Pharmaceuticals And Productivity: Investing In Human Capital

Health benefits — Are employers getting the most for their money?

Role of pharmaceuticals — How drugs produce substantial savings in both direct and indirect costs for the most common chronic illnesses seen in the workplace

New medications — Incremental pharmaceutical improvements substantially improve workplace productivity

Pharmaceuticals and Productivity: An Investment in Human Capital

Keeping workers healthy and active — Today’s drugs help reduce absenteeism and improve job performance

Pharmaceuticals and disease management strategies — Pharmaceutical intervention and drug-based treatment protocols can reduce health care costs and improve clinical outcomes

N AT I O N A L P H A R M AC E U T I C A L CO U N C I L

2

0

0

1

TAB LE O F CO NTE NTS Overview...........................................................................................................................1 What Are We Getting for Our Money? ...................................................................1 New Pharmaceuticals Save Both Direct and Indirect Costs............................3 Incremental Benefits of New Medications............................................................4 New Pharmaceuticals Reduce Treatment Costs and Improve Workplace Productivity ......................................................................5 Disease Burden and Benefits of Drugs for 10 Diseases Prevalent in the Workplace................................................................6 Allergic Rhinitis ...............................................................................................8 Arthritis...............................................................................................................9 Asthma.............................................................................................................10 Diabetes ..........................................................................................................10 Depression ......................................................................................................11 Heart Failure ..................................................................................................13 Hypertension..................................................................................................14 Coronary Heart Disease (CHD)................................................................15 Migraine ..........................................................................................................16 Gastrointestinal Disorders .........................................................................17 Cost Savings Through Disease Management and Practice Guidelines .....................................................................................................19 Conclusions ...................................................................................................................21 References .....................................................................................................................22

OVE R VI E W

What Are We Getting for Our Money?

New therapies have the potential to produce economic savings and benefits both outside of the health care system (indirect savings) and within the system (direct savings). This report explores the question of whether spending on pharmaceuticals has a positive payoff. In short, do we get a good return on our investment? The conclusions are as follows:

Although still focused on cost management, employers are increasingly asking for hard information on the return they are getting from their health care expenditures, including those for pharmaceuticals.

d

Increases in drug expenditures have been offset by substantial improvements in health and by direct savings associated with reductions in the cost of illness. The benefits of new drugs include increased longevity and quality of life, and less use of hospitals, emergency rooms, nursing homes, and other expensive services.

d

New medications reduce the indirect costs of illness, especially by improving workplace productivity. This can be especially important for employers because productivity can be severely compromised by illness. Modern drugs for major illnesses of employed persons have been shown to reduce absenteeism and to improve performance on the job.

d

Disease management programs for asthma, congestive heart failure, and diabetes that use pharmaceutical intervention as a critical part of their overall strategies have repeatedly demonstrated effectiveness in reducing health care costs and improving patient quality of life.

d

Control of spiraling health care costs is a high priority for employers today, and pharmaceutical expenditures are a prime cost-cutting target because they are rising faster than many other health care costs. A recent study addressed the question of what factors are driving the recent increase in drug expenditures. Using large national claims databases covering managed care plan enrollees and employees covered by large employer-provided health plans, researchers examined information on drug therapies for seven common medical conditions (allergy, asthma, depression, diabetes, gastrointestinal problems, high cholesterol, and hormone replacement). It was found that for each condition, increased prescription volume, not rising prices, accounted for higher levels of spending.1 This increased volume growth resulted from more patients, more prescriptions per patient, and more days of therapy. The main factors accounting for rising drug costs in recent years include the following2,3:

Expenditures on medications by employers are best viewed as an investment in improved health and productivity of the workforce.

| 1 |

d

General inflation in all sectors of the economy, including pharmaceuticals.

d

Many new drugs available to patients today are more effective than older drugs, such as proton pump inhibitors, which have replaced H2-receptor antagonists, and non-sedating antihistamines, which have replaced older sedating therapies.

d

New therapies for previously untreatable conditions, such as acquired immunodeficiency syndrome, are now available.

d

Patients are becoming more educated about their health and are increasing demand for certain brand name drugs as a result of an increase in direct-to-consumer marketing.

d

to control rising costs do not consider the full value of many pharmaceutical treatments and may ultimately cost employers more. The potential impact of such programs on health outcomes and employee productivity usually is not assessed before such restrictions are imposed. Drugs have helped increase the life expectancy of Americans from 54 years in 1920 to more than 75 years today.4 In addition, medications have reduced the overall cost of disease, because they often replace more expensive surgeries and medical treatments.

New drugs for treating heart disease, cancer, and mental disorders are now replacing more traditional medical treatments that involve hospitalizations, surgery or other invasive procedures.

Many drugs save lives, and some are more cost-effective than other nondrug life-saving interventions. Figure 1 shows the costs of some drugs compared with the costs of other important health and safety interventions in saving one year of human life.

In response to rising drug expenditures, some employers and managed care organizations have introduced cost-containment programs that involve higher cost-sharing provisions for drug benefits, multitier coinsurance arrangements that favor generics and older therapies, and restricted access to certain drugs through predetermined formularies. But these blanket responses designed

In addition to their ability to save lives, pharmaceuticals may improve an employee’s health and

Figure 1 Comparable Value of Pharmaceuticals: Relative Costs to Save One Year of Life

$210,000

Home Smoke Detectors

$110,000

Annual Mammography Age 55-64

$42,000

Driver Airbag/Lap Belt

$26,000

Drug Therapy for AIDS Statin Cholesterol Drugs for Men 55-64 with Heart Disease

$20,000

Beta Blockers for Heart Attack Survivors $850

$0

$50,000

$100,000

$150,000

$200,000

$250,000

Source: Tengs et al, Risk Analysis, Vol. 15, No. 3,1995

| 2 |

costs? Dubois and colleagues1 posed the question: "If patients, for example, with milder and non-suicidal depression feel better on medication, or if more expensive but less sedating antihistamines improve concentration, are these gains worth the extra costs?" Often, the extra expenditures for newer medications result in savings in other areas, making the expenditures worthwhile.

well-being, and their cost may be offset by reduced hospital, emergency room, laboratory, or physician services, as observed for asthma. For example, Figure 2 shows the correlation between the recent increase in the use of asthma drugs and the decrease in the use of medical services.

Figure 2 Asthma-related Hospital and ER Use Decreased as Asthma Drug Use Increased

New Pharmaceuticals Save Both Direct and Indirect Costs The higher costs associated with new pharmaceuticals often are offset by reductions in other direct costs (e.g., hospitalization) and by reductions in indirect costs (e.g., improved worker productivity).

450 400

Rate per 1,000 Asthmatics

350

424

1995 1998

393

300 250

Benefits of New Pharmaceuticals

200 150 d

Reduced hospitalization

d

Improved side effect profiles

d

Reduced patient visits

d

Expanded formulary choices

d

Reduced worksite injuries

d

Enhanced patient adherence

Savvy health care purchasers need to ask the following questions when faced with increases in drug costs:

d

Reduced absenteeism

d

Enhanced longevity

d

Reduced expensive treatments

Is the added expense of a drug worth it in terms of the drug’s ability to improve health and reduce overall spending?

d

Enhanced quality of life

d

Reduced invasive treatments

d

Enhanced workplace performance

163

100 50 0

ER

($450 each)

128

Hospitalizations ($11,037 each)

Source: Protocare Sciences

d

d

Does the drug enhance or hamper employee productivity?

d

Do the answers to these questions differ for newer, higher priced drugs compared with older agents?

The reverse is also true. Research shows that cutbacks in drug spending can raise utilization in other parts of the health care budget—notably, hospital admissions, emergency mental health facilities and nursing home admissions.5,6,7,8 Some managed care plans have begun to move away from restrictive formularies and are implementing

The core question for employers is: Compared with drug or nondrug alternatives, are the benefits of newer, more expensive drugs worth their added

| 3 |

pharmaceutical management programs that are based on an integrated approach to health care. HealthNet, in California, has reported cost savings and quality improvement by investing in new drugs that are often more expensive than older agents.9 Formularies are increasingly being evaluated for their impact on overall disease management and not just drug budget costs.10 This evaluation is welcomed by most employers.

Employees Perceptions About Medications A 2001 survey of employees by Harris Interactive11 revealed the following perceptions about the value of medications: d

Seventy-nine percent of survey respondents said prescription medications enhanced productivity at work for them or someone they care about.

d

Eighty percent said that medications have helped them or someone they care about return to work more quickly after an illness.

d

Eighty percent said that medications have helped to keep them or someone they care about alive.

d

Eighty-seven percent credit prescription medications with keeping an ailment in check.

d

Ninety-three percent of respondents with private prescription drug coverage believe that prescription drugs are an "essential part" of their health coverage.

Incremental Benefits of New Medications The need for multiple agents that are similar to existing medications is often questioned. It is assumed that drugs with similar pharmacological actions are essentially identical. This is a misconception. The process of incremental innovation produces a diverse class of drugs, enabling physicians to tailor drug therapy to individual patients. New agents resulting from this process can offer advantages in the form of improved effectiveness, fewer side effects, better patient satisfaction and compliance, and greater cost-effectiveness. These gradual improvements do not necessarily increase the cost of pharmaceuticals, because the new drugs must compete with their predecessors for market share. Analysis of drug pricing indicates that most new drugs are launched at discounts relative to existing drugs in the same class.12 Thus, the more recently introduced cholesterol medications are more cost-effective than earlier ones in elderly patients,13,14 though not in lower-risk patients.15 Because they often have fewer side effects and are easier to take, newer medications can facilitate adherence to treatment regimens. Patients who do not take their medications as directed may fail to improve, worsen, or relapse. Each of these negative outcomes has an economic effect on the entire health care system. The costs of hospitalization and physician visits caused by relapse owing to nonadherence are estimated at $8.5 billion in otherwise unnecessary spending.16 Other effects of nonadherence are huge indirect costs, one of which is lost workdays, which increases the cost of manufacturing.16 Table 1 lists the negative economic consequences of nonadherence.

| 4 |

are beginning to look at the health status of their workforce from a new perspective — as an investment.

Table 1.— Economic Burden of Nonadherence with Medications.16 d

Need for additional medical treatment;

d

Need for additional medications;

d

Additional hospital/nursing home admis-

It is becoming clear that improved drug therapies for ill workers can substantially improve productivity and therefore the bottom line of employers (see Table 2). There is a growing trend by employers to factor productivity goals into health benefit decisions.17 Innovative employers across America are producing definitive data on the ways health, illness, and medical treatment affect productivity.

sions or readmissions; d

Absenteeism or reduced productivity at work; and

d

Mortality costs (including direct and indirect

Table 2.—Causes of Reduced Worker Productivity Due to Illness.

costs associated with lost earnings). Pharmaceutical companies are responding to the need for better patient adherence by developing new medications or new forms of existing medications with improved side effect profiles, less frequent dosing requirements, or both. For example, patients with osteoporosis used to take alendronate (FosamaxF) each morning upon rising. They were instructed to have nothing to eat or drink for a half hour, nor could they lie down during that period. Now the product is available in a preparation to be taken (with the same restrictions) once weekly. It is anticipated that this streamlined dosage schedule will foster greater adherence. Similarly, in February 2001, a once-weekly dosage form of fluoxetine (ProzacF) was approved by the Food and Drug Administration. These and other improved dosage forms can improve patient adherence to medication regimens, improve treatment outcomes and thereby increase workforce productivity.

d

Loss of optimal efficiency

d

Use of sick days

d

Lost time in caring for ill child or dependent

d

Work-related injury or disability resulting from illness

New medications offer the potential to reduce overall health care costs by replacing more expensive and invasive medical treatments. A recent study by Columbia University economist Frank Lichtenberg18 used large public databases containing individual patient records on use and costs of health care services to ask the question, "Are the benefits of these newer drugs worth their cost?" He found that people consuming newer medicines in 1996 experienced fewer deaths and fewer work-loss days than people consuming older medications. The use of newer drugs tended to lower all types of nondrug medical spending, resulting in a net reduction in the total cost of treating a given condition. The overall reduction in medical expenditures from using a newer drug was found to be about four times greater than the added cost of that drug.

New Pharmaceuticals Reduce Treatment Costs and Improve Workplace Productivity A healthy and productive workforce can provide a strong competitive advantage for companies operating in today’s business world. Some corporate leaders

| 5 |

The prevalence and annual cost burden of the leading illnesses (excluding work-related injuries) that compromise workplace productivity and contribute to lost wages are listed in Table 3. These diseases account for at least $422 billion annually in total health care costs.

Table 3.— Prevalent and Costly Illnesses* Disease

Prevalence (million)

Direct Cost ($ billion)

Indirect Cost ($ billion)

Total Cost ($ billion)

Allergic rhinitis

20-40

5.9

4.6

10.5

Arthritis

43

15

50

65

Asthma

14

5.1

2.7

7.8

Diabetes

16

44

54

98

Depression

18.8

12.4

31.3

43.7

Heart failure

2-3

19.4

32.6

52

Hypertension

50

17

7

24

Coronary heart disease

12.4

53.4

47.4

100.8

Migraine

11-18

1

13

14

27

5

1

6

Peptic ulcer disease

*See below for further discussion and references. For many of the diseases listed in Table 3, the indirect costs of lost productivity due to absenteeism, disability, premature mortality, and lost wages are substantial and in some cases exceed the direct costs of treatment (Figure 3).

Figure 3

Percentage of Total Costs

Direct and Indirect Costs of Major Illness in the Workplace* 100% —

50% —

Peptic Ulcer Disease

Hypertension

Asthma

Allergic Rhinitis

Coronary Heart Disease

Diabetes

Depression

Arthritis

Migraine

0% —

Indirect costs: Costs of lost productivity due to absenteeism, disability, premature mortality, lost wages Direct costs: Health care costs including hospitalizations, physicians, drugs, etc.

*See following for further discussion and references.

| 6 |

For individuals with cardiovascular disease, the drug costs are often far lower than the productivity and health costs. The relative proportions of these costs for several cardiovascular diseases are illustrated in Figure 4.

Figure 4 Drug Costs, Health Care Costs, and Productivity Costs of Cardiovascular Diseases $120 —

Drugs

Billions of Dollars

100 — 80 —

Health Care

60 —

Productivity

40 — 20 —

Source: American Heart Association Heart and Stroke 2000 Statistical Update: www.americanheart.org/statistics/economic

0—

Coronary Heart Disease

Stroke

Hypertension

Congestive Heart Failure

The use of prescription medicines has the potential to improve worker productivity by reducing the direct and indirect costs of major illnesses. In a 1996 study using nationally representative data from 1987 government surveys, Rizzo and colleagues19 estimated the effects of prescription medicines on hourly wages and on days lost from work for workers with hypertension, heart disease, type 2 diabetes, and depression. The net benefits to employers from having workers take prescription medications for these chronic diseases were substantial. Assuming average rates of compliance with medication regimens, the annual net savings amounted to $286 per hypertensive employee, $633 per employee with heart disease, $822 per depressed employee, and $1475 per employee with diabetes. The authors concluded: "These estimated net benefits accrue because prescription medicines substantially lower absenteeism among chronically ill workers." Importantly, Rizzo and colleagues19 found that "for all chronic conditions examined, estimated employer costs for prescription medications were outweighed by increased revenues resulting from enhanced employee productivity." Similarly, a Massachusetts Institute of Technology study of depression, anxiety, migraine, and hypertension in individuals employed as insurance claims processors showed that for each of these diseases the number of hours worked in a 2-week interval increased after pharmaceutical treatment.20 In addition, the number of claims processed by these claims processors (i.e., productivity) also went up after treatment (see Figure 5).

| 7 |

Figure 5 Pharmaceuticals Improve Productivity

Hours worked over 2 week period

70 68 66 64 62 60 58

Depression

Anxiety Pre-Treatment

Migraine

Hypertension

Post-Treatment

Source: Ernie Berndt, "Illness and Productivity: Objective Workplace Evidence," MIT Working Paper, May 1997

to indirect costs.23 A poll by Louis Harris & Associates for USA Today (August 7, 1999) found that over half of adults reported suffering from a related disorder (sinus problems); 34% of sufferers said the condition affects work performance.

Newer drugs can reduce the cost of illness and result in productivity gains. Ten diseases prevalent in the workplace are discussed below (see Table 3). In each case, therapy with medications, especially newer medications can significantly improve the health and productivity of ill employees.

Benefits of drugs. The first-generation and some second-generation antihistamine preparations used for these conditions cause sedation, variously described as drowsiness, fatigue, and altered cognitive and psychomotor function. The new, less sedating antihistamines avoid these central nervous system side effects because they do not cross the blood-brain barrier.

Allergic rhinitis Disease burden. Seasonal allergic rhinitis (hay fever) affects an estimated 13 million working adults and causes absenteeism and diminished work productivity.21 Estimates of at-work productivity losses range from $2.4 to $4.6 billion,22 much of which comes not from absence due to allergies but from lost productivity due to the sedating effects of the older medications used to treat them.

Compared with nonsedating agents, sedating antihistamines have been linked to more workplace accidents and injuries21 as well as to impaired work performance.24,25 A study of productivity in clerical workers (insurance claims processors) with aller-

When patients self-manage allergic rhinitis with older, more sedating antihistamines, lost productivity and missed workdays add $3.8 billion yearly

| 8 |

gies found that the productivity of workers using sedating antihistamines was 13% lower than the productivity or workers using nonsedating antihistamines.24 This lost productivity was calculated to cost the employer $9.00 daily for each employee taking sedating antihistamines. Assuming a greater daily cost of up to $1.50 for nonsedating antihistamines, this translates to a favorable cost/benefit ratio.25 Similarly, the William M. Mercer employee benefits consultant company used an actuarial model to calculate that many employers can realize a net financial gain of $2.00 to $4.00 for every $1.00 spent when allergy sufferers use nonsedating instead of sedating treatments.26 The savings result from a combination of productivity gain, fewer accidents and disability claims, and less sick leave.

Arthritis Disease burden. In the United States, arthritis and related conditions affect nearly 43 million individuals and are a major cause of disability.27 The total annual cost for arthritis is estimated at $65 billion each year; $15 billion in direct costs and $50 billion in indirect costs, largely resulting from lost wages.28 Benefits of drugs. Treatment for the various types of arthritis (osteoarthritis, fibromyalgia, and rheumatoid arthritis are the leading forms) has been centered around the use of nonsteroidal anti-inflammatory drugs (NSAIDs), either alone or combined with disease-modifying anti-rheumatic drugs for rheumatoid arthritis. One of the drawbacks to long-term

treatment with NSAIDs is the potential for damage to the stomach lining. A relatively new class of NSAIDs has emerged: the cyclo-oxygenase-2 (COX-2) inhibitors. These agents relieve the pain and inflammation of osteoarthritis and rheumatoid arthritis, while largely avoiding gastrointestinal toxicity. These agents also have potential positive and negative cardiovascular effects, but more research is needed to clarify the clinical significance of these actions. A study was undertaken to model the economic efficiency of nonselective (i.e., conventional) NSAIDs used in combination with gastroprotective agents with the economic efficiency of a selective COX-2 inhibitor alone, in the treatment of arthritis.29 The investigators found that the COX-2 inhibitor had significant tolerability and safety advantages compared with nonselective NSAIDs. The risk of gastrointestinal adverse events with the COX-2 inhibitor was similar to or less than that observed when nonselective NSAIDs were given in combination with gastroprotective agents. The investigators concluded that use of the selective COX-2 inhibitor is expected to significantly reduce the economic costs of treating arthritis by reducing gastrointestinal toxicity and its associated morbidity. In terms of work loss and productivity, a great deal can be gained by keeping patients free from the serious gastrointestinal injury associated with older antiarthritic drugs. Those who have had to limit their use of arthritis medications to avoid side effects can now seek relief from constraining or incapacitating pain.30

| 9 |

Asthma Disease burden. More than 14 million individuals in the United States are affected by asthma.31 The prevalence of and morbidity and mortality from asthma have increased over the past 20 years for reasons that are not clear.32 The direct and indirect costs attributed to asthma also are rising. In the United States, these costs were estimated at $6.2 billion in 1990.33 They rose to $7.8 billion in 1994.34 The indirect medical costs (missed work or school and restricted activity) were estimated at $2.7 billion. The remaining $5.1 billion was attributed to direct medical costs (ambulatory care visits, hospital outpatient and inpatient services, emergency department visits, physician fees, and prescription medications). Asthma is one of the few medical conditions in which direct medical costs are greater than indirect costs. Benefits of drugs. For years, asthma was attributed to airway constriction (bronchospasm) that led to airway obstruction, and bronchodilators were the agents of choice. Now, the disease is considered primarily an inflammatory disease, and anti-inflammatory agents are preferred for long-term control. Inhaled corticosteroids are

recommended for moderate to severe disease. Donahue and associates35 found that inhaled corticosteroids protect against exacerbations of asthma that lead to hospitalization. A Saskatchewan study36 determined that the regular use of low-dose, inhaled corticosteroids is associated with a decreased risk of death from asthma. Balkrishnan and colleagues37 reported a 50 percent decrease in hospitalization rates and a 26 percent decrease in outpatient visits and concluded that the introduction of inhaled corticosteroids reduced total health care costs by 24 percent. A study by Ozminkowski and coworkers38 suggested that using inhaled corticosteroids, cromoglycate, or nedocromil to control airway inflammation is a less costly approach than using other drugs to control asthma. They noted that asthma-related expenditures would be higher if inhaled anti-inflammatory medications were used, but total health care costs would be reduced by nearly $950 per patient per year. Since these studies were completed, newer drug treatments for asthma have emerged, such as leukotriene antagonists and more potent inhaled corticosteroids, which may further reduce the use of other more costly services.

Diabetes Disease burden. It is estimated that 16 million Americans have diabetes, with nearly 800,000 cases diagnosed annually; about 10 million Americans have the disease and do not know it.39 Diabetes is the nation’s seventh leading killer and accounts for $98 billion in direct and indirect medical costs and lost productivity each year.40 In 1997, $44 billion was spent on direct medical costs for diabetes; the remaining $54 billion was allocated to indirect medical costs (disability, work loss, and premature mortality).41

| 10 |

A study42 was conducted that measured labor force participation, hours of work lost, and the economic value of those lost work hours in employed persons with diabetes. The researchers found that loss of yearly earnings, on average, amounted to about a one-third reduction in earnings. The authors of a 1998 Harvard study on the benefits of glucose control through drugs and dietary treatment43 observed that "lost productivity, increased absenteeism, and increased use of health resources associated with poor glycemic control should provide a strong incentive for demanding more comprehensive management from the health care provider organization than what is currently offered." Specific findings are shown below.

Economic and Quality-of-Life Benefits of Glucose Control with Diet and Drug Therapy43 d

Higher retained employment (97% vs. 85% with no treatment)

d

More stay fully productive (99% vs. 87% with no treatment)

d

The second-generation sulfonylurea agent glipizide is now available in an extended-release formulation for the treatment of diabetes. Monthly productivity losses related to absenteeism improved slightly or did not change significantly in patients receiving extended-release glipizide, and differences in direct health care costs among patients receiving conventional glipizide, metformin, or acarbose were small.45 The extended-release glipizide formulation provided more stable plasma drug concentrations than the conventional formulation, and the oncedaily regimen may improve patient adherence.

Lower absenteeism ($90 monthly savings/worker)

d

Fewer bed days ($300 savings/1000 person days)

d

Fewer restricted activity days ($1600 savings/1000 person days)

using two of the newer agents for type 2 diabetes (metformin and troglitazone), showed distinct advantages were achieved by combining these drugs, which are from different classes.44 One drug acts by decreasing the body’s production of glucose and the other by increasing the rate at which glucose is removed from the blood stream and delivered to body tissues, where it is needed. Although the thiazolidinedione, troglitazone, has been withdrawn from the market because of serious problems with liver toxicity, two other drugs in this class with similar beneficial effects but a reduced likelihood of adverse effects are now available.

Depression Benefits of drugs. Today, there are six classes of diabetes drugs that act through different mechanisms: insulin, sulfonylureas, biguanides, alpha-glucosidase inhibitors, meglitinides, and thiazolidinediones. One study,

Disease burden. Major depression is a leading cause of disability in the United States.46 An estimated 9.5 percent of Americans 18 years of age and older suffer from depression in any given year. In 1998, some 18.8

| 11 |

million people were believed to have depression. Nearly twice as many women (12%) as men (7%) are affected by a depressive disorder. In one study,47 the average duration of disability and the disability relapse rates were greater for depressive disorders than for other common chronic medical conditions. Depression is the costliest modifiable risk factor for increased health care expenditures. Goetzel and colleagues48 reported that among 10 modifiable health risks, depression had the greatest impact on employee medical expenditures. But depression is a largely treatable disorder; more than 80 percent of patients improve when they receive appropriate treatment. Estimates have been developed for three major cost categories of depression49: (1) direct costs of medical, psychiatric, and pharmacologic care; (2) mortality costs arising from depression-related suicides; and (3) morbidity costs associated with depression in the workplace. These researchers estimated that the annual cost of depression in the United States in 1990 was approximately $43.7 billion, including $12.4 billion (28%) in direct, treatment-related costs; $7.5 billion (17%) in suicide-related costs; and $23.8 billion (55%) for excess absenteeism and reduced productive capacity while at work during episodes of depression. Kessler and Frank50 reported that the effects of psychiatric disorders on work loss are similar across all occupations, while effects on work cutback are greater among professional workers than those in other occupations. The investigators found that major depression was by far the most prevalent psychiatric disorder. Benefits of drugs. Antidepressant medications influence the functioning of brain neurotransmitters. Newer drugs, includ-

ing selective serotonin reuptake inhibitors (SSRIs) and agents that influence reuptake of norepinephrine and dopamine, tend to have fewer side effects than older drugs, which include tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors. Newer and older antidepressants are all effective in relieving depression. However, some individuals respond to one type of drug, but not to another. Therefore, newer medications should be additions to, not replacements for, older medications in formularies. Other types of antidepressants are currently in development. In a real-world study on treatment costs for SSRIs versus TCAs,51 the researchers made sophisticated econometric adjustments for factors that influence drug choice and expenditures. Once these adjustments were made, they found that total direct health care expenditures were significantly lower for SSRI users than expenditures for users of the older medications. A study on the effects of chronic depression and its treatment on workplace performance52 found that the more severe the depression, the lower the level of perceived at-work performance. In addition, the researchers found that a reduction in depressive severity improves the patient’s perceived work performance. The researchers noted that after implementation of treatment, improvement in work performance was rapid, with two thirds of the change occurring by the fourth week of treatment. The relationship between depression and work performance was studied in a large clinical trial.53 Eighty-six percent of patients treated with antidepressant medications reported some improvement after 4 weeks. The extent of work performance improvement correlated highly with the improvement in depressive symptoms.

| 12 |

Compared with older medications, SSRIs have been found to make greater contributions to improved productivity; and twice as many patients on older medicines discontinued treatment. SSRIs have a better side effect profile, leading to more continuous use and better patterns of adherence to clinical practice guidelines for depression care.54,55 This in turn may lead to more cost-effective care.

Heart Failure Disease burden. Some 2 to 3 million Americans have heart failure, and 400,000 new cases are diagnosed each year.56 Heart failure causes 39,000 deaths a year and is a contributing factor in another 225,000 deaths. Mortality due to heart failure is more common among men than women and is twice as high for African Americans than for whites in all age groups. The risk of heart failure increases with age. More people are living and working longer so heart failure has a growing impact on worker productivity. The total cost of heart failure in the United States is estimated at $52 billion per year.57 The presence of coronary disease is among the greatest risk factors for heart failure. Although a single risk factor may be sufficient to cause heart failure, a combination of factors dramatically increases the risk. Common risk factors are coronary disease, irregular heartbeat, high blood pressure, elevated blood cholesterol, tobacco use, physical inactivity, poor nutrition, obesity, and diabetes.58

total indirect cost of ischemic heart disease to employers in private industry was $182.74 per enrollee, and 95 percent of this indirect cost was the consequence of work loss due to morbidity, rather than mortality. Benefits of drugs. In most cases, a cure for heart failure is not possible. Lifestyle modifications and drug therapy are used to manage symptoms and prolong life. A treatment program for heart failure usually requires rest, proper diet, modified daily activities, and medications that include angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, digitalis, diuretics, or vasodilators. The various medicines for heart failure have different functions. ACE inhibitors and vasodilators dilate (expand) blood vessels and decrease resistance, permitting blood to flow more easily and thus making the heart’s pumping action easier and more efficient. These medications have been shown to reduce mortality from heart failure, delay the progression of the disease, improve functional status, and decrease the need for hospitalization.60,61 Betablockers, once used with care in patients with heart failure, have been shown to slow the progression of heart failure and reduce hospitalization and mortality.62,63 Digitalis increases the force of the heart’s contractions, helping to improve circulation.

An analysis of a proprietary claims database of 3.1 million insured individuals was performed to examine the indirect costs of ischemic heart disease, a condition in which there is coronary artery blockage.59 The conclusions of this report, published in 2001, are that the

| 13 |

Diuretics help reduce the amount of fluid in the body and are helpful for patients with fluid retention and hypertension. Because heart failure can be managed (but not cured) using a combination of drugs from several different classes, it is important that a variety of drugs be carried on formularies, with particular attention being paid to new drugs, especially those in the ACE inhibitor and beta-blocker classes. New research has shown that patients with congestive heart failure who received a new beta-blocker plus standard treatment were 35% less likely to die than those who received just standard treatment.64

Hypertension Disease burden. Hypertension (high blood pressure) is an extremely common disorder that affects about 50 million people in America.65 The total cost of hypertension in the United States is estimated to be $24 billion annually, of which $17 billion are direct costs and $7 billion are indirect costs.66

Hypertension is more common as people grow older, and it is more serious among African Americans. Nine out of every 10 people with hypertension have no identifiable cause. Often called the "silent killer," hypertension can lead to serious health problems (or even death) without causing symptoms. People with untreated hypertension are much more likely than those with normal blood pressure to die from or be disabled by cardiovascular complications such as strokes, heart attacks, heart failure, irregular heartbeat, and kidney failure. A 19-year follow-up study,67 begun in 1972, linked 10,284 normotensive (diastolic blood pressure [DBP] less than 95 mm Hg), mildly hypertensive (DBP 95—104 mm Hg), and severely hypertensive (DPB greater than 104 mm Hg) individuals in Finland with national registries covering hospital admissions, use of major drugs, absence due to sickness, disability pensions, and deaths. The mean undiscounted total costs (in U.S. dollars at 1992 prices) were $132,400 among normotensive men, $146,400 among mildly hypertensive men, and $219,300 among severely hypertensive men. More than 90 percent of total costs were indirect productivity losses. If these results were extrapolated to the entire U.S. population with hypertension (50 million people), the costs would be staggering. Benefits of drugs. Only one in four patients with hypertension receives treatment,68 yet this disease can be treated successfully. A wide variety of medications are available for the treatment of hypertension. It is a matter of finding the specific drug that will best suit an individual patient (see Table 4). A recent report by the American Heart Association69 points out that with so many antihypertensive agents to choose from, those that provide benefits beyond

| 14 |

decreasing blood pressure will become the preferred therapies. The American Heart Association states that angiotensin II receptor antagonists have a very favorable side effect profile, and that "these drugs may become the preferred agents of physicians who factor indirect costs – less morbidity and greater productivity – into their selection of an antihypertensive therapy."

Table 4. — Types of Drugs Used to Manage Hypertension68

Therapeutic Class

Effects of Drugs in Class

Diuretics

Increased urination to reduce salt and water retention and lower blood volume

Beta-blockers

Slowing of heart rate and lowering of cardiac output

Angiotensin-converting enzyme inhibitors

Blockade of production of angiotensin II, the hormone that causes arteries to contract; stimulation of release of another hormone that causes kidneys to retain water

Angiotensin II receptor antagonists

Relaxation of blood vessels by blocking the vasoconstrictive action of angiotensin

Calcium channel blockers

Expansion of blood vessels by slowing the entry of calcium into cells; some agents in this class increase heart rate somewhat, whereas others slow it a little

Alpha-1 blockers

Blockade of the effect of constricting hormones such as norepinephrine

Alpha-2 agonists

Decreased action of the nervous system in constricting blood vessels; works in the brain

Direct vasodilators

Relaxation of artery walls

Sympathetic nerve blockers

Prevention of nerves from constricting blood vessels

Coronary heart disease (CHD) Disease burden. Coronary heart disease (CHD), which includes myocardial infarction and angina pectoris, afflicts 12.4 million Americans and is the leading cause of premature, permanent disability in the workforce.69 Total estimated expenditures for CHD in 2001 are $100.8 billion; direct costs are $53.4 billion, with pharmaceuticals accounting for only 6% of these costs. Lost productivity due to morbidity and mortality from CHD will cost employers $47.4 billion.69 Studies show overwhelmingly that the risk of developing CHD is related to elevated levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C or "bad cholesterol"). High cholesterol is the most prevalent condition among American workers, affecting about 30% of the workforce.70 Cholesterol levels are uncontrolled in 67% of these individuals, although levels can generally be modified with diet, exercise, and medications.

| 15 |

Benefits of drugs. Four classes of drugs are used to treat elevated levels of cholesterol: statins, niacin, bile acid resins, and fibrates. The statins, which reduce cholesterol synthesis by inhibiting HMG CoAreductase (an enzyme associated with cholesterol production), have proven to be highly effective in lowering cholesterol levels. The cholesterollowering effects of the statins are associated with large decreases in LDL levels, deaths from CHD, and nonfatal myocardial infarctions.71,72 The statins provide an example of the benefits of gradual improvements in a drug class. The newer statins are considerably more potent than the earlier ones in reducing serum LDL-C and are an effective treatment for patients with severe hypercholesterolemia. The earlier, less potent statins may nevertheless be adequate for individuals who have mildly elevated serum cholesterol and are at low risk of coronary heart disease. The statins vary in price and in their effects on highdensity lipoprotein cholesterol (HDL-C) and serum triglycerides. Thus, the availability of a range of statins enables physicians to treat the individual patient with precision and at the lowest cost. Despite the general public awareness about the dangers of high cholesterol and CHD risk, many patients still are not receiving and following the recommended treatment. Although 17 million Americans are candidates for drug therapy for CHD, it is estimated that only 5.3 million actually receive therapy.73 In addition, it has been estimated that 50 percent of patients using

lipid-lowering medications stop taking the drug within the first year. After two years, compliance falls to 25 percent.74 Data from studies attribute treatment failure rates to inadequate physician treatment and lack of implementation of current cholesterol programs.

Migraine Disease burden. In the United States, an estimated 11 to 18 million individuals, most of them women, suffer from migraine disease.75 There is no known cure for migraine, only treatments for symptoms. Migraine disease has many symptoms, including nausea, vomiting, auras (light spots), sensitivity to light and sound, numbness, difficulty in speech, and severe semihemispherical head pain; a migraine attack can last for 8 hours to (in severe cases) several days, even weeks. Migraine is caused when a physiological trigger or triggers cause vasodilation (expansion) of the cranial blood vessels. Controllable triggers include bright light, aspartame, alcohol, and some foods such as fish and aged cheese. Uncontrollable triggers include weather patterns and menstrual cycles. Migraine costs U.S. employers about $13 billion a year due to missed workdays and impaired work function.76 Close to $8 billion of that cost is directly due to missed workdays. Annual direct medical costs for migraine are about $1 billion, making the overall health care cost $14 billion. One study77 determined that work effectiveness was reduced 41 percent for people with migraine headaches and 24 percent for people with other types of headaches. Some $100 is spent per diagnosed patient, and physician office visits account for about 60 percent of all direct costs. Benefits of drugs. Recently introduced drugs are reported to be effective against migraine headaches. Sixty-eight percent

| 16 |

of patients with migraine responded to treatment with sumatriptan, a new drug that works on the neurotransmitter serotonin.78 A study of the benefit/cost ratio of sumatriptan for the treatment of migraine found that that the benefits (i.e., the reduction in labor costs and decrease in lost productivity) exceeded the costs by 10-fold (see Figure 6).

Figure 6 Migraine Medication Reduces Employers’ Labor Costs and Decreases Lost Productivity $500 —

Cost per Employee per Month

$400 —

Peptic ulcer disease (PUD) and gastroesophageal reflux disorder (GERD) are two of the most common and costly gastrointestinal disorders. Pharmaceutical advances have led to the development of the proton pump inhibitors (PPIs), a class of highly effective prescription medications that control stomach acid and promote healing for both disorders. Nonprescription drugs are widely used for heartburn and other symptoms of GERD and peptic ulcers. However, the greater effectiveness of prescription medications and the cost-effectiveness of PPI treatment even for mild cases of GERD suggest that using prescription rather than nonprescription therapies may result in savings.

$435 PUD disease burden. At least once in a lifetime, 1 in 10 Americans suffers from PUD.81 Annual health care costs have been estimated at nearly $6 billion: $5 billion in direct costs ($3 billion in hospitalization costs, $2 billion in physician office visits) and $1 billion in decreased productivity and increased absenteeism. Every year there are some 500,000 to 850,000 new cases of PUD in the United States, and more than one million hospitalizations.

$300 —

$200 —

$100 —

$0 —

Gastrointestinal Disorders

$44 Cost of Drug Treatment for Migraine

Reduction in Labor Costs and Decrease in Lost Productivity

Source: Legg RF, et al., "Cost Benefit of Sumatriptan to an Employer," Journal of Occupational and Environmental Medicine, Vol. 39, No. 7, July 1997.

A study by Schulman and associates79 placed dollar figures on the effectiveness of sumatriptan administered to migraineurs in the workplace. The authors found that there was a labor savings of $600 per patient per year. Similarly, in a placebo-controlled trial examining patients with four moderate to severe migraine attacks, those receiving the migraine drug rizatriptan reported 0.7 fewer hours of paid work missed due to absenteeism and 0.4 fewer hours of productive time lost on the job.80

In the past 20 years, we have learned that 9 out of 10 peptic ulcers are caused by an infection with the microorganism Helicobacter pylori (H. pylori), a spiral-shaped bacterium found in the stomach. In the United States, H. pylori is seen more often in older adults, African Americans, Hispanics, and persons in lower socioeconomic groups. H. pylori infection can cause chronic active, chronic persistent, and atrophic gastritis in adults and children.82 Infected individuals have a two- to sixfold increased risk of developing gastric cancer.

| 17 |

Benefits of drugs for PUD. Before the discovery of H. pylori in 1982, spicy food, acid, stress, and lifestyle were considered the major causes of ulcers. Most patients were prescribed acid-suppressing medications such as histamine-H2 receptor blockers or PPIs on a long-term basis. These drugs relieved ulcer symptoms and healed gastric mucosal inflammation. Sometimes they healed the ulcer, but they did not treat the infection. When acid suppression is stopped, the majority of ulcers recur, especially those caused by H. pylori. H. pylori infection can usually be cured with a short course of antibiotics. With this treatment, the ulcer is cured and does not recur in more than 80 percent of patients.81

GERD disease burden. GERD is a common, chronic, relapsing condition where gastric acid irritates and often damages the esophagus. It is estimated that 18.6 to 21 million adults suffer from GERD. The main symptom of this disease is heartburn, and it is estimated that 60 million Americans suffer heartburn at least on a monthly basis.84 One large HMO found the direct cost of medical treatment for GERD to be $471 per adult, not including over-the-counter medications, among those receiving drug therapy.85 If untreated (or treated inappropriately with over-the-counter medications), GERD may lead to recurring heartburn, significant chest pain, and a higher likelihood of esophageal cancer.

Therapy for H. pylori infection consists of 10 days to 2 weeks of one or two effective antibiotics, such as amoxicillin, tetracycline, metronidazole, or clarithromycin, as well as ranitidine bismuth citrate, bismuth subsalicylate, or a PPI.82 Longer durations of treatment (14 days versus 10 days) provide better eradication rates, as do triple-drug regimens compared with two-drug regimens or monotherapy. As of February 2001, the Food and Drug Administration had approved eight treatment options for the eradication of H. pylori infection.82

Benefits of drugs for GERD. Until recently, treatment for GERD usually involved a combination of over-the-counter antacids and the use of H2-receptor antagonists such as cimetidine or ranitidine to control stomach acid. In recent years, however, PPIs have been widely used because they are substantially more effective at controlling stomach acid, leading to faster healing of the esophagus, better symptom relief for all grades of esophagitis, and longer periods between relapse.86

H. pylori eradication therapy has been shown to be cost-effective in a managed care setting. A study undertaken in a large HMO by Levin and colleagues83 reported that total 12-month costs in a group treated with antibiotics for H. pylori infection were $285 per person less than the costs in untreated patients. The eradication of H. pylori in patients with PUD resulted in decreased use of outpatient services and decreased cost of follow-up care.

Although more expensive than the older H2-receptor agents, in most circumstances PPIs are often more cost-effective because of their superior ability to relieve symptoms.87,88,89,90,91 One study of prescribing strategies for treating moderate to severe GERD found that the most cost-effective plan was initial treatment with PPIs followed by additional PPI therapy as symptoms recur. This strategy achieved cost savings by substantially reducing the need for the diagnostic endoscopies that other management strategies require before a PPI can be prescribed.92

| 18 |

Cost Savings through Disease Management and Practice Guidelines Disease management is a multidisciplinary, continuum-based approach to health care delivery that evolved from a failed experiment in cost control: health care component management (e.g., limiting formulary choices, reducing the number of diseases covered). Disease management programs proactively identify populations with, or at risk for, chronic medical conditions. They are designed specifically to target populations with high-cost conditions for which a substantial gap exists between the implementation of guidelines for care and how patient care is actually provided.93,94 They focus on both quality of care and costs.95,96 Pharmaceutical intervention is the keystone of any disease management program. Even though medication use may increase, disease management programs control costs through improved clinical outcomes. Examination of three common medical conditions — asthma, diabetes, and congestive heart failure — shows the benefits of disease management. In all three cases, optimal use of pharmaceutical agents is crucial to both improving outcomes and controlling costs. Asthma. By encouraging the appropriate use of medications in patients with asthma in Georgia and Florida, CIGNA HealthCare reported a 23 percent reduction in hospital admissions and a 15 percent improvement in appropriate medication usage.97 The Virginia Health Outcomes Partnership (VHOP), the first disease management program for Medicaid patients, incorporated disease management intervention and trained physicians in the appropriate use of state-of-the-art asthma therapy. VHOP also trained health care providers in methods for teaching patients how to effectively control their asthma.97 It was estimated that the program would have saved

$1.2 million in emergency claims had it been implemented statewide. Congestive heart failure. A congestive heart failure management program in Sacramento, California, reduced hospital admissions and readmissions by 80 percent.98 The Northeast Ohio office of United Health Care of Ohio Inc. is receiving encouraging results in its congestive heart failure disease management program, reporting a 52 percent reduction in hospitalizations. A study of a heart failure outpatient management program in Portland, Oregon, demonstrated that total hospital admissions for cardiovascular causes decreased by 59 percent and total emergency room visits decreased by 77 percent.99 Disease management programs for diabetes are under way across the country.100 In Arizona, a review of a random sample of patients in six Medicare managed care plans that comprise 40 percent of the Medicare population determined that the mean number of physician office visits fell 13 percent after disease management intervention that included use of pharmaceuticals.101 There are many ways to manage health plan costs without merely restricting access to new medicines. According to a report in Disease Management News, PacifiCare of Colorado achieved striking results with its low-cost disease management

| 19 |

Figure 7 Impacts of Disease Management on Congestive Heart Failure Patients — Net Savings: $2900 per patient102 30% —

27% 18%

20% — 10% — 0% — -10% —

Use of ACE Inhibitors

Rate of Hospitalization

Avg. Length of Hospital Stay

-36.1%

-33.7%

Use of Diuretics

-20% — -30% — -40% — program for patients with congestive heart failure. By focusing on extensive use of clinical guidelines, case management, and patient counseling, the program reduced both the rate of hospitalization and the length of hospital stay, and achieved a net savings of $2900 per patient (see Figure 7).102

productivity and avoided sick wages saved in 2001 (see Figure 8).104 Optimal drug treatment protocols were an integral element of these HEDIS measures.

In addition to savings in health care costs, productivity improvements can also result when pharmaceuticals are used according to currently accepted standards endorsed by clinicians and quality review organizations. The National Committee for Quality Assurance (NCQA) report State of Managed Care Quality, 2001 makes it clear that high-quality health care, including pharmaceutical therapy, returns economic benefits in the form of less absenteeism and improved productivity.103 Using its Health Employer Data and Information Set (HEDIS) measures of quality treatment for specific diseases, NCQA noted that over the past several years there has been an improvement in the treatment of employees having seven key diseases . As a result, U.S. employers will enjoy an annual productivity dividend of 8 million sick days avoided and $1.4 billion in improved

| 20 |

Figure 8 Productivity dividends resulting from adherence to seven key HEDIS measures in 2001 Sick/unproductive days avoided

Wages saved ($ millions)

Heart disease

2,900,000

$501

Asthma

1,970,000

$337

Hypertension

1,000,000

$171

Chicken Pox

948,000

$163

Depression

640,000

$110

Diabetes

575,000

$99

Smoking

147,000

$25

8,180,000

$1,406

Total Source: NCQA104

CO N C LU S I O N S Maintenance of the health status of a company’s workforce is an investment in human capital. Because pharmaceuticals are generally the most effective means for improving health status, programs that make state-of-the-art medications available to employees represent an essential strategy. Drug therapies can bring the benefits of increased productivity, individualized and optimized patient care, savings in overall health care costs, and improved quality of life and satisfaction for employees. Evidence reveals that new drugs should be made available to individuals covered by health care plans because such drugs may decrease productivity losses and may lower total health care costs.

Accordingly, benefit plans should be designed to include enough drugs in each therapeutic class to better match therapy to patient needs. Individual patients can differ greatly in their response to medicines due to variations in physiology, age, gender, ethnic background, and other factors. Improved versions of medicines usually provide advantages over existing agents, including greater effectiveness, safety, and dosage convenience. The test of the value of new pharmaceutical products should be whether they help keep people healthy and active. This translates to greater productivity for individuals in the workforce. Disease management programs have the potential to produce increased savings and improved health outcomes.

The National Pharmaceutical Council (NPC) is supported by more than 20 of the nation’s major research-based pharmaceutical companies. NPC sponsors a variety of research and education projects aimed at demonstrating that the appropriate use of pharmaceuticals improves both patient treatment outcomes and the cost effective delivery of overall health care services.

| 21 |

20. Berndt E. Illness and Productivity: Objective Workplace Evidence. MIT Working Paper, May 1997.

REFERENCES 1. Dubois RW, Chawla AJ, Neslusan CA, et al. Explaining drug spending trends: Does perception match reality? Health Affairs. 2000;19(2):231-9.

21. Fireman P. Treatment of allergic rhinitis: effect on occupation productivity and work force costs. Allergy Asthma Proc. 1997;18(2):63-7.

2. Suh DC, Lacy CR, Barone JA, et al. Factors contributing to trends in prescription drug expenditures. Clin Ther. 1999;21:1241-53. 3. Sherman D, Bradshaw A, Tanamor M, Topoleski C. Factors Affecting the Growth of Prescription Drug Expenditures. Washington, DC. National Institute for Health Care Management Research and Education Foundation; July 9, 1999. 4. Dandow D. Increasing access to pharmaceuticals. The Freeman. 1996;46(2). Available at: http://fee.org/freeman/96/9602/bandow.html. Accessed May 31, 2001. 5. Horn SD, Sharkey PD, Tracy DM, et al. Intended and unintended consequences of HMO cost-containment strategies: results from the managed care outcomes project. Am J Manag Care. 1996;2(3):253-64.

22. Crystal-Peters J, Crown WH, Goetzel RZ, et al. The cost of productivity losses associated with allergic rhinitis. Am J Manag Care. 2000;6(3):373-8. 23. Seggev JS. Allergy, Allergic Rhinitis, and Asthma. UMC (University Medical Center of Southern Nevada) Respiratory Symposia. Available at: http://www.umccares.org/health_info/allergy_asthma.asp. Accessed September 5, 2001. 24. Cockburn IM, Bailit DMD, Berndt ER, Finkelstein SN. Loss of work productivity due to illness and medical treatment. J Occup Environ Med. 1999;41:948-953. 25. Cockburn IM, Bailit DMD, Berndt ER, Finkelstein SN. When antihistamines go to work. Bus Health. 1999;March:49-50.

6. Horn SD, Sharkey PD, Phillips-Harris C. Formulary limitations and the elderly: Results from the managed care outcomes project. Am J Manag Care. 1998;4(8):1105-13.

26. Measuring the Value of the Pharmacy Benefit: Allergy as a Case Example. William M. Mercer, Inc., 2000. 17 pp.

Sloan FA, Gordon GS, Cocks DL. Hospital drug formularies and use of hospital services. Med Care. 1993;31:851-67.

27. Centers for Disease Control and Prevention. National Center for Chronic Disease Prevention and Health Promotion. Chronic Disease Prevention. Arthritis. Available at: http://www.cdc.gov/nccdphp/arthritis.htm. Accessed May 3, 2001.

8. Soumerai SB, McLaughlin TJ, Ross-Degnan D, et al. Effects of limiting Medicaid drug-reimbursement benefits on the use of psychotropic agents and acute mental health services by patients with schizophrenia. N Engl J Med. 1994;331:650-5.

28. Centers for Disease Control and Prevention. National Arthritis Action Plan: A Public Health Strategy. Available at: http://www.cdc.gov/nccdphp/naap.pdf. Accessed May 3, 2001.

7.

29. Burke TA, Zabinski RA, Pettitt D, et al. A framework for evaluating the clinical consequences of initial therapy with NSAIDs, NSAIDs plus gastroprotective agents, or celecoxib in the treatment of arthritis. Pharmacoeconomics. 2001;19(Suppl 1):33-47.

9. McCarthy R. Major managed pharmacy issues: Cost, cost copays? Drug Benefit Trends. 1998;10(9):22. 10. Talley CR. Medication formularies in integrated systems. Am J Health-Syst Pharm. 1996;53:261. 11. Harris Interactive. Prescription Drugs Improve Workplace Productivity, Harris Interactive Survey Says, Press Release, January 15, 2001, New York. 12. DiMasi JA. Price Trends for Prescription Pharmaceuticals. Washington, DC. U.S. Department of Health and Human Services Conference on Pharmaceutical Pricing Practices, Utilization and Costs; 2000. Background Report. 13. Elliott WJ, Weir DR. Comparative cost-effectiveness of HMG-CoA reductase inhibitors in secondary prevention of acute myocardial infarction. Am J Health-Syst Pharm. 1999;56(17):1726-32.

32. Homer CJ. Asthma disease management. New Engl J Med. 1997;227(20):1461-3. 33. Weiss KB, Gergen PJ, Hodgson TA. An economic evaluation of asthma in the United States. New Engl J Med. 1992;326:862-6.

35. Donahue JG, Weiss ST, Livingston JM, et al. Inhaled steroids and the risk of hospitalization for asthma. JAMA. 1997;277:887-91.

15. Hilleman DE, Phillips JO, Mohiuddin SM, et al. A populationbased treat-to-target pharmacoeconomic analysis of HMG-CoA reductase inhibitors in hypercholesterolemia. Clin Ther. 1999;21(3):536-62.

36. Suissa S, Ernst P Benayoun S, et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. New Engl J Med. 2000;343:332-6.

16. Noncompliance with Medications: An Economic Tragedy With Important Implications for Health Care Reform. Baltimore, MD: Task Force for Compliance; April, 1994. Report. 17. Cohen K, Vogt E, Naughton D, et al. Equating health and productivity. Business & Health. 1997; September:23-6.

19. Rizzo JA, Abbott TA, Pashko S. Labour productivity effects of prescribed medicines for chronically ill workers. Health Economics. 1996;5:249-65.

31. Asthma surveillance programs in public health departments— United States. MMWR Morb Mortal Wkly Rep.1996;45:802-4.

34. Smith DH, Malone DC, Lawson KA, et al. A national estimate of the economic costs of asthma. Am J Respir Crit Care Med. 1997;156:787-93.

14. Elliott WJ, Weir DR. Cost of cerivastatin in cost-effectiveness study. Am J Health-Syst Pharm. 2000;57(18):1713.

18. Lichtenberg F. Are the benefits of newer drugs worth their costs? Evidence from the 1996 MEPS. Health Affairs. 2001;20:241-51.

30. Health Care & Productivity. Monograph. Reston, VA. National Pharmaceutical Council; 2000.

37. Balkrishnan R, Norwood GJ, Anderson A. Outcomes and cost benefits associated with the introduction of inhaled corticosteroids therapy in a Medicaid population of asthmatic patients. Clin Ther. 1998;2:567-80. 38. Ozminkowski RJ, Wang S, Marder WD, et al. Cost implications for the use of inhaled anti-inflammatory medications in the treatment of asthma. Pharmacoeconomics. 2000;18(3):253-64. 39. Centers for Disease Control and Prevention. Office of Communication. Media Relations. Fact Sheets. Diabetes. Available at: http://www.cdc.gov/od/oc/media/fact/diabetes.htm. Accessed May 8, 2001.

| 22 |

40. Centers for Disease Control and Prevention. National Center for Chronic Disease Prevention and Health Promotion. Chronic Disease Prevention. Diabetes. Available at: http://www.cdc.gov/nccdphp/diabetes.htm. Accessed May 8, 2001.

58. Centers for Disease Control and Prevention. National Center for Chronic Disease Prevention and Health Promotion. Cardiovascular Health. About Cardiovascular Disease. Available at: http://www.cdc.gov/nccdphp/cvd/aboutcardio.htm. Accessed May 15, 2001.

41. Centers for Disease Control and Prevention. National Center for Chronic Disease Prevention and Health Promotion. Diabetes Public Health Resource. Publications and Products. National Diabetes Fact Sheet. Available at: http://www.cdc.gov/diabetes/pubs/facts98.htm. Accessed May 8, 2001.

59. Guico-Pabia CJ, Murray JF, Teutsch SM, et al. Indirect costs of ischemic heart disease to employers. Am J Manag Care. 2001;7(1):27-34.

42. Ng YC, Jacobs P, Johnson JA. Productivity losses associated with diabetes in the US. Diabetes Care. 2001;24(2):257-61.

60. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) The CONSENSUS Trial Study Group. N Engl J Med. 1987;316(23):142-5.

43. Testa MA, Simonson DC. Health economic benefits and quality of life during glycemic control in patients with type 2 diabetes mellitus: A randomized, controlled, double-blind trial. JAMA. 1998;280(17):1490-6. 44. Inzucchi SE, Maggs DG, Spollet GR, et al. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes. N Engl J Med. 1998;338(13):908-9. 45. Foster RH, Plosker GL. Glipizide. A review of the pharmacoeconomic implications of the extended-release formulation in type 2 diabetes mellitus. Pharmacoeconomics. 2000;18(3):289-306. 46. National Institute of Mental Health. The Invisible Disease: Depression. Available at: http://www.nimh.nih.gov/publicat/invisible.cfm. Accessed May 11, 2001. 47. Conti DJ, Burton WN. The economic impact of depression in a workplace. J Occup Med. 1994;36(9):983-8. 48. Goetzel RZ, Anderson DR, Whitmer RW, et al. The relationship between modifiable health risks and health care expenditures: an analysis of the multi-employer HERO health risk and cost database. J Occup Environ Med. 1998;40:843-54.

62. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334(21):1349-55. 63. Doughty RN, Rodgers A, Sharpe N, et al. Effects of beta-blocker therapy on mortality in patients with heart failure. Systematic overview of randomized controlled trials. Eur Heart J. 1997;18(4):560-5. 64. Packer M. et al, Presentation at the 22nd Annual Congress of the European Society of Cardiology, Amsterdam (August 26-30, 2000). 65. American Society of Hypertension. Understanding Hypertension. Available at: http://www.ashus.org/downloads/PatientBrochure.pdf. Accessed May 22, 2001. 66. Planlinx. Available at: http://www.planlinx.com/research_hypertension.htm. Accessed May 30, 2001. 67. Kiiskinen U, Vartiainen E, Puska P, et al. Long-term cost and lifeexpectancy consequences of hypertension. J Hypertens. 1998;16(8):1103-12.

49. Greenberg PE, Stiglin LE, Finkelstein SN, et al. The economic burden of depression in 1990. J Clin Psychiatry. 1993;54(11):425-6. 50. Kessler RC, Frank RG. The impact of psychiatric disorders on work loss days. Psychol Med. 1997;27(4):861-73.

68. Giles TD. Pharmacoeconomic issues in antihypertensive therapy. Am J Cardiol. 1999;84(2A):25K-28K.

51. Crown Wh, Hylan TR, Meneades L, et al. Tricyclic antidepressant and selective serotonin reuptake inhibitors antidepressant selection and health care costs in the naturalistic setting: a multivariate analysis. J Affect Disord. 1998;47:71-9.

69. 2001 Heart and Stroke Statistical Update. American Heart Association. Available at: www.americanheart.org/statistics/index.html. Accessed August 23, 2001.

52. Berndt ER, Finkelstein SN, Greenberg PE, et al. Workplace performance effects from chronic depression and its treatment. J Health Econ. 1998;17(5):511-35.

70. The Health Status of the United States Workforce. Pfizer Inc. 1999. Based on extrapolation of data in National Center for Health Statistics. National Health and Nutrition Examination Survey (III). 1994 Data collected 1988-1991. Data on file.

53. Finkelstein SN, Berndt ER, Greenberg PE. Improvement in subjective work performance after treatment of chronic depression: some preliminary results. Chronic Depression Study Group. Psychopharmacol Bull. 1996;32(1):33-40.

71. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998;279(20):1615-22.

54. Simon GE, VonKorff M, Heiligenstein JH. Initial antidepressant choice in primary care: effectiveness and cost of fluoxetine vs tricyclic antidepressants. JAMA. 1996;275:1897-1902. 55. Dunn RL, Donoghue JM, Ozminkowski RJ, Hylan TR. Selective serotonin reuptake inhibitor antidepressant prescribing in primary care in the United Kingdom: a longitudinal analysis. Primary Care Psychiatry. 1998;4:141-8. 56. National Heart Blood and Lung Institute. Facts About Heart Failure. Available at: http://www.nhlbi.nih.gov/health/public/heart/other/hrtfail.htm. Accessed May 15, 2001. 57. Weinberger HD. Diagnosis and treatment of heart failure. Hospital Practice. 1999. Available at: http://www.hosppract.com/issues/1999/03/weinb.htm. Accessed May 30, 2001.

61. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med. 1991;325(5):351-3.

72. Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. JAMA. 1997;278:313-21. 73. Hoerger TJ, Bala MV, Bray JW, et al. Treatment patterns and distribution of low-density lipoprotein cholesterol levels in treatmenteligible United States adults. Am J Cardiol. 1998;82:6105. 74. Roberts WC. The underused miracle drugs: the statin drugs are to atherosclerosis what penicillin was to infectious disease. Am J Cardiol. 1996;78:377-8. 75. Migraine Awareness Group: A National Understanding for Migraineurs. Migraines: Myth & Reality. Available at: http://www.migraines.org/ myth/mythreal.htm. Accessed May 25, 2001.

| 23 |

91. Sridhar S, Huang J, O’Brien BJ, Hunt RH. Clinical economics review: cost-effectiveness of treatment alternatives for gastroesophageal reflux disease. Aliment Pharmacol Ther. 1996;10(6):865-73.

76. Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999;159(8):813-8. 77. Von Korff M, Stewart WF, Simon DJ, et al. Migraine and reduced work performance: a population-based diary study. Neurology. 1998;50(6):1741-5. 78. JAMA Migraine Information Center. Newsline. Highlights of AAN 51st Annual Meeting. Available at: http://www.amaassn.org/special/migraine/newsline/conferen/aan99/0422su ma.htm. Accessed May 25, 2001. 79. Schulman EA, Cady RK, Henry D, et al. Effectiveness of sumatriptan in reducing productivity loss due to migraine: results of a randomized, double-blind, placebo-controlled clinical trial. Mayo Clinic Proceedings. 2000;75:782-9.

93. Sullivan S. Making Employee Health and Productivity the Ultimate Outcomes for Employers. Measuring the Impact of Improved Health Outcomes of Productivity. Tampa, FL; University of Kentucky Continuing Education Program: April 18, 2001. 94. Bernard S, Bernard M, Donnica L. Live long and prosper with disease management. Managed Healthcare. 1997;7(1):42-4. 95. Coons SJ. Disease management: Definitions and explorations of issues. Clin Ther. 1996;18(6):1321-6.

80. Dasbach EJ, Carides GW, Gerth WC, et al. Work and productivity loss in the rizatriptan multiple attack study. Cephalalgia. 2000;20(9):830-4. 81. Centers for Disease Control and Prevention. Division of Bacterial and Mycotic Diseases. Helicobacter pylori and Peptic Ulcer Disease. Economics of peptic ulcer disease and H. pylori infection: October 1998. Available at: http://www.cdc.gov/ulcer/economic.htm. Accessed May 28, 2001. 82. Centers for Disease Control and Prevention. Division of Bacterial and Mycotic Diseases. Helicobacter pylori and Peptic Ulcer Disease. Available at: http://www.cdc.gov/ulcer/md.htm. Accessed May 28, 2001. 83. Levin TR, Schmittdiel JA, Henning JM, et al. A cost analysis of a Helicobacter pylori eradication strategy in a large health maintenance organization. Am J Gastroenterol. 1998;93(5):743-7. 84. Gastroesophageal reflux disease (hiatal hernia and heartburn). NIH Publication No. 94-882. (1994. updated 2000). Available at http://www.niddk.nih.gov/health/digest/pubs/heartbrn/heartbrn.htm. Accessed August 24, 2001. 85. Levin TR, Schmittdiel JA, Kunz K, et al. Costs of acid-related disorders to a health maintenance organization. Am J Med. 1997;103(6):520-8. 86. Freston JW, Malagelada JR, Petersen H, McCloy RF. Critical issues in the management of gastroesophageal reflux disease. Eur J Gastroenterol Hepatol. 1995;7:577-86. 87. Bardhan KD. The role of proton pump inhibitors in the treatment of gastro-esophageal reflux disease. Aliment Pharmcol Ther. 1995;9(suppl 1):15-25.

96. Rossiter LF, Whitehurst-Cook MY, Small RE, et al. The impact of disease management on outcomes and cost of care: A study of low-income asthma patients. Inquiry. 2000;37(2):188-202. 97. Disease Management: Balancing Cost and Quality: An Annotated Bibliography of Studies on the Benefits of Disease Management Services for the Treatment of Asthma. Reston, VA. National Pharmaceutical Council, Inc; 1999. 98. Disease Management: Balancing Cost and Quality: An Annotated Bibliography of Studies on the Benefits of Disease Management Services for the Treatment of Congestive Heart Failure. Reston, VA. National Pharmaceutical Council, Inc; 2000. 99. Hershberger RE, Ni H, Nauman DJ, et al. Prospective evaluation of an outpatient heart failure management program. J Card Fail. 2001 7(1):64-72. 100.Disease Management: Balancing Cost and Quality: An Annotated Bibliography of Studies on the Benefits of Disease Management Services for the Treatment of Diabetes. Reston, VA. National Pharmaceutical Council, Inc; 2000. 101.Marshall CL, Bluestein M, Briere E, et al. Improving outpatient diabetes management through a collaboration of six competing, capitated Medicare managed care plans. Am J Med Qual. 2000;15(3):65-71. 102.Big Savings With CHF DM Programme. PharmacoEconomics and Outcomes News. 2000; 289:9. Available at: http://www.pharma.org/updates//2001-08-22.287.phtml. Accessed August 30, 2001. 103. National Committee for Quality Assurance. The business case for health care quality. State of Managed Care Quality, 2001. Available at: http://www.ncqa.org/somc2001/biz_case/somc_2001_biz_ca se.html. Accessed September 16, 2001.

88. Harris RA, Kupperman M, Richter JE. Proton pump inhibitors or histamine-2 receptor antagonists for the prevention of recurrences of erosive reflux esophagitis: a cost-effectiveness analysis. Am J Gastroenterol. 1977;12:2179-87. 89. Holzer SS, Juday TR, Joelsson B, Crawley JA. Determining the cost of gastroesophageal reflux disease: a decision analytic model. Am J Manag Care. 1998;4;1450-60. 90. Skoutakis VA, Joe RH, Hara DS. Comparative role of omeprazole in the treatment of gastro-esohageal reflux disease. Ann Pharmacother. 1995;12:1252-62.

92. Gerson LB, Robbins AS, Garber A, Hornberger J, Triadafilopoulos G. A cost-effectiveness analysis of prescribing strategies in the management of gastroesophageal reflux disease. Am J Gastroenterol 2000,95(2):395-407.

104. National Committee for Quality Assurance. NCQA Releases State of Managed Care Quality: 2001 report; second straight year of substantial gains recorded [press release]. September 6, 2001. Available at: http://www.ncqa.org/communications/news/index.htm. Accessed September 16, 2001.

| 24 |

National Pharmaceutical Council 1894 Preston White Drive Reston, VA 20191 www.npcnow.org