Influencers of Generic Drug Utilization: A Systematic Review

Abstract

Introduction

With an increase in prescription drug spending and rising drug costs there is a need to encourage the use of generic prescription drugs. However, maximizing generic drug use is not possible without the public’s positive perception and meeting their informational needs about generic drugs. Thus, improving the public’s confidence in, and knowledge of generic drugs on the market is critical. The objective of this systematic review is to examine and evaluate the studies focusing on the nature and extent of key factors influencing generic drug use in the United States in order to help guide policy, education and practice interventions.

Materials and methods

Using multiple search engines and key word screening criteria, empirical studies published in English between January 1, 2005 and December 31, 2015 were identified. A qualitative synthesis of the evidence identified domains of key factors that influenced generic drug use across studies.

Results

Over 3,000 citations met the key word screening criteria; 67 of these met inclusion criteria for the systematic review. Seven domains of factors that influence generic drug utilization were identified: 1) patient-related factors, 2) formulary management or cost containment, 3) healthcare policies, 4) promotional activities, 5) educational initiatives, 6) technology, and 7) physician-related factors.

Conclusion

Patients, physicians, pharmacists, formulary managers, and policymakers play an important role in generic drug use. Understanding the factors influencing generic drug use can help guide future policy, education, and practice interventions to increase generic drug use.

Introduction

On July 9, 2012, Generic Drug User Fee Amendments of 2012 (GDUFA) (Public Law 112–144, Title III) were enacted to provide timely access to safe, high-quality, and affordable generic drugs.¹ Generic drug policies such as GDUFA can make a significant contribution to increasing the availability of affordable prescription drugs. However, maximizing the use of generic drugs is not possible without the public’s positive perception and meeting their informational needs about generic drugs.

Generic drugs in the United States accounted for 89 percent of total prescription drugs filled, yet only 27 percent of total prescription costs in 2016.² At the national policy level, generic substitution is recognized as an important and effective tool to control rising prescription drug costs. In the past 10 years, the rate of increase in drug spending has declined, with generic drug use contributing to the declining rate of drug spending.³ Generic drugs have played a key role in further slowing U.S. health care spending, by reducing Medicare spending by $67.6 billion and Medicaid spending by $32.7 billion in 2015.²

While the important role generic drugs play in cost containment and patient outcomes is known and that there are multiple factors that may influence generic drug use, no prior work has systematically assessed the key influencers of generic drug substitutability. The objective of this systematic review was to examine and evaluate the studies focusing on the nature and extent of key factors influencing generic drug use in the United States. Understanding these factors can help to guide policy, education and practice interventions.

Material and Methods

Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines^{4, 5} were used to guide the systematic review. Using multiple search engines, empirical studies published in English between January 1, 2005 and December 31, 2015 were identified. The search engines PubMed, Web of Science, OVID-Medline, Google Scholar, EBSCO-International Pharmaceutical Abstracts (IPA) and EBSCO-Medline were utilized to identify relevant studies (Table 1). A search strategy was finalized for each search engine before conducting the search between February and April, 2016.

Table 1.

General MeSH^® Search Terms

Search Domain	Search Engine
	PubMed	Web of Science	OVID-Medline	Google Scholar	EBSCO- IPA & Medline
Generic	Generic Drugs	Drug Industry, Drug Manufacturer Drug, Generic, Nonproprietary	Drug, Generic	Generic drug	Generic, Nonproprietary
Policy	Policy/policy makers	Health maintenance organization, Medicare part D Policy, Health policy	Health Policy Health Maintenance organizations, Medicare Part D	Health policy
Education	Professional Education	Education, Patient, Patient handout, Graduate education, Continuing education, Nursing education	Education, Graduate education, Nursing education Health education, Patient education handout	Professional education
Utilization	Drug utilization	Drug utilization	Drug utilization	Generic drug utilization	Generic utilization
Health Behavior/Attitude	Health Behavior	Health behavior, Health knowledge, Health attitudes	Health knowledge, attitudes, practice	Health behavior Influence, Impact, Attitude, Perception
Formularies	Formularies	Formularies, Hospital formularies, Pharmacopoeias		Formularies
Health Benefits	Health Benefit Plans	Employee health benefit plan	Health benefit plans, Employee/health
Manufacturers	Manufacturers
Influence	Influence concept	Influence, Affect, Effect	Influence		Influence, Affect, Effect

MeSH^® (Medical Subject Headings) is a set of terms naming descriptors in a hierarchical structure that enables searching at various levels of specificity.

IPA: International Pharmaceutical Abstracts

Search terms and parameters were adjusted for each database while maintaining a common overall framework. Due to the differences in output styles, search results from each database were handled separately. The abstracts of the articles identified through search terms were imported using EndNote^® reference management software. The abstracts were then screened for duplicates.

Study Selection

The abstracts of the articles that were identified using key words listed were assessed independently by two reviewers. Any disagreements were resolved by discussion among reviewers and input from a third reviewer. Abstracts that were duplicates, not written in English, published prior to 2005, not empirical, or were not policy or methodologically relevant to generic drug use or influence were excluded. If the title and abstract provided insufficient information to assess the inclusion criteria, a full text review was conducted.

Three hundred and seven articles were selected for full text review based on the title and abstract review. Articles were further excluded if not focused on US policy, if not methodologically (i.e., empirical and original research) or otherwise topic relevant, or risk of bias was present. Risk of bias was primarily assessed through the utilization of assessment criteria of what was reported against what was conducted in each of the studies. Each aspect of each study’s methods was assessed as either done well, or done poorly, and if they were fully reported, ambiguously or incompletely reported, or not reported. The information reported in the methods was then compared to what was reported in the results and discussion sections of each study. Studies that the review team deemed as “biased” due to study design or reporting of findings were excluded from the systematic review to reduce bias across studies. For example, we excluded studies if the methods and findings were inconsistent and thus may have introduced bias.

Data Collection

The research team then independently abstracted data from the selected studies. The abstracted data included study objective(s), design, population studied, data source(s), exposure, outcomes, and study results. Studies were also reviewed for presence of any bias. These data were collected in an extraction sheet developed by the review team, comprised of abstract review determinations, and data abstracted from full study reviews. Disagreements regarding inclusion or exclusion criteria or data abstraction were resolved by discussion with all team members until consensus was reached.

Data Analysis

A qualitative synthesis of the evidence identified domains of key factors that influenced generic drug use across studies. The factors identified were grouped by “domain” to allow for broad discussion of factors.

Results

The systematic search of the literature identified 3,263 articles meeting the key word screening criteria. After removing duplicates, 1501 articles remained. After two reviewers reviewed the abstracts using the methodology described above, there were 307 articles meeting the inclusion criteria for in-depth review. The full-text review of the 307 articles resulted in excluding 239 articles, therefore leaving 67 articles included in the systematic review. Articles were excluded due to publication type (65)¹, country of policy of focus (106)², study methods (6)³, topic relevancy (62)⁴, and publication date (2)⁵. All five articles removed due to “study methods” were systematic or literature reviews, therefore making them secondary sources. All articles included in the systematic review were empirical studies that included original research. The information reported in the methods of the remaining articles was then compared to what was reported in the results and discussion sections of each study for possible further exclusion. No additional articles were excluded due to a biased study design or reporting of findings. Figure 1 provides a summary of the findings after applying the inclusion/exclusion criteria to both the abstracts and full-text articles.

Figure 1.

Literature Retrieval Flowchart

Factors discussed in the 67 articles included in the systematic review are presented below by domain and include the following domains: patient-related; formulary management and cost containment; Medicare and Medicaid policies; promotional activities; educational initiatives; technological; and physician-related. The results are presented in descending order by the number of articles discussing factors associated with each domain and does not represent the relative impact of each domain.

Patient-Related Factors

Of the 67 articles included in the systematic review, 21 indicated that patient-related factors influence generic drug use. These studies show that sociodemographic factors (e.g., race, sex, age, and income), health status, insurance type or coverage, patient knowledge, prior experience with generics, or communication with their physician are consumer-driven influencers of generic drug use. More specifically, Caucasian patients were less likely than African American patients to utilize generic antidepressant drugs and use a higher share of older drugs.⁶ Another study found that African Americans and Asian/Pacific Islanders were more likely to rate generics as of greater value when compared to Caucasians.⁷ However, as suggested in several studies, non-Caucasian patients were more likely than Caucasian patients to have negative beliefs in the equivalence and effectiveness of generics.^8–10 Several studies suggest that these differences in generic drug utilization by race and ethnicity may be influenced by other factors such as insurance coverage or other patient-related factors.^{6, 10–12}

Income was another patient-related factor that influences generic drug use. Patients with high annual incomes, above $100,000, were more likely to take a generic alternative when compared to patients with incomes below $30,000.⁷ Additionally, Yun et al. ¹³ found that Medicare beneficiaries living in high income areas (annual income ≥ $75,000), who were receiving a low-income subsidy were less likely to switch from branded Fosamax^® plus vitamin D to a generic alternative. Another study found that patients earning between $20,000 and $30,000 were more likely to use a generic drug discount programs when compared to patients with incomes of or below $10,000.¹⁴

Many of the studies in the systematic review covered additional patient factors such as healthcare coverage, the number of prescription medications, patient knowledge, patient drug history, and patient/physician communication. Patients without health insurance were shown to be more likely to utilize generic drugs or generic drug discount programs.¹⁵ One study found that uninsured patients were more likely than privately insured patients to have a generic drug dispensed.¹⁶ Additionally, patients with more filled prescriptions were more likely to use generic drug discount programs.¹⁷ Li and colleagues¹⁸ suggest that a lack of patient knowledge may explain a decrease in brand-name prescriptions that was not offset by an increase in generic prescriptions among Medicare beneficiaries. Shrank and colleagues¹⁹ found that patients who were initially prescribed a generic drug were less likely to switch to a drug from another tier when compared to patients initially prescribed a non-preferred medication. Communication was also shown to be a key factor, with a lack of communication between patients and healthcare providers contributing negatively to views and utilization of generic drugs. ^{9, 20} In addition, Shrank et al., ²¹ show that patients who communicated with their physician about generic drug use were more likely to fill a generic medication than patients who did not communicate.

While several articles suggested that individuals with lower income, or whom are Caucasian, male, or younger are less likely to use a generic drug, there were several studies where these results were not consistent. For example, a study conducted by Hulbert et al. 27 showed that those with an annual income below $30,000 had more positive beliefs in the effectiveness of generic drugs compared to those with annual incomes above $30,000. Likewise, Gagne et al., ²² Keenum et al.,²³ Mager et al.,²⁴ Shrank et al.,^{7, 25} and Zhang et al.²⁶ show that there may be variation in the relationship between patients’ age and sex and their generic drug use and perceptions.

Formulary Management and Cost Control Factors

Fourteen articles described formulary management and cost control factors that influence generic drug use. The majority of these articles examined the effects generic drug costs, copayments, and shifts in formularies have on overall generic drug use. An increase in drug costs and shift to more costly 3-tier formularies from 2-tier or other formulary designs results in a decline in brand drug utilization and increase in generic drug use.²⁷ Likewise, as consumer out-of-pocket costs for brand-name drugs increase, so does generic drug use.²⁸

More specifically, studies point to the influence drug copays have on generic drug use, with generic drug use increasing as generic drug copayments decrease,^{25, 27, 29} or brand copays increase.^{30, 31} However, Sen et al., ³² observed that although copays were higher for brand-name drugs, the switch to generic drugs among CHIP enrollees was unclear. Additionally, Rodin et al., ³³ found that lowering generic drug copays and raising brand-name drug copays did not lead to a complete shift to generic drugs among patients with particular conditions.

Generic drug use was also shown to decrease with an increase in copayments for drug equivalents.³⁴ Other studies found these results to vary, with one study showing that high deductible health plans do not significantly increase generic drug use, except in the case of antidepressants.³⁵ Additionally Tang et al.³⁶ found that enrollees in plans with higher average generic cost-sharing strategies were less likely to use generic alternatives to antidepressants, antidiabetics, and statins compared to those in plans with lower cost-sharing strategies. Similar cost-sharing strategy might influence generic drug use differently by health plans, for example, the formularies of Health Maintenance Organization (HMO) plans were shown to have a greater impact on plan enrollees’ generic drug substitution habits than the habits of self-insured enrollees.³⁷ Another type of health plan, a Consumer-Driven Health Plan (CDHP), with a three-tier pharmacy benefit design showed a reduction in generic drug use.³⁸ Lastly, a study conducted by Dai and colleagues ³⁹ found that overall, plan bids (i.e., expected costs of providing benefits to the typical beneficiary) were lower when enrollee cost sharing was higher, which may reflect the likely use for brand name drugs in plans with lower bids. The authors concluded that insurers expect that by increasing the cost sharing amount for brand drugs, enrollees would be more likely to use generic drugs.

Medicare, Medicaid, and State-specific Generic Drug Substitution Policies

Results show that the policy influencers on drug use are multifaceted and range from Medicare Part D and Medicaid coverage to state-specific generic drug substitution policies. Ten articles examined the specific role of the Medicare Part D coverage gap on generic drug use, the role Medicare Part D has on state Medicaid programs, and the impact of policies reducing Medicaid reimbursement rates. Results from the systematic review show that Medicare beneficiaries are more inclined to utilize generic drugs while in the Medicare Part D coverage gap.^40–42 However, the Part D coverage gap is also associated with fewer monthly prescriptions and a higher likelihood of non-adherence for specific drugs among patients with no coverage gap or generic only coverage.¹⁸ Additionally, Goedken et al., ⁴³ found that generic drug use was higher among beneficiaries with Part D coverage than Medicare beneficiaries with employer-sponsored drug coverage, and that generic drug use among Part D beneficiaries did not significantly differ from Medicare beneficiaries with no drug coverage. Zhang et al., ⁴⁴ found that generic drug use was overall lower for Part D enrollees than for comparable non-enrollees. However, this association depended on the particular drug. For example, Part D enrollees had higher generic use of benzodiazepines and ace inhibitors compared to non-enrollees.

More recent efforts to encourage generic drug use among Medicaid beneficiaries have had a modest positive impact on generic drug use.⁴⁵ Other Medicaid efforts including lower cost sharing for generics, mandatory generic substitution, step therapy, preferred drug lists, and brand dispensing limits without approval from the Medicaid agency have also been shown to have impact on generic drug use.⁴⁶ More specifically, Shrank et al., ⁴⁷ found that state Medicaid programs could reduce costs if all states adapted generic substitution policies that do not require patient consent. Alpert et al.⁴⁸ found that a Medicaid policy instituted in 2000, which reduced reimbursement rates to pharmacies for select generic drug products, did not lead to an increase in pharmacy purchasing cheaper generic drug alternatives over more expensive equivalent drug products.

Promotional Activities

Eleven articles examined the influence of promotional activities on generic drug use. Many of these articles focused on the use of samples provided by pharmaceutical companies as marketing strategies for brand and higher cost drugs. These studies show that these promotional activities are effective in increasing brand and higher cost drug use and decreasing generic drug use by influencing physician prescribing patterns. ^15,49–53 In addition, one study found that interactions between pharmaceutical companies and physicians increased the likelihood of brand name drug prescribing rates. ⁵⁴ Contrary to the focus of the influence promotional activities have on brand drug prescribing, one study examined the ease of accessibility to generic drugs in a kiosk and the positive influence it had in generic antibiotic rates and costs.⁵⁵ Another study that examined the influence of specific interventions on generic drug use showed that the imagery and narration styles of advertising materials did not appear to influence patients’ perceived “informativeness”, intent to seek information on generic drugs, their intent to switch to a generic drug.⁵⁶ Additionally, generic drug advertising campaigns did not appear to have an overall influence on generic drug use.⁵⁷ However, a 2013 study by Nemlekar et al., ⁵⁸ found that incentive programs such as prescription drug coupons and vouchers encouraged non-preferred brand name drug use over preferred brand name drug use. Similarly, this study also found that patients are more likely to shift from generic to brand name drugs when they receive copay subsidy coupons.

Educational Initiatives

Four articles focused on the role of educational initiatives on generic drug use. These articles show that educational activities related to evidence-based information on generic drugs as part of medical training, educational meetings, and systems supports for healthcare professionals positively influences generic drug use.^50,59,60 Educational initiatives targeted at patients also appear to have a positive influence on generic drug use, with studies showing that educational initiatives and outreach encourage patients to switch from brand name drugs to generic and develop less favorable attitudes towards brand name drug manufacturers.⁶¹

Technology

Results from 6 of the studies reviewed show that technology plays a role in generic drug use. Two studies reviewed show that e-prescribing increased the likelihood of generic drug prescribing.^62,63 However, one study found that generic drug prescribing patterns were similar between e-prescribers and traditional prescribers, with both groups appearing to have high levels of formulary compliance.⁶⁴ Scott et al. ⁶⁵ found that physician practices participating in an automated generic drug sampling program through a generic drug vendor saw an increase in the average generic drug rate. Additionally, Dobscha et al. ⁵⁹ found that system supports, such as revised electronic order menus which identified the new preferred agent, positively contributed to generic drug use. One study found that Wikipedia is the top internet information source for those searching for information related to generic drugs and it often has inaccurate information on generic medications which may mislead patients’ understanding of generic drugs.⁶⁶

Physician-Related Factors

In addition to the 6 domains identified in this review, there were several factors that did not fit into any of the identified domains that had an influence on generic drug use. Specialists were shown to be more likely than general practitioners to prescribe brand name or higher cost drugs.⁶⁷ Other studies examined show that the prescribing patterns of attending physicians influenced the prescribing patterns of resident physicians.⁶⁸ Similarly, the resident’s experience level appears to influence generic drug use, with new residents more likely to use generic names compared to those more experienced residents.⁶⁹ Location of residency plays a role in generic drug use, suggesting that practice culture impacts a residents’ prescribing patterns. ⁶⁸ In addition, physicians belonging to an HMO are no more likely to prescribe generic drugs when compared to doctors belonging to other insurance models.⁷⁰ Physician influence was identified as a factor of generic drug dispensing among pharmacists; Devine et al., ⁷¹ found that having a clinical pharmacist employed in physician group practice increased the dispensing of generic drugs. Shrank et al.⁷² found that the age of physicians also influences generic drug use, with older physicians less likely than younger physicians to take generic drugs themselves or recommend or prescribe generic drugs due to unfavorable perceptions of generic drugs. One study found that a lack of generic versions of a particular brand-name drug exists and negatively affects generic drug use.¹⁸ Table 2 summarizes the findings across the seven domains.

Table 2.

Factors Associated with Generic Drug Use

Area	Factors Influencing Generic Drug Use	Example
Patient-Related	Race/Ethnicity Sex Age Income Health status Insurance type or coverage Prior experience with generic drug use	Whites less likely than Blacks or Hispanics to utilize generic drugs Women more likely to use generic drugs than men Older patients have higher generic drugs use compared to younger patients Higher income [> 100,000] associated with greater generic drugs use Patients with greater burden of comorbidity have greater generic drugs initiation Uninsured patients more likely to use generic drugs Patients with prior use of any generic are more likely to use generic drugs
Formulary Management and Cost Controls	Effects of generic drug costs Copayments Shift in formularies	As drug costs increase generic drugs use increases Increase in brand-name copays = increase in generic filled prescriptions Shift to more costly 3-tier formularies from 2-tier or other formularies leads to a decrease in brand drug use & an increase generic drugs use
Medicare, Medicaid, and State-specific Generic Drug Substitution Policies	Medicare Part D coverage gap Medicaid coverage State-specific generic drug substitution policies	Medicare beneficiaries are more likely to use generic drugs while in the coverage gap Preferred drug lists for Medicaid beneficiaries leads to increase in generic drugs use Laws that require consent prior to generic substitution reduce the use of generics
Promotional Activities	Use of sample drugs provided by pharmaceutical companies as marketing strategies for brand and higher cost drugs Interactions between pharmaceutical companies and physicians Generic drug kiosks Drug advertising	Greater brand-name drug samples = greater brand-name drug use & lower generic drug use More interactions between pharmaceutical companies and physicians increases the likelihood of prescribing brand-name drugs Generic drug kiosk increases the influence on accessibility and generic antibiotic use rate Imagery and narration styles of advertising materials did not appear to influence patients’ perceived “informativeness,” intent to seek information on generic drugs, or their intent to switch to a generic
Educational Initiatives	Educational activities related to evidence-based information on generic drugs as part of medical training Educational meetings	Trainings lead to increase of generic drugs use Positive effect on patients view of generics
Technology	E-prescribing Internet searches for generic medications Automated generic drug sampling through a generic drug vendor Systems supports for healthcare professionals	E-prescribing led to greater generic drug prescribing patterns Top internet search, Wikipedia; providing consumers with poor information on generics Automated generic drug sampling increased generic drug use Electronic order menus lead to an increase in generic prescribing among VA physicians
Physician-Related Factors	Physician specialty Age of physician Resident’s experience level Location of the residency and clinical practice culture	Specialists have higher likelihood of prescribing brand-name drugs Greater the age of physician the less likely to take generics or recommend them Newer the resident the more likely to use generics Large influence on physician’s prescribing patterns

Discussion

Although generic drug use has increased over the past decade, their use varies across drug classes and categories. For example, generics have been widely used among some therapeutic classes such as antihypertensives,⁷³ antidepressants,^{74, 75} antidiabetics, statins, and antibiotics,⁷⁶ while generics are not widely used among sterile injectables,⁷⁷ specialty drugs,⁷⁸ atypical antipsychotics,⁷⁹ and drugs with a narrow therapeutic index (NTI) such as antiepileptics, thyroid drugs, and immunosuppressant drugs.⁸⁰ Additionally, generic drug use varies across different populations affected by prescription formularies and policies. Among Medicare beneficiaries, generic drug use, and the savings realized, also varies across therapeutic classes. One study found that when compared to patients with diabetes whose healthcare coverage is provided through the U.S. Department of Veterans Affairs (VA), Medicare beneficiaries with diabetes were more than twice as likely to use brand-name drugs; if Medicare beneficiaries were to utilize generic drugs at the same rates as VA patients, then Medicare could save more than $1 billion per year.⁸¹

Generic drug use may be greatly affected by some key groups’ behaviors and perceptions toward generic drugs. There is debate within the healthcare community regarding the appropriateness of generic drug substitution. Some drug safety experts have argued that the FDA’s bioequivalence standards are inadequate, especially for drugs with an NTI. For example, small pharmacokinetic parameter differences between generic and brand carbamazepine products may lead to differences in seizure control or adverse effects in patients with epilepsy.⁸² Generic antidepressants offer significant cost savings compared with brand-name antidepressants, but critics of managed care interventions promoting generic medication use suggest that some generic antidepressants are not as safe or effective as the brand alternatives and generic substitution could lead to reduced medication adherence or early treatment discontinuation.^83–85

In addition to healthcare professionals’ concerns and perceptions regarding the safety of generic drugs, generic drug use may be influenced by patients’ perceptions. While many patients have reported taking a generic drug, many perceive generic drugs as less effective or safe than brand name equivalents.^{86, 87} Patients’ perceptions about generic drugs may ultimately influence prescribing and dispensing patterns. According to results from a national survey of U.S. physicians with a variety of specialties, more than one-third of respondents indicated that, when requested by patients, they often or sometimes prescribed brand-name drugs when appropriate generic substitutes were available.⁸⁸ Additionally, a 2016 study suggests that while the majority of patients have positive perceptions of generic drugs, lingering negative perceptions among some may still exist, with these patients believing physicians should prescribe brand-name drugs when generic drug alternatives are available or asking that their physician prescribe a brand-name drug over a generic alternative.⁸⁹

Physician and patient behaviors and perceptions may also impact the effectiveness of generic drug substitution policies. Once the FDA approves a generic drug, prescribers and pharmacists may substitute the generic for its brand-name equivalent, according to state laws and regulations. Generic substitution, however, can be bypassed by active interventions of patients or physicians. Some states, for example, require a patient’s consent prior to a generic substitution by a pharmacist. In addition, physicians can write prescriptions for brand-name drugs that are specifically marked “dispense as written”. Physicians and patients may direct pharmacists to dispense as written,⁹⁰ or specifically request that pharmacists not fill with a generic equivalent,⁸⁹ and these actions contribute to an estimated $1.2 billion in additional drug costs annually in the U.S.⁹¹

Through a systematic review of the literature, seven key domains of factors that influence generic drug use were identified. Patient-related factors, including insurance coverage type, patient demographics, patients’ prior experience with generic drugs, and patients’ communication with healthcare providers regarding generic drugs were the most frequently discussed in the literature, suggesting that patient-related factors play a crucial role in generic drug use. Patients with lower incomes, Caucasian, male, young, or who are otherwise healthy are less likely than their counterparts to utilize generic drugs and may need additional or more targeted educational materials and information from healthcare professionals in order to increase generic drug utilization. A targeted approach may not only have a high impact on those groups identified as resistant to generic drug use, but targeted educational materials are also likely to encourage healthcare providers to communicate in a more effective and efficient manner with patients regarding generic drug use.

Formulary management or cost containment measures were shown to have the intended effect of increasing generic drug use. Many of the articles reviewed focusing on formulary management or cost containment examined the impact of cost for generics, copayments, and shift in formularies on overall generic drug use. Articles examining these various factors and outcomes were consistent in their conclusions that formulary management or cost containment measures positively influence generic drug use. More specifically, an adjustment in cost sharing mechanisms influences drug use, with decreased generic drug copayments increasing generic drug use, shifts away from two-tier or other formularies to more costly 3-tier formularies decreasing brand drug use, and Medicare Part D enrollees in plans requiring prior authorization with a greater likelihood of using generic antidepressants, antidiabetics, and statins than their counterparts in plans without a prior authorization requirement.

Like formulary management or cost containment, federal and state health insurance policies were shown to be a major factor influencing broad changes in generic drug use by encouraging generic drug use in the Medicare and Medicaid programs. Specifically, Medicare beneficiaries are more inclined to utilize generic drugs while in the Medicare Part D coverage gap when much of the cost for drug-related expenses are out-of-pocket. Results also show that many of the recent Medicaid policy changes intended to encourage generic drug use have been successful. It may also be inferred that generic substitution laws may lower drug expenditures under Medicaid. These results show that many recent policy changes have been effective in altering generic drug use patterns broadly across Medicare and Medicaid populations, but also suggest much can be learned from each of these policies.

Promotional activities by pharmaceutical companies have been shown to increase brand name drug use. Studies included in this systematic review that examined the impact of promoting generic drugs in healthcare settings showed that those activities were effective in increasing generic drug use as well.

Other ways in which generic drug use was impacted was through educational initiatives, technological advances, and physician characteristics. Evidence suggests that educational initiatives related to generic drugs should be focused on men, individuals with lower socio-economic status, and individuals belonging to a minority group. These groups were seen as less likely to take generics or have negative impressions of generic drugs and may benefit from targeted outreach. Targeted outreach or additional training may also benefit younger physicians, as they may be greatly influenced in their prescribing patterns by their use of technology (e-prescribing) and their training (attendee physicians prescribing patterns).

Limitations

This review has several limitations. The large number of publications in this review created a challenge in isolating factors in which to categorize the exposure in each of the studies or the relative effect of the exposure on generic drug use. It also proved challenging to summarize results in instances in which outcomes examined and results found varied or were multifaceted. The large number of published studies examining generic drug utilization patterns and influencers is not surprising due to the major shifts in the approval and manufacturing of generic drugs in recent years and greater awareness of cost savings associated with generic drugs. Finally, this review was unable to more closely examine possible differences between factors affecting generic drug use and generic drug discount program use or the impact of recent policy changes resulting from the Affordable Care Act (ACA) and Medicare policy shifts on generic drug use since most of the articles reviewed predated the ACA.

Strengths

One major strength is this review’s focus on the multiple factors and ways these factors influence generic drug use in the United States. While numerous international studies were identified examining this topic, empirical studies focusing on a comprehensive review of unique factors that influence generic drug use in the United States were scarce. This systematic review fills this gap in the literature. Another strength is the use of the PRISMA guidelines for the review process. A thorough and systematic search of multiple search engines was conducted and data abstraction was performed by multiple reviewers, with questions and concerns discussed until consensus was reached.

Conclusion

The intent of this systematic review was to contribute to a better understanding of the nature and extent of key factors that influence generic drug use in order to allow researchers and policymakers to best focus future research, educational and policy endeavors encouraging increased generic drug use. While results varied across the 67 peer-reviewed articles reviewed, the majority of the articles focused on 2 of 6 domains influencing generic drug use: patient-related and formulary management or cost containment. However, while a broad range of factors were discussed in the literature, the level of influence these factors have may have changed in light of recent policy shift. Future research should more closely examine the differences between generic drug use and generic drug discount program use as well as examine the effects of recent policy changes, such as the ACA and GDUFA, have had on generic drug use. Results from this and future research may be useful in the development of targeted outreach materials for each of the groups influencing generic drug use as well as other policy or programmatic initiatives intended to encourage generic drug use.

Abbreviations

ACA

Affordable Care Act

CDHP

Consumer-Driven Health Plan

CHIP

Children’s Health Insurance Program

FDA

U.S. Food and Drug Administration

GDUFA

Generic Drug User Fee Amendments

HMO

Health Maintenance Organization

IPA

International Pharmaceutical Abstracts

NTI

Narrow Therapeutic Index

MeSH^®

Medical Subject Headings

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

VA

Veterans Affairs