Active pharmaceutical management strategies of health insurance systems to improve cost-effective use of medicines in low- and middle-income countries: a systematic review of current evidence.

OBJECTIVES: Health insurance systems have great potential to improve the cost-effective use of medicines by leveraging better provider prescribing, more cost-effective use by consumers, and lower prices from industry. Despite ample evidence from high-income countries, little is known about insurance system strategies targeting medicines in low- and middle-income countries (LMIC). This paper provides a critical review of the literature on these strategies and their impacts in LMIC. METHODS: We conducted a systematic review of published peer-reviewed and grey literature and organized the insurance system strategies into four categories: medicines selection, purchasing, contracting and utilization management. RESULTS: In n=63 reviewed publications we found reasonable evidence supporting the use of insurance as an overall strategy to improve access to pharmaceuticals and outcomes in LMIC. Beyond this, most of the literature focused on provider contracting strategies to influence prescribing. There was very little evidence on medicines selection, purchasing, or utilization management strategies. CONCLUSIONS: There is a paucity of published evidence on the impact of insurance system strategies on improving the use of medicines in LMIC. The existing evidence is questionable since the majority of the published studies utilize weak study designs. This review highlights the need for well-designed studies to build an evidence base on the impact of medicines management strategies deployed by LMIC insurance programs.

Competitiveness in follow-on drug R&D: a race or imitation?

The development of 'follow on' or 'me too' drugs - generally defined as a drug with a similar chemical structure or the same mechanism of action as a drug that is already marketed - has attracted contrasting views. Some have argued that follow-on drugs often provide useful alternative or enhanced therapeutic options for particular patients or patient subpopulations, as well as introducing price competition. Others, however, consider that the development of such drugs is duplicative and that the resources needed would be better directed elsewhere. Implicit in some of this criticism is the notion that the development of me-too drugs is undertaken after a first-in-class drug has made it to market and proved commercially successful. In this Perspective, using analysis of development and patent filing histories of entrants to new drug classes in the past five decades, we provide new evidence that the development of multiple new drugs in a given class is better characterized as a race, rather than the imitation of successful products.

Off-label use reimbursement.

In this study, the authors examine factors underlying payer off-label use reimbursement policies. Updating a study published 14 years ago, presenting the results of the survey of 179 payers administering public (Medicare and Medicaid) pharmacy benefits. The focus is on payers administering pharmacy benefits in the public sector for two reasons: First, transparency; there is a tendency for such payers to reveal more about their decisionmaking processes than payers that exclusively deal with the commercial market. Second, Medicare and Medicaid set the pace in terms of specific policies on off-label use reimbursement, particularly with regard to anti-cancer agents and biologics. The authors investigate the role of primary and secondary sources governing reimbursement of unlabeled indications, including biopharmaceutical compendia, peer-reviewed literature, and clinical practice guidelines. The findings point to the continued variation of off-label use reimbursement policies across payers. Furthermore, the survey data shed light on payer efforts to design off-label use reimbursement strategies, including the use of cost-effectiveness.

Racial disparities among clinical research investigators.

Evidence shows that minority patients are underrepresented in clinical trials. The development of new drugs and treatments, however, requires that clinical research studies include representative participants, particularly in light of evidence indicating that minority populations sometimes respond differently to prescription medications. Racial disparities among clinical investigators are often cited as a major reason why minority patients are underrepresented in clinical trials. However, there is little to no empirical data to support or refute the prevalence of disparities among clinical investigators. The Tufts Center conducted two online surveys of 1376 physicians. The first survey (N = 859 respondents; 31% response rate) assessed the overall incidence of minority physician involvement in clinical research. The second survey (N = 768 respondents; 20% response rate) assessed the demographics, experience, and infrastructure of minority physicians who have participated in clinical research as a principal investigator or subinvestigator. The results of this study indicate that significant racial disparities exist among clinical investigators. The results also support assertions that physician race influences race of the clinical trial volunteer. The incidence of participation in clinical research among minority physicians is well below that observed among white physicians, more so with regard to U.S. Food & Drug Administration-regulated clinical trials funded by industry. Minority investigators tend to conduct and initiate fewer clinical trials annually. Yet minority and white physician interest in participating in clinical research is similarly high. Minority investigators tend be younger, with more limited clinical research infrastructure and support than their white counterparts. New strategies, policies, incentives, and reforms are needed to address racial disparities among clinical investigators. In addition, disparities among both volunteers and investigators need to be tracked more closely and methodically to monitor and assess the impact of newly implemented programs and reforms.

Are Medicare plans complying with CMS regulation?

OBJECTIVES: The US Centers for Medicare and Medicaid Services (CMS) have put forth guidance recommending coverage of 75% of the costs of 'all or substantially all' drugs in six therapeutic categories deemed medically necessary for Medicare beneficiaries: anticonvulsants, antidepressants, antineoplastics, antipsychotics, HIV/AIDS and immunosuppressants. For 2007 filings, we analyzed compliance by 36 leading prescription drug plans with the CMS guidance. METHODS: Using databases at the Tufts Center for the Study of Drug Development, we identified 201 drugs approved by the US FDA between 1962 and 2007 in the six therapeutic categories mentioned above. For these drugs, we gathered data from 36 prescription drug plans on prices, formulary placement, cost-sharing and conditions of reimbursement. Our primary source for formulary data was the Formulary Finder on the CMS website. RESULTS: Plans are not complying with the 'all or substantially all' guidance. Across all six categories, an average of 17% of drugs are not covered, with a higher percentage of exclusions among antineoplastics and immunosuppressants. In addition, 18% of covered drugs have one or more conditions of reimbursement, with prior authorization leading the way at 15%, even in categories in which the use of prior authorization is not sanctioned (e.g., HIV/AIDS). CONCLUSIONS: Noncompliance with CMS guidance suggests CMS oversight may be lacking. Further research must be performed to determine whether, on balance, formulary exclusions and restrictions in these categories are harmful to patient outcomes.

Patient access to pharmaceuticals: an international comparison.

We have identified eight sub-dimensions of patient access to pharmaceuticals: marketing approvals, time of marketing approval, coverage, cost sharing, conditions of reimbursement, speed from marketing approval to reimbursement, extent to which beneficiaries control choice of their drug benefit, and evenness of the availability of drugs to the population. For a sample of commonly used best-selling drugs in the United States (US), we measured these eight access sub-dimensions across four health systems: France, the Netherlands, the United Kingdom (UK), and the US. Although the US approved between 15 and 18% more drugs than the other three countries, the US was slower than France and the UK to approve drugs licensed in all four countries. The percentage of drugs covered is approximately the same for all four countries. For covered drugs, we observe the least cost sharing by patients in the Netherlands. The Netherlands imposes conditions of reimbursement on a much larger percentage of drugs. France seems to be the slowest in respect of speed from marketing approval to reimbursement. The US is the most flexible in terms of the extent to which beneficiaries control their choice of drug benefit but it is the least universal in terms of evenness of the availability of drugs to the population. Our study confirms the frequently cited problems of access in European countries: lag between marketing approval and reimbursement, and inflexibility in respect of the extent to which beneficiaries control their choice of drug benefit. At the same time, our study confirms, qualitatively, different kinds of access problems in the US: relatively high patient cost sharing for pharmaceuticals, and wide variation in coverage.

Comparing patient access to pharmaceuticals in the UK and US.

BACKGROUND: The debate on access to new drugs has focused on the time lag between applications for approval and granting of marketing authorisation. This delay was identified as the first barrier with respect to patient access to new drugs, encompassing the hurdles of safety, efficacy and quality. Additional barriers have since been identified. These pertain to reimbursement and pricing of approved drugs, the so-called fourth and fifth hurdles. METHODS: We reviewed 38 National Institute for Health and Clinical Excellence (NICE) guidance appraisals carried out between April 1999 and April 2005. These appraisals included 71 recently approved drugs considered to have either high clinical or cost impact. For each drug we first determined its marketing approval date by the British Medicines Healthcare Products Agency (MHRA) or European Medicines Evaluation Agency (EMEA). Secondly, we determined if each drug was approved by the US FDA for marketing and, if so, the date when it was approved. Thirdly, we considered whether and when each drug was recommended for reimbursement and use by NICE, and whether conditions of reimbursement applied. Fourthly, for the subset of FDA-approved drugs, we examined formulary placement, cost sharing and conditions of reimbursement on three-tier formularies used by seven leading US third-party payers serving Medicare beneficiaries. Fifthly, we reviewed each NICE recommendation to determine if cost-effectiveness data were referred to either in the appraisal documentation or in the final recommendation. Sixthly, we asked a spokesperson from each US payer whether cost-effectiveness assessments or rebates played a role in determining formulary placement of drugs in our sample, and whether there was a lag between marketing approval and reimbursement for any of the covered drugs. RESULTS: Of the 71 drugs contained in 38 NICE guidance appraisals, the US FDA approved 64. On average, the subset of 64 drugs received marketing authorisation in the US prior to the UK. On average, US plans covered 87% of the 64 drugs, the same percentage of drugs recommended for NHS reimbursement and use. Cost sharing in the US was significantly higher than in the UK, with wider variation across plans. On average, drugs covered in the US had fewer conditions of reimbursement (15%) than the percentage of drugs given conditions by NICE (46%). US plans were quicker to decide to reimburse drugs following marketing approval than NICE. CONCLUSIONS: The US provides faster, more flexible access to most, but not all, of the UK-approved pharmaceuticals in our sample. However, US patients have higher cost sharing than the UK and coverage is less evenly spread across the population. From a policy perspective, our study findings confirm the need to bolster the NICE fast-track initiative to decrease the amount of time it takes to appraise certain new pharmaceuticals. Also, the study findings point to the need in the US for careful monitoring of plan compliance with regulations pertaining to the Medicare drug benefit, particularly with respect to formulary restrictions and limits on cost sharing.

Monoclonal antibody successes in the clinic.

Most monoclonal antibodies in clinical trials are owned by small biotech companies. But with blockbuster-sized revenues and approval rates higher than those for small-molecule drugs, that all may be set to change.