or in-service training), so a plan and budget should also be made at this stage for publication, dissemination and implementation.

STEP 3 Identify the diseases for which STGs are needed

Each department should be asked to identify the most common diseases in their specialty area, for both outpatients and inpatients. The list of diseases as identified by the different departments should be consolidated and ranked based on prevalence, severity, impact on general health of the population and the cost to the hospital of treating the condition. Some diseases, such as skin diseases, contribute substantially to the number of patients treated and the cost of drugs provided, but cause little significant morbidity or mortality. In some situations the DTC may decide not to select all the common diseases or problems but select a small number of problems or diseases:

• where there is variation in practice and inappropriate use is known to occur

• which are not covered in other published STGs

• which are expensive to treat or which are treated with drugs that are dangerous to use, for example cancers treated with cytotoxic drugs or diabetes treated with insulin.

STEP 4 Determine the appropriate treatment

This step is critical to the development of any new STGs. Experts and clinical specialists should consider the evidence concerning appropriate treatment for each disease or clinical problem and reach a consensus based as far as possible on evidence-based information sources. Consistency with national STGs is important and recommended treatments should:

• consider non-drug treatments

• use the fewest medicines necessary

• choose the most cost-effective treatments

• use approved formulary list drugs only (although the formulary list may need to be changed according to a review of the evidence)

• identify first-, second- and if necessary third-line drugs

• determine dose and duration, contraindications and side-effects for all medicines recommended

• take into account

– the existing level of prescribers (and their diagnostic skills)

– the hospital facilities and monitoring capacity

– the affordability and availability of the drug of choice in the market.

STEP 5 Determine what information should be included in the STGs

The decision on how much information to include must be weighed carefully. A small book that fits into the prescriber’s pocket will be used more readily than a large comprehensive textbook that is kept in the library. It is always important to state clinical signs and symptoms, diagnostic criteria, drugs and dosage, clearly and concisely, but other information may be omitted. Instead, the users may be referred to more comprehensive guidelines and references that should be made available in the hospital library or drug information unit/ centre. Information that may be included in hospital STGs includes the following:

• clinical condition, its natural history and diagnostic criteria, including signs and symptoms and laboratory tests

• treatment objective, for example elimination of Plasmodium parasites from a blood smear, sputum negativity in a previously sputum-positive TB patient

• non-drug treatment

• the drug of choice for the specific disease/condition

• alternative second- and third-line drugs, together with their indications

• relevant prescribing information – dose, duration, contraindications, side-effects, warnings, toxicity and drug interactions

• referral criteria

• what to tell the patient

• cost of treatments, especially if alternatives are proposed.

STEP 6 Draft the STGs for comments and pilot test

STGs generate widely varying opinions especially among prescribers, who are unlikely to use them unless they have been involved in the development process and a consensus is reached during drafting. Thus, the draft should be circulated widely and relevant comments incorporated. In order to ensure that comments are constructive, it may be helpful to ask for responses to be given in a structured way. For example, one may ask:

• what should be changed and how

• why it should be changed, providing evidence and justification.

Once the content of an STG is agreed, a draft should be pilot tested in order to ensure that the document is clear and easily understood and the information is accurate. The size, presentation of information and layout can affect how easy a document is to read and use. Piloting STGs may be done by circulating the draft to a number of prescribers and finding out if they are able to use the draft STG.

STEP 7 Implement – publish, launch, disseminate, train and supervise

Once the final draft is approved by the DTC, it can be published and distributed to staff. Distribution should be accompanied by an official launch, some initial training for staff on the STG, its importance and how to use it. Thereafter, follow-up (in-service) training, monitoring of adherence to STGs and supervision should be carried out. As with formulary manuals, use will be enhanced if the STGs come in a pocket-size format and are distributed as widely as possible, ideally to every prescriber. Use of the STGs will also be encouraged if there is consistency of medicine selection between the STGs and the formulary list.

STEP 8 Update

Treatments can change rapidly, for example with the emergence of new drugs or new patterns of antimicrobial resistance. Thus, STGs must be updated regularly by reviewing the local antimicrobial susceptibility pattern, and other sources of information from evidence-based sources (for example reputable textbooks, drug and therapeutics bulletins or respected medical journals). The various experts and clinicians within the hospital should keep abreast of the current developments in drugs and therapeutics within their own disciplines, and inform the DTC appropriately. Once the DTC has received and accepted a sufficient number of requests for treatment revisions, the STGs can be updated. Between editions of the STGs, new information can be disseminated through circulars or drug bulletins. Unless the STGs are updated regularly (every 2-3 years) using data sources that all staff agree are acceptable, the STGs will quickly lose their credibility.

 

4.Tools to investigate the use of medicines

The first step to addressing problems of irrational use of medicines is to measure the problem, analyse it and understand the causes underlying it. There are four main methods, all of which should be regularly used by DTCs.

• Aggregate data methods involve data that do not relate to individual patients and can be collected relatively easily. Methods such as ABC analysis, VEN analysis and DDD methodology are used to identify broad problem areas in drug use.

• Drug indicators studies involve collecting data at the level of the individual patient but do not usually include sufficient information to make judgements about drug appropriateness for diagnosis. Such data can be collected by non-prescribers and can be used to identify problem areas in medicine use and patient care, and evaluate interventions designed to correct the problems identified.

• Qualitative methods such as focus group discussion, in-depth interview, structured observation and structured questionnaires are useful for identifying why drug use problems occur.

• Drug use evaluation is a system of ongoing criteria-based evaluation of drug use that will help to ensure appropriate use at the individual patient level. This method involves the detailed analysis of individual patient data.

 

4.1 Stepwise approach to investigating the use of medicines

Medicines have been used irrationally for as long as they have been available; this reduces quality of care, wastes resources and may cause harm to patients. The first step to improving drug use is to investigate what kinds of problems there are and the extent to which they occur. Unless drug use is investigated, measured and documented, it is impossible to evaluate the effectiveness of interventions to promote rational use. This chapter describes a number of methods or tools to investigate drug use. It is up to the reader to choose the combination of methods most suited to the type of problem to be investigated and the type of data available.

STEP 1 General investigation to identify problem areas

Initial investigation should identify broad areas of inappropriate use of medicines. There are two main ways of doing this:

• Aggregate data methods use data that are not collected at the individual patient level; such data are often routinely available for purposes other than investigating drug use, for example stock records. Aggregate data give an overview of drug use, which is useful in managing the formulary list.

• Indicator study methods use data which are collected at the individual patient level, for example prescriptions or patient-provider interactions. Indicator study data are collected specifically to investigate medicine use, but do not include sufficient information to make individual judgements concerning the appropriateness of a drug prescription for an individual diagnosis. Such data can therefore be collected by trained personnel who are not doctors, pharmacists or nurses.

STEP 2 In-depth investigation of specific problems

Once an area of inappropriate medicine use is identified, it should be examined in depth in order to determine the size and nature of the problem and the reasons underlying the problem. Such investigation may include, for example:

• Prescription audit to see if the treatment of a specific disease is in accordance with guidelines.

• Qualitative methods to determine the causes of a drug use problem. There may be many rational reasons why people use medicines inappropriately; unless these reasons are understood it is impossible to devise an effective strategy to change behaviour.

• Drug utilization review to see if the use of a specific medicine is in accordance with previously agreed criteria.

STEP 3 Develop, implement and evaluate strategies to correct the problem

Box 8.3 describes how the use of injections was investigated in Indonesia and then a strategy developed and implemented to reduce inappropriate use.

 

4.2 Analysis of aggregate medicine use data

Aggregate data can be used to conduct ABC analysis, therapeutic category analysis, VEN analysis, and to enable the use of defined daily dose in analyses (MSH 1997, chapter 41, pp. 633-642). All these methods are very powerful tools that a DTC can and should use to manage the formulary medicines list and identify medicine use problems. Aggregate data on drug use can be obtained from many sources within the health-care system, including procurement records, warehouse drug records, pharmacy stock and dispensing records, medication error records and adverse drug reaction (ADR) records. Aggregate data sources can be used to obtain a variety of information, for example:

• Cost of drugs used – individual drugs and drug categories

– Which are the most expensive drugs?

– On which drugs is most money spent?

– What are the most expensive therapeutic categories?

– What is the percentage of the budget spent on certain drugs or drug classes?

• Quantities (in units, for example tablets) of drugs used

– Which are the most frequently and infrequently used drugs?

– Does actual drug consumption match expected consumption according to morbidity records?

– Per capita use of specific products

• Relative use of therapeutically substitutable products

• Incidence of adverse drug reactions and medication errors.

All of this data may be broken down (disaggregated) by area of the hospital – surgical wards, medical wards, casualty department, etc. Any identified problems discovered in reviewing this data should be promptly analysed by the DTC, and a strategy to remedy the problem instituted.

 

4.2.1 ABC analysis

 

Most pharmacists and managers know that only a few drug items account for the greatest drug expenditure. Often 70-80% of the budget is spent on 10-20% of the medicines. ABC analysis is the analysis of annual medicine consumption and cost in order to determine which items account for the greatest proportion of the budget. ABC analysis can:

• Reveal high usage items for which there are lower-cost alternatives on the list or available in the market. This information can be used to:

– choose more cost-effective alternative medicines

– identify opportunities for therapeutic substitution

– negotiate lower prices with suppliers.

• Measure the degree to which actual drug consumption reflects public health needs and so identify irrational drug use, through comparing drug consumption to morbidity patterns.

• Identify purchases for items not on the hospital essential medicines list i.e. the use of non-formulary medicines.

ABC analysis can be applied to drug consumption data over a one-year period or shorter. It can also be applied to a particular tender or set of tenders. A summary of the steps is shown in box 4.1.

 

BOX 4.1 SUMMARY OF STEPS OF ABC ANALYSIS

• List all the items consumed or purchased.

• For each item consumed or purchased, write down

– the unit cost of each item (using the prices for a fixed date if prices have varied over time)

– the quantity of each item consumed or purchased.

• Calculate the monetary value of consumption by multiplying the unit cost by the number of units consumed for each item. The total value of consumption is the sum of all items.

• Calculate the percentage of the total consumption value represented by each item by dividing the value of each item by the total consumption value.

• Rearrange the list by ranking the items, in descending order, by percentage value of total consumption.

• Calculate the cumulative percentage value of the total value for each item; beginning with the first (top) item, add its percentage to that of the item below it in the list.

• Categorize your items into:

– A, those few items accounting for 75-80% of total value

– B, those items which take up the next 15-20%

– C, the bulk of items which only account for the remaining 5-10% of value.

Typically, class A items constitute 10-20% of all items, with class B items constituting another 10-20% and the remaining 60-80% being in category C.

The results may be presented graphically by plotting the percentage of total cumulative value on the vertical or y axis and the number of items (accounting for this cumulative value) on the horizontal or x axis.

 

After an ABC analysis has been completed, individual drugs, particularly from category A, should be examined to identify duplication, use of non-formulary drugs and expensive drugs for which there are cheaper therapeutic equivalents. In some cases the ABC analysis may need to take into account varying price levels, brand products and medical devices, such as syringes. ABC analysis can also be used to analyse one therapeutic class, where all the medicines have equal or similar efficacy. In summary, the major advantage of ABC analysis is that it identifies those medicines on which most of the budget is spent; a major disadvantage is that it cannot provide information to compare medicines of differing efficacy.

Using a spreadsheet computer programme such as Microsoft Excel or Lotus 1-2-3 makes ABC analysis much easier.

The ABC analysis shown in table 6.1 identifies five drug/chemical entities as consuming 62% of the budget: benzyl penicillin 1 MU injection, chloroxylenol 5% solution, fortified procaine benzyl penicillin 4 MU injection, ampicillin 125 mg/5 mL powder for suspension and 100 mL chlorhexidine 5% solution. The next step would be to investigate whether these high-cost items were all needed and were being used effectively. Such investigation might involve a drug utilization review for the different antibiotics or a comparison of the efficacy and price for the different antiseptics.

 

4.2.2 Therapeutic category analysis

Building on the ABC analysis, therapeutic category analysis can:

• identify therapeutic categories that account for the highest consumption and greatest expenditures

• indicate potential inappropriate use if taken together with information on the morbidity pattern

• identify medicines that are overused or whose consumption is not accounted for by the number of cases of a particular disease, for example chloroquine and malaria

• help the DTC choose the most cost-effective drugs within a therapeutic class and to choose alternative medicines for therapeutic substitution.

The procedure is similar to ABC analysis, and the steps are shown in box 4.2. As in ABC analysis, a small number of high-cost therapeutic categories account for most of the expenditure. More detailed analysis can be performed within each high-cost category to identify the higher cost drugs and more cost-effective therapeutic alternatives.

 

BOX 4.2 THERAPEUTIC CATEGORY ANALYSIS

• Do the first three steps of ABC analysis to produce a list of all items by volume and value of consumption.

• Assign a therapeutic category to each drug using the WHO model list of essential medicines (WhO 2002a) or according to another reference manual such as the Pharmacologic-Therapeutic Classification system used by the American Hospital Formulary Service (AHFS) or the Anatomical Therapeutic Chemical (ATC) classification system adopted by WHO.

• Rearrange the list into therapeutic categories and sum the percentage value of items in each category, in order to identify the categories accounting for greatest expenditure.

 

4.2.3 Vital, essential and non-essential (VEN) analysis

 

Sometimes there are insufficient funds to buy all the desired medicines. VEN analysis is a well-known method to help set up priorities for purchasing medicines and keeping stock. Drugs are divided, according to their health impact, into vital, essential and non-essential categories. VEN analysis allows medicines of differing efficacy and usefulness to be compared, unlike ABC and therapeutic category analyses, where only drugs of similar efficacy or action can be compared.

• vital drugs (V): potentially life-saving or crucial to providing basic health services

• essential drugs (E): effective against less severe but significant forms of disease, but not absolutely vital to providing basic health care

• non-essential drugs (N): used for minor or self-limited illnesses; these may or may not be formulary items and efficacious, but they are the least important items stocked.

Many people find it relatively easy to classify medicines as ‘N’ but very difficult to distinguish between the ‘V’ and ‘E’ categories; they prefer to classify medicines as either essential or non-essential. This does not matter, provided that the system clearly defines the different categories used and these categories allow for clear prioritization amongst items. Box 4.3 shows the steps of VEN analysis, together with some sample guidelines for establishing VEN categories. Once a VEN analysis is done, a comparison should be made between the ABC and VEN analyses in order to identify whether there is relatively high expenditure on low-priority drugs. In particular, effort should be made to delete any ‘N’ drugs that are in the high cost/high consumption category A of the ABC analysis.

 

BOX 4.3 SUMMARY OF STEPS OF VEN ANALYSIS

1 Each DTC member should classify all the medicines as V, E, or N

2 The results of each member’s classification should be compiled and an overall classification agreed in the DTC

The DTC should then:

3 identify and limit therapeutic duplication

4 examine all the N items and where possible decrease the quantities purchased or eliminate them

5 reconsider proposed purchase quantities, buying V and E items before N items and ensuring that safety stocks are higher for V and E items

6 monitor drug ordering and stock levels for V and E items more closely than for N items.

 

Table 6.2 shows a real example of a VEN analysis from Malawi, where all drugs deemed non-essential were deleted from the National Essential Drugs List.

In Malawi some medicines were regarded as non-essential because more effective alternative medicines were listed as vital or essential. For example, ferrous sulfate was regarded as non-essential, whereas ferrous sulfate with folic acid was regarded as vital. Similarly, lignocaine with adrenaline was regarded as non-essential whereas lignocaine local anaesthetic alone was regarded as essential. Some drugs were regarded as non-efficacious, for example multivitamin paediatric drops and thymol mouthwash.

 

4.2.4 Defined daily dose (DDD)

Drug consumption in terms of cost, as used in ABC analysis, can help us check whether the drug budget is spent in the most effective way, and identify problem drugs to investigate further. The analysis of medicine consumption in terms of unit quantities can help to identify over- and under-use of individual medications or therapeutic groups.

The defined daily dose (DDD) methodology converts and standardizes readily available product quantity data, such as packages, tablets, injection vials, bottles, into crude estimates of clinical exposure to medicines, such as the number of daily doses. The DDD is the assumed average daily maintenance dose for the medication’s main indication. It is defined globally for each medicine by the WHO Collaborating Centre for Drug Statistics in Oslo, Norway, (http://www.whocc.no; see next tabl. for addresses and the DDDs for some medicines). The DDD is based on the average maintenance dose for adults, but it can be adjusted for paediatric medicine use.

The units in the recommended dose of a medicine may be milligrams for solid oral formulations like tablets and capsules or millilitres for liquid oral or injection formulations. Converting aggregate quantities available from pharmacy inventory records or sales statistics into DDDs roughly indicates how many potential treatment days of a medicine have been procured, distributed or consumed. The medicines can then be compared, using units such as:

• no. of DDD per 1000 inhabitants per day, for total drug consumption

• no. of DDD per 100 beds per day (100 bed-days), for hospital use.

For instance, if the calculations for amoxicillin show that there were 4 DDDs per 1000 inhabitants per day in 2002, this suggests that on any given day, for every 1000 persons, 4 adults received a daily dose of 1 g of amoxicillin. If calculations of gentamicin use are expressed as 2 DDD per 100 bed-days, this tells us that, for every 100 beds in the hospital, every day 2 patients received 240 mg of gentamicin. The assigned DDD for amoxicillin is 1 g and for gentamicin is 240 mg. These interpretations assume that the prescribed daily dose (the quantity actually prescribed to a patient) is the same as the defined daily dose, although this may not, in fact, be the case.

These DDD units can then be used to compare consumption of different medicines within the same therapeutic group, which may have similar efficacy but different dose requirements, or medicines that belong to different therapeutic groups. Medicine utilization can be compared over time for monitoring purposes and to measure the impact of DTC interventions to improve the use of medicines. Consumption in different geographic areas or hospitals may also be compared using this methodology. Cost per DDD can also be used to compare the cost of different medicines within the same therapeutic category where the medicines have no treatment duration, such as analgesics and antihypertensives.

Important points about DDDs

• The DDD is a technical unit of measurement, established by convention, based on review of the available information of the doses recommended by the manufacturer, published drug trials and expert recommendations, and medical practice in a selection of countries. What is actually prescribed to a patient can vary according to both the illness treated and local guidelines. In such situations, the prescribed daily dose (PDD) is established by reviewing a sample of prescriptions and then used to convert readily available aggregate data in the same way that the DDD is used. When what is actually prescribed differs significantly from the DDD, the reasons and implications must be understood before the findings can be interpreted correctly.

• DDDs provide a unit of measurement that is independent of price and formulation, making it possible to assess trends in consumption of medicines and to perform comparisons between population groups and health-care systems.

• DDDs have not been established for topical medicines, vaccines, general/local anesthetics, contrast media and allergen extracts.

• The DDD method should only be used in settings where reliable procurement, inventory or sales data have been recorded.

Box 6.4 shows the steps involved in calculating DDDs, together with an example.

Table 6.3 shows a detailed therapeutic category analysis of different antihypertensive medicines using DDDs and comparing:

• consumption in units (tablet/capsules)

• consumption in monetary value

• cost per DDD

• cost per course of treatment.

The data in the table show that although methyldopa has the second lowest unit price of the six oral antihypertensives, its cost per DDD and cost per monthly treatment are the highest. Assuming that monthly treatments are prescribed, the total usage quantities suggest that slightly more than half of the patients were treated with methyldopa. There is evidence establishing thiazide diuretics and beta-blockers as first-line antihypertensives, so a DTC might investigate why the usage of methyldopa is more than twice that of propranol and atenolol combined. If appropriate, a shift from using methyldopa to one of the beta-blockers would result in therapy that is consistent with the evidence base and significant cost savings.

 

5 International Experience of Pharmacoeconomics using

5.1 Introduction

Several countries around the world have been using pharmacoeconomics as part of their formal decision-making process for the pricing or reimbursement of pharmaceuticals. Australia was the first jurisdiction to adopt such a policy in 1993 and was quickly followed by New Zealand and several Canadian provinces. In addition, several European countries request economic submissions for some, or all, new medicines, including Belgium, Finland, Ireland, Norway, The Netherlands, Portugal, Sweden, and the United Kingdom. Similar policies have also been recently adopted by some Eastern European countries, plus jurisdictions in Asia (e.g., South Korea) and Latin America (e.g., Brazil).

Now that there is growing international experience with the use of pharmacoeconomics, the question arises as to whether jurisdictions that do not currently use this approach can learn from previous attempts. This is of particular interest in the United States at present, given the debate about the use of “comparative effectiveness research” and the possibility of federal government interest in this, and related, approaches. Over the last couple of years, there has been growing interest and discussion in the United States around establishing a more formalized process or system for conducting comparative-effectiveness research (CER). While definitions differ, comparative effectiveness research entails the evaluation of alternative treatment options to treat the same condition, primarily via clinical studies. Based on these discussions, various proposals have been put forward around the call for a centralized comparative research entity, each with different configurations regarding its governance, remit, methods, and role in decision-making. While none of the proposals has yet to be adopted on the congressional level, with continued debate over the nuances of a CER entity, a wide range of stakeholders (e.g., U.S. government, business, insurers, providers, consumers, and coalitions) support such initiatives and it appears highly likely that some CER organizational form will be introduced in the United States.

Until a new CER entity is introduced, the use of pharmacoeconomics in the United States is largely decentralized, with several jointly operating health technology assessment (HTA) entities. For example, the Effective Health Care (EHC) program at the Agency for Healthcare Research and Quality (AHRQ) includes a collection of research centers that review existing evidence or generate new evidence and analytic tools. Additionally, the Centers for Medicare and Medicaid Services (CMS) has the Medicare Coverage Advisory Committee (MCAC); each of the 50 state Medicaid programs has some form of HTA procedure for drugs (the state of Washington recently extended its HTA program to also cover devices, diagnostics, and procedures); and 13 states participate in the Drug Effectiveness Review Project (DERP). Many private health plans and pharmacy benefit managers (PBMs) also operate HTA programs, and pharmacoeconomic analyses are frequently conducted by manufacturers, consulting firms, and academic departments.

The focus of this chapter is to review experience overseas and to assess whether any lessons can be learned from international use of pharmacoeconomics. The discussion will concentrate on experience in Australia, Canada, and the United Kingdom, as these are the three countries with the most extensive use of pharmacoeconomics to date. The introduction of the human papilloma virus (HPV) vaccine in Australia, Canada, the United Kingdom, and the United States will then be explored to highlight the different approaches to pharmacoeconomics in these countries. Finally, the focus will be on potential implications for the United States, given the current policy debate, drawing on the strengths and weaknesses of other jurisdictions.

 

5.2 Use of Pharmacoeconomics Overseas

5.2.1 Australia

Since 1993, pharmacoeconomic studies have formed part of submissions made  by manufacturers to the Pharmaceutical Benefits Advisory Committee (PBAC). The PBAC makes recommendations to government ministers on the listing of drugs on the Pharmaceutical Benefits Schedule (PBS). This is the list of drugs given outside of public hospitals that receive a public subsidy. Therefore, PBS listing is usually essential if a new drug is to secure a substantial market share.

Manufacturers’ submissions have to be produced in accordance with a set of guidelines set forth by the PBAC (Commonwealth of Australia 2007) and are then assessed by an independent review group. The activities are also supported by an economics subcommittee of the PBAC that contains several well-known Australian health economists. Based on the evidence and subsequent discussion, the PBAC will recommend that the drug be listed, either at the price proposed by the manufacturer or at a lower price. The committee can also reject or defer applications. The final price of the drug, if listed, is agreed upon by another government committee, after a consideration of several other factors (e.g., overseas prices, expected expenditure).

Australia has the greatest experience in the use of pharmacoeconomics and much has been written about the PBAC. One of the most interesting papers is that by George et al. (2001), who reviewed the outcome of several submissions to the PBAC and discussed why particular drugs had been approved or rejected by the committee. They found that the PBAC was unlikely to list a drug if the incremental cost per life-year gained exceeded 76,000 Australian dollars and unlikely to reject a drug for which the additional cost per life-year gained was less than 42,000 Australian dollars. However, the cost-effectiveness ratio was not the only factor determining the reimbursement decision. Other factors included the scientific rigor and relevance of the evidence for comparative safety, efficacy, and cost-effectiveness of the drug; the lack, or inadequacy, of alternative treatments currently available; the perceived need in the community; whether the drug is likely to be used only in a hospital setting; and the seriousness of the health condition for which the drug was indicated.

 

5.2.2 Canada

The use of pharmacoeconomics in Canada began at the provincial level, most notably in Ontario and British Columbia (Ontario Ministry of Health 2004; Anis et al. 1998). However, in 2002 the Common Drug Review (CDR) was established, involving all provinces with the exception of Quebec.

The CDR is administered by the Canadian Agency for Drugs and Technologies in Health (CADTH). CADTH, formerly the Canadian Coordinating Office for Health Technology Assessment, or CCOHTA, is the central agency for the coordination of HTA activities in Canada. In addition to administering the CDR, CADTH undertakes some of its own HTAs of drugs and other health technologies. It also developed the Canadian Guidelines for Economic Evaluation (CADTH 2006), which lay out key methodological standards and serve as the template for submissions to the CDR.

The CDR was established in the hope of securing standardized access to new drugs across the whole of Canada. However, its recommendations still need to be adopted by individual provinces because the provision of health care is a provincial, rather than federal, responsibility in Canada. Some provinces still retain their own drug review committees and may occasionally come to a different view from that of the CDR. In addition, there are other activities involving the use of pharmacoeconomics, such as the Joint Oncology Drug Review, which seeks to establish guidelines for the use of cancer drugs both within, and outside, hospitals.

The main challenges facing the CDR have been set out in a recent paper by Laupacis (2006), who was the founding chair of its expert committee (CEDAC). These challenges include the variable quality of manufacturer submissions and the problems of dealing with drugs for rare diseases, which are often expensive and for which the clinical evidence is often sparse.

 

5.2.3 United Kingdom

Activities in HTA in the U.K. are coordinated by the National Coordinating Centre for Health Technology Assessment (NCCHTA). The NCCHTA manages the National Health Service (NHS) research program in HTA and also administers contracts for the National Institute for Health and Clinical Excellence (NICE).

Established in 1999, NICE is the most well-known HTA entity in the U.K. It issues guidance on the use of health technologies and healthcare interventions to the NHS in England and Wales. It has four major programs of work, in investigational procedures, technology appraisal, clinical guidelines, and the evaluation of public health interventions.

The work program on technology appraisal has attracted the most discussion and debate owing to several high-profile decisions to recommend against the use of some technologies, especially expensive new cancer drugs. NICE does not control the reimbursement or pricing of drugs; the latter is a matter for the manufacturer. However, a negative recommendation from NICE usually results in highly restricted use of a given product.

As in Australia and Canada, NICE’s technology appraisal process involves a submission from the manufacturer, undertaken in accordance with the institute’s methodological guidelines (NICE 2008). The manufacturer’s submission is then assessed by an independent review group, which may provide just a critique or may undertake its own study, depending on the precise nature and complexity of the appraisal being conducted. NICE distinguishes between single technology appraisals, which are simpler and consider only one drug, and multiple technology appraisals, which are longer, more complex, and typically consider three or more drugs for treating the same condition.

The role of pharmacoeconomics in NICE’s technology appraisals is quite extensive and assessments will normally include a full decision-analytic model. It is also clear that cost-effectiveness considerations are an important part of the decisionmaking process, although NICE’s Technology Appraisal Committee does consider evidence from clinical experts and patient organizations as well as the independent assessment report.

Unlike the HTA and reimbursement agencies in Australia and Canada, NICE does not currently consider every new drug for use outside hospitals. Its agenda is set by the Department of Health and tends to focus oew technologies (the majority of which are drugs) that are likely to have a major clinical or economic impact on the NHS.

In addition to NICE, the Scottish Medicines Consortium (SMC) issues guidance on the use of all new drugs for the Scottish NHS (Cairns 2006). Its mode of operation is very similar to that of the PBAC and CDR. Also, the All Wales Medicine Strategy Group issues guidance on the use of drugs to the Welsh NHS, particularly in cases where there is no NICE guidance.

Because there is considerable information in the public domain about NICE and its activities, it is probably the most widely studied HTA or reimbursement agency. In particular, the recent report of a Parliamentary Health Select Committee (2008) discusses the strengths and weaknesses of NICE and makes several recommendations for improvement. Principally, these relate to increasing the coverage of NICE guidance (to include a higher proportion of new drugs and other health technologies) and to reducing the time taken to issue guidance.

In addition, a recent report commissioned by the National Pharmaceutical Council examines the workings of NICE in detail and discusses its relevance to the United States (Sorenson et al. 2008). For further information, see Table 13.1.

 

 

5.3 Comparisons in the Use of Pharmacoeconomics across The Four Countries: The Case of the Human Papillomavirus Vaccine

The case study being used in this chapter is the HPV vaccine. It is, however, important to note that vaccines differ from pharmaceuticals in several ways. While vaccines have many similarities to pharmaceuticals in general, they also raise additional analytic challenges, such as the need to model disease transmission. In most jurisdictions, the reimbursement of vaccines is handled by a separate decision-making structure, and it is common for payers to place a contract for supply in countries with a single payer (e.g., government). Nevertheless, pharmacoeconomic assessments, along the lines of those discussed above, are frequently made and these often have an impact on decision making.

 

5.3.1 Australia

The Australian government has invested heavily in the prevention of cervical cancer, supporting one of the most successful national cervical screening programs in the world. The program has played a central role in the approval and use of vaccines to protect against HPV.

In mid-2006, Gardasil®, the first HPV vaccine approved for use in Australia, underwent consideration by the PBAC to attain public funding (Pharmaceutical Benefits Advisory Committee 2006). The manufacturer’s submission indicated current management involving screening for cervical cancer via the national screening program as the main comparator, and presented six randomized trials comparing Gardasil and placebo. Based on the efficacy analysis, Gardasil was deemed significantly more effective than standard treatment (screening), but with similar or greater toxicity. Several economic models were provided to estimate relevant costs and outcomes over the long term. Incremental cost-effectiveness ratios ranged from $16,000 to $70,000, depending upon the cohort. The total cost of the vaccine program in the first 4 years of operation was estimated to be more than $100 million. Based on the available evidence, the PBAC rejected the application for Gardasil, given unacceptable and uncertain cost-effectiveness at the price requested. Other considerations central to PBAC’s decision included the fact that the magnitude of the per patient clinical benefit was considered small across the vaccinated population; the lack of estimation of potential costs associated with implementation; and, the significant total cost of an HPV vaccination program. Subsequent to PBAC’s decision, the Minister of Health requested that it consider a minor resubmission addressing the main issues of concern identified by the initial review. The resubmission provided a reduced vaccine price, further evidence to support the original cost-utility analysis, and the potential for a risk-sharing agreement and additional surveillance between the sponsor and the Australian government. The PBAC considered these modifications sufficient to subsidize Gardasil for use in 12–26-year-old females enrolled in school- and community-based programs under the auspices of the National Immunization Programme (NIP). Consequently, the commonwealth government funds the purchase of the vaccine, while the state and territory governments manage the immunization program, administering the vaccine in schools and local communities.

About a year later, another HPV vaccine, Cervarix®, was reviewed by the PBAC, with Gardasil as the comparator. Submission presented an indirect comparison based on three randomized trials of Cervarix versus placebo and three randomized trials of Gardasil versus placebo. A formal direct comparison was not provided, only the results from the two sets of trials. The submission presented Cervarix as equivalent to Gardasil in terms of both comparative efficacy and safety and, based on a costminimization analysis, proposed that Cervarix be included on the NIP for the same treatment population and at the same price as Gardasil. However, due to uncertainty regarding the assumptions and data inputs used, the PBAC did not accept the sponsor’s claim of cost-minimization and was therefore unable to determine a cost-effective price for Cervarix. Moreover, while Cervarix does not offer protection against genital warts (a broader benefit of Gardasil), the submission did not provide a full economic evaluation of the impact of the health forgone when Cervarix is used in place of Gardasil. Based on these considerations, PBAC rejected the submission on the grounds of uncertain cost-effectiveness.

 

5.3.2 Canada

In 2008, the Canadian Immunization Committee (CIC) published its recommendations on HPV vaccines, which are used by federal, provincial, and territorial jurisdictions to develop and implant their immunization programs (Canadian Immunization Committee 2008). A multidisciplinary, joint National Advisory Committee on Immunization (NACI)-CIC HPV Vaccine Expert Working Group, comprising a wide range of experts and key stakeholders, was established about a year prior to develop comprehensive recommendations for HPV vaccine programs. In developing its recommendations, the group examined the existing clinical data on the efficacy of Gardasil and Cervarix, as well as international and Canadian cost-effectiveness studies to determine the relative long-term epidemiologic and economic consequences of HPV vaccines. Cost-effectiveness estimates for HPV vaccination ranged from $15,000 to $37,000 in both international and Canadian studies, depending on the model used, the duration of vaccine protection, the age at vaccination, and other assumptions (e.g., use in both males and females vs. females only). The working group also considered evidence on the acceptability of HPV immunization, feasibility of eventual HPV immunization, ability to evaluate the impact of such programs, and equity and ethical concerns. Based on the aforementioned evidence, the working group recommended the use of Gardasil (Cervarix is not licensed for use in Canada), specifically for females aged 9 to 26 years. Recommended only for females aged 14 to 26 years (even if already sexually active) if they have had previous Pap smear abnormalities or a previous HPV infection. Moreover, in order to achieve higher coverage at lower cost, vaccinations should be administered prior to the onset of sexual activity and in primary school. As immunizing all Canadian females aged 9 to 26 years upon initial implementation of the program was unfeasible, it was recommended that school-based HPV vaccination of one female cohort be implemented in all Canadian provinces and territories, so that 80% to 90% of school-aged girls in select grades were immunized within 2 to 5 years. Given that the level of benefit (in both health and economic terms) associated with HPV vaccines was greatly influenced by the duration of vaccine protection, the recommendations also called for evaluation procedures to be put in place to measure the persistence of effectiveness and develop strategies for reaching vaccinated females for additional doses, if required.

Following the CIC-NACI recommendations, the government provided $300 million to the provinces and territories through a third-party fund to launch HPV vaccine programs, specifically through supporting the purchase of HPV vaccines. Similar to Australia, the provinces and territories are responsible for the delivery of the immunization program(s) and are granted flexibility in decisions about their implementation.

 

5.3.3 United Kingdom

In the U.K., the Joint Committee on Vaccination and Immunization (JCVI) serves as the statutory expert on vaccine use. It provides advice to the secretaries of state for health for England, Scotland, Wales, and Northern Ireland on matters related to the immunization of communicable diseases. In 2006, the JCVI was commissioned by the Department of Health to systematically review the available evidence on the use of HPV vaccines and their potential benefit (Joint Committee on Vaccination and Immunization 2008). The committee examined both published and unpublished evidence sources, including efficacy and burden of disease studies, cost-effectiveness analyses, feasibility studies on implementing an HPV program, and research on HPV vaccination. Much of the efficacy evidence considered by the JCVI was submitted by the manufacturers of Gardasil and Cervarix, and included clinical trial data and post-marketing surveillance reports. In their review, the JCVI concluded that both vaccines are highly effective (especially in 10- to 14-year-olds), with good safety profiles, and offer an expected immunity of about 10 years. Again, only Gardasil demonstrated effective protection against genital warts. Upon initial review of existing burden of disease and economic modeling studies, the JCVI concluded that the available evidence was not sufficient to make a recommendation, especially as the models were not U.K. specific. Consequently, the JCVI considered two particular studies commissioned to two local institutions. The cost-effectiveness analyses used followed NICE guidelines and underwent a robust review process.

Following the review, the committee recommended to the secretary of state that routine HPV vaccination of females aged 12 to 13 years would be the most costeffective, assuming the average duration of vaccine protection is at least 10 years. In addition, it would be feasible to include a time-limited “catch up” vaccination for girls aged 13 to 17 years. Vaccination of females above this age was not cost-effective given the assumed cost of vaccine and administration, and the increase in prevalence of previous infection in this age group. The JCVI recommended that the vaccine be delivered through schools, except for certain groups that may be difficult to reach (e.g., home-schooled females), in which case GPs should assume a role in delivery of the vaccine. It was considered whether Gardasil or Cervarix should be recommended for use over the other, with the committee concluding that the choice of vaccine to be purchased should be determined primarily by cost-effectiveness and, in relation, the negotiated cost of the vaccines. If offered at the same price, Gardasil was recommended due to its protection against genital warts. As with Canada, the JCVI recommended that a comprehensive monitoring and evaluation program be fully funded and implemented as an integral part of the vaccine program. The vaccination program is currently being implemented throughout the U.K. based principally on the JCVI recommendations. However, Cervarix is the sole vaccine being used in the program, following a U.K.-wide competitive procurement bid for supply of the HPV vaccine to the NHS.

                        

5.3.4 United States

In 2006, the Food and Drug Administration (FDA) approved the use of Gardasil in females 9 to 26 years of age, based on a review of the vaccine’s safety and effectiveness. Cervarix is still under FDA review and is unlikely to be on the market until 2009, at the earliest. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) subsequently recommended that girls ages 11 and 12 receive the vaccine (in three separate doses),[ This recommendation was based on several considerations, including age of sexual debut in the United States, cost-effectiveness, and the established young adolescent health care visit at ages 11–12 when other vaccines are also recommended (Javitt et al., 2008).] with a temporary “catchup” vaccination provided to women between 13 and 26 years of age who have not yet been vaccinated or completed the full vaccine series. The recommendation was based predominantly on efficacy and safety evidence, although available cost-effectiveness estimates were considered, albeit not formally. As intimated in the introduction, cost-effectiveness analysis has not assumed a formal role in coverage decision or practice guidelines in the United States, unlike the other countries highlighted in this chapter. For example, the government run vaccine fund for uninsured children (Vaccines for Children program) does not use cost-effectiveness to develop its recommendations and policies. Thereafter, the CDC advised that Gardasil be added to the routine vaccination schedule for children and adolescents. Many states also introduced legislation to require girls to be vaccinated before entering the relevant grade in school. The United States has a robust state-based infrastructure for mandatory vaccination, which became a condition of school entry in the 19th century. While an “opt-out” policy generally accompanied most of these bills, such proposals generated considerable public debate and most were not passed. In another highly contested move, the U.S. Citizenship and Immigration Service (USCIS) recently agreed to mandate Gardasil for every ageappropriate female seeking to become a legal resident of the United States.

The CDC’s guidelines arguably influenced insurance coverage of Gardasil, with many private health plans providing coverage for the vaccine. However, the extent and rates of coverage vary at both the plan and individual level. Indeed, one of the main concerns in a more fragmented system such as that of the United States is that vaccine coverage may not be at the desired or appropriate level. To narrow existing gaps in coverage, the Vaccines for Children (VFC) program added Gardasil onto its roster of vaccines provided at no or low cost to uninsured children aged 18 and younger. All of the state immunization projects have also adopted Gardasil, which provides the vaccine at $30 versus $360 (full cost) for the complete series of three injections. In addition, Merck has a patient assistance program to provide the vaccine to those 19 years and older who are uninsured and unable to afford the vaccine.

Despite such efforts and significant support for its use by a variety of stakeholders, a recent study conducted by the CDC found that while nearly 2.5 million of the country’s 10 million girls had received at least one dose of the vaccine, only a quarter of that group had received all three recommended doses (CDC, 2008). Estimates were derived from the CDC’s annual National Immunization Survey for Teens, where nearly 3,000 teens were interviewed by telephone and their answers confirmed by vaccination records from physicians. The low rate of completed vaccination with Gardasil has raised several concerns about its use, although investigators have noted that the vaccination series takes 6 months and thus not many of the participants studied would have had time to complete the full schedule (Drug Information Association, 2008). Moreover, the survey covered only girls between the ages of 13 and 17 years. Other contributing factors to the low vaccination rate may include limited public understanding that HPV causes cancer, difficulty in encouraging young women to visit the doctor, and the high cost of the vaccine, if not covered in some manner. Moreover, there has been some skepticism among parents and experts about use of the vaccine, particularly in the youngest girls (e.g., 9- and 10-year-olds), for a variety of social, economic, ethical, and health reasons. Such sentiments have generally been accompanied by requests for more parental control over HPV vaccination and additional studies to evaluate the longterm effectiveness, especially in terms of the duration of vaccine immunity, and safety of Gardasil.

It has also been recognized that additional evidence on the cost-effectiveness of HPV vaccines is needed to support appropriate guidelines for their use in the United States. A recent study by Kim et al. (2008) at Harvard University found that Gardasil is cost-effective in pre-adolescent girls aged 11 and 12 years at $43,600 per QALY, an estimate that falls below the $50,000–$100,000 per QALY threshold often used in the United States to ascertain maximum cost-effectiveness. However, this result assumes lifelong immunity, which has not yet been demonstrated in clinical studies. Cost-effectiveness declines significantly among older females (19 to 26 years old), with vaccination for girls and women up to age 26 estimated at $152,700. The results of this study, coupled with the recent CDC report, have been used to highlight the need for further evidence on the long-term costs and benefits of Gardasil, especially before mandates for vaccination are put into place.

This brief discussion of the experience with the use of pharmacoeconomics in three countries illustrates that there is much to be learned from other jurisdictions. Although the precise models from elsewhere cannot simply be transported to another country, it is clear that some approaches work better than others and that elements of good practice can be specified. The debate about the extended use of pharmacoeconomics is currently taking place in many jurisdictions, including the U.S. Of course, as this debate progresses, it will become clearer as to which aspects of overseas experience are most relevant to the direction that is eventually taken. However, despite the eventual outcome of the current debate about the use of pharmacoeconomics in the U.S. and other countries, the experience of other jurisdictions that have already implemented these policies contains several messages that have general relevance. Those in charge of the implementation of pharmacoeconomics iew settings should try to make good use of this accumulated experience.