Lessons from international experience in controlling pharmaceutical expenditure. III: Regulating industry.

This is the third of three papers that review international policies to control spending on drugs and to improve the efficiency of drug use. This paper reviews policies regulating the supply of drugs, particularly licensing and reimbursement controls, price and profit regulation. Price and profit controls contain few incentives for improving cost effective use of drugs, and focus on cost containment and profitability of domestic industry. Carefully monitored economic evaluation could lead to improvements in efficiency and benefits to patients and the health care system.     

Access to Orphan Drugs: A Comprehensive Review of Legislations,Regulations and Policies in 35 Countries

ObjectiveTo review existing regulations and policies utilised by countries to enable patient access to orphan drugs.MethodsA review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country.ResultsFifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country’s legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country’s pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access.ConclusionsOverall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.     

Coding and Reimbursement for Weight Loss Surgery: Best Practice Recommendations

Objective: To review the use and usefulness of billing codes for services related to weight loss surgery (WLS) and to examine third party reimbursement policies for these services. Research Methods and Procedures: The Task Group carried out a systematic search of MEDLINE, the Internet, and the trade press for publications on WLS, coding, reimbursement, and coding and reimbursement policy. Twenty‐eight articles were each reviewed and graded using a system based on established evidence‐based models. The Massachusetts Dietetics Association provided reimbursement data for nutrition services. Three suppliers of laparoscopic WLS equipment provided summaries of coding and reimbursement information. WLS program directors were surveyed for information on use of procedure codes related to WLS. Results: Recommendations focused on correcting or improving on the current lack of congruity among coding practices, reimbursement policies, and accepted clinical practice; lack of uniform coding and reimbursement data across institutions; inconsistent and/or inaccurate diagnostic and billing codes; inconsistent insurance reimbursement criteria; and inability to leverage reimbursement and coding data to track outcomes, identify best practices, and perform accurate risk‐benefit analyses. Discussion: Rapid changes in the prevalence of obesity, our understanding of its clinical impact, and the technologies for surgical treatment have yet to be adequately reflected in coding, coverage, and reimbursement policies. Issues identified as key to effective change include improved characterization of the risks, benefits, and costs of WLS; anticipation and monitoring of technological advances; encouragement of consistent patterns of insurance coverage; and promotion of billing codes for WLS procedures that facilitate accurate tracking of clinical use and outcomes.     

Lessons from international experience in controlling pharmaceutical expenditure. II: Influencing doctors.

This is the second of three papers that review international policies to control spending on drugs and to improve the efficiency of drug use. This paper reviews policies influencing doctors'' prescribing of drugs--particularly the use of budgetary restrictions, information and feedback, and guidelines--and evaluates the impact of these policies. Studies evaluating incentive systems are limited, but evidence suggests that providing information on its own will not lead to substantial changes in practice and that more active strategies should be evaluated.     

Cancer therapy: reimbursement of new therapeutic technologies.

New drugs and technologies for cancer treatment are being developed at a rate that has created a reimbursement crisis. This article discusses third-party concerns about this problem and describes generic criteria that have proven to be useful in assessing any new technology. It is equally important to discontinue funding of ineffective and obsolete therapies as it is to devise a strategy for identifying and encouraging the development of new therapy that will be both clinically useful and cost-effective. Examples are provided to show that these are not necessarily mutually exclusive goals. Off-label application of standard therapy as well as the funding of new cancer therapy are considered. High-dose chemotherapy with autologous stem-cell support for treatment of a variety of neoplasms has become a major reimbursement challenge. Other technologies such as autolymphocyte therapy and use of colony-stimulating factors are considered in detail. Finally, a process for deciding how to fund new cancer therapy is described.     

Clinical and economic consequences of a reimbursement restriction of nebulised respiratory therapy in adults: direct comparison of randomised and observational evaluations

Objective To compare the results of a randomised and an observational evaluation of the same policy that restricted reimbursement for nebulised respiratory medications in adult patients in a community setting.Designs Cluster randomised controlled trial and observational time series with historical controls.Setting Pharmacare, the government funded drug benefits plan for elderly people and patients receiving social assistance in British Columbia, Canada.Participants In the randomised controlled trial 104 clusters of medical practices, pair matched by geography and approximately by practice size, were randomised to the intervention group (449 patients affected by the policy on 1 March 1999), and the control group (offered a six month exemption, affecting 386 patients). The observational analysis included all Pharmacare beneficiaries (excluding the 386 exempt patients) who had used any nebulised drugs six months before the policy (4624 patients).Intervention Pharmacare restricted reimbursement for nebulised bronchodilators, steroids, and cromoglycate to patients whose doctors applied for an individual patient''s exemption, giving an appropriate clinical reason.Main outcome measures Number of contacts with doctors and services, emergency admissions to hospital, and utilisation of and expenditure for respiratory drugs in databases of British Columbia''s Ministry of Health.Results Contacts with doctors or emergency admissions to hospital did not increase in association with the restriction, regardless of the analytical approach. In the observational analysis, we found a reduction of $C24 per patient month in all nebulised drug use (95% confidence interval 19 to 29) and an increase of $C3 per patient month in all expenditure for inhalers (1.4 to 4.5). The randomised evaluation found savings of $C8 per patient month for nebulisers (P = 0.24) and no increase in spending on inhalers (P = 0.79). Correcting for 60% non-compliance by exempt doctors in a sensitivity analysis yielded similar results as the observational evaluation.Conclusions Observational as well as randomised analyses found moderate net savings and no increase in unintended healthcare outcomes after restricting reimbursement for nebulised respiratory drugs. Randomised policy trials are feasible and, if carefully implemented, likely to be concordant with observational evaluations.     

Legal aspects of telepathology.

In some legal surroundings telepathology is considered a breach of registrational barriers. The recommendation of the G 8 states in Europe for required legislation in telemedicine suggests to recognise that the localization of the remote health care professional defines the site not only of licensure but also of liability. This approach must be considered helpful, since it can solve many problems brought about by the doubtful results of private international law and conventions like the European Union (EU) and Lugano Convention. Under today's conditions in private international law it must be considered essential to agree upon a choice of law and stipulate a court of jurisdiction when doing telepathology. However, the opposing aims of insuring the patients claims and avoiding jurisdictions that exceed the local expectations of the medical professional must be reconciled. Data protection and data security are other crucial topics that require attention. Generally speaking, the principles of minimum data exchange, anonymity, pseudonymity and cryptography must be established as a basis for all telepathology procedures. Only when personal data is needed, its use can be legitimated. Written consent of the patient is advised. To guarantee a cross-border security level the regulations of the EU-Data Protection Directive need to be transformed into national law. In practise, cross-border dataflow shall only take place where the security level can be maintained even within the other country. Finally, reimbursement questions must be answered to establish a sound economical basis for telepathology. The spatial distance between the participants may yield the question, whether the service has been rendered to an extent necessary and sufficient for reimbursement. If reimbursement takes place on a cross-border or cross-regional level, severe disturbances of the health systems can occur. Regulation schemes or treaties need therefore to be developed to avoid such disturbances and encompass mutual standards of care as well as methods to balance reimbursement.     

Assessment of annual health insurance reimbursement for oncology drugs in Hungary

The aim of our study is to analyse the health insurance reimbursement of oncology drugs in outpatient care, inpatient care and named patient system. Data were derived from the database of the National Health Insurance Fund Administration (OEP). The analysis covers data of pharmaceuticals with health insurance reimbursement between 1 January and 31 December, 2008. We performed the analysis according to the ATC group "L" and ICD codes C00-C99 and D00-D48. Within "L" ATC group, for ICD codes C00-C99 and D00-D48 the annual health insurance expenditure for outpatient and named patient drugs were 36.3 billion Hungarian Forints (HUF) (144.5 million EUR, 211.3 million USD). For drugs used in the acute inpatient care, we found 22.59 billion HUF (89.9 million EUR, 131.5 million USD) annual health insurance expenditure. The Hungarian National Health Insurance Fund Administration (OEP) spent altogether 58.9 billion HUF (234.4 million EUR, 342.8 million USD) for the reimbursement of oncological drugs in outpatient, named patient and inpatient care. The reimbursement of oncological drugs represents a significant expenditure for the Hungarian National Health Insurance Fund Administration (OEP). Boncz I, Donka-Verebes é, Oberfrank F, Kásler M. Assessment of annual health insurance reimbursement of oncology drugs in Hungary.     

Obstetric care,Medicaid, and family physicians. How policy changes affect physicians' attitudes.

Recent expansion of Medicaid eligibility for pregnant women and increased reimbursement to physicians who provide perinatal services were designed to improve access to care. Family physicians provide a relatively high proportion of care to pregnant women on Medicaid, especially in rural areas. We surveyed all family physicians who provide obstetric services in 26 northern California counties regarding these changes and perceived barriers to providing obstetric care to women on Medicaid. Of surveyed physicians who limited the number of their Medicaid obstetric patients, 58% stated that recent Medicaid policy changes had increased their willingness to accept new Medicaid obstetric patients. Despite these policy changes, administrative issues and poor reimbursement were cited as the two most notable barriers to providing obstetric care to women on Medicaid. Fear of being sued by Medicaid patients is still seen as a barrier by physicians who have recently discontinued practicing obstetrics and by those who continue to care for a large number of Medicaid obstetric patients.     

Benzodiazepine drugs in general medical patients.

Data from a hospital-based drug surveillance programme were used to determine how often benzodiazepine drugs were used in general medical wards. Benzodiazepines were the drugs most commonly used as hypnotics and were given to 32% of these patients. Concomitant use of more than one benzodiazepine drug or of benzodiazepines with other psychoactive drugs was common and often irrational. A series of double-blind patient-preference studies comparing various benzodiazepines and a benzodiazepine with an antihistamine showed that for short-term hypnotic effect there were no differences between three common benzodiazepines but elderly patients preferred benzodiazepines to the antihistamine, which produced more undesired effects. These results suggest that currently diazepam is the hypnotic of choice for medical ward inpatients.     

Role of drugs in traffic accidents.

Serum samples from 201 drivers who presented at emergency departments within six hours after being injured in a road accident and 325 control drivers selected randomly at petrol stations were screened for drugs by combined thin-layer and gas chromatography. Blood alcohol concentrations were also measured, and a questionnaire on the subjects'' state of health and use of drugs administered. At interview 30 patients (15%) and 44 controls (13%) said that they had taken drugs in the previous 24 hours. Four patients (2%) and six controls (2%) said that they had taken psychotropic drugs, but serum analysis detected psychotropic drugs in 10 patients (5%) and eight controls (2.5%). Diazepam was found in 16 of the 18 subjects in whom psychotropic drugs were detected. Alcohol was detected in 30 patients (15%) and three controls (1%). Drug use appeared to be somewhat lower in Finland than in other Western countries, and illness to be a more important traffic hazard than drugs in general. Interview was not a reliable method of establishing whether drivers had taken psychotropic drugs. Taking diazepam may increase the risk of being involved in a traffic accident, but alcohol was the most powerful risk factor.     

Prescribing of psychoactive drugs for chronically ill elderly patients.

The prescribing of psychoactive drugs for 1431 chronically ill elderly patients being assessed for long-term institutional or community care was surveyed. Psychoactive drugs had been prescribed for about one quarter of the patients; benzodiazepines were the most frequently prescribed group. Judging from the extensive prescribing of flurazepam and chloral hydrate, commonly used hypnotics, the main reason psychoactive drugs were prescribed was to provide night-time sedation. Antidepressants and drugs promoted as useful in improving cognitive function were infrequently prescribed. Commendable prescribing practices included the infrequent use of "cerebral vasodilators" and barbiturates. Questionable prescribing practices included the infrequent use of tricyclic antidepressants in severely depressed patients and the use of tranquilizers in patients described by their attending physician as markedly or extremely withdrawn.     

Aspirin and bleeding peptic ulcers in the elderly.

A case-control study was performed to determine whether aspirin confers a similar risk of bleeding from gastric or duodenal ulcers in the elderly as non-aspirin, non-steroidal anti-inflammatory drugs. The intake of analgesics in 230 patients with bleeding ulcers aged 60 and over and in hospital and community controls matched for age and sex was examined. Those who had taken aspirin were between two and three times more likely to be admitted to hospital with bleeding ulcers. This increased risk was not accounted for by aspirin taken for indigestion or by concurrent use of non-aspirin, non-steroidal anti-inflammatory drugs. A similar effect was not seen for paracetamol. When aspirin and other non-steroidal anti-inflammatory drugs were considered together the overall risk attributed to the drugs suggested that these drugs may be responsible for over a third of admissions for bleeding peptic ulcers in the elderly.     

Antibiotic abuse: the testimony of medical students.

Surveys of the use of antimicrobial drugs on students during antimicrobial drugs on students during their first 15 months in medical or dental school indicate that they have been treated with these agents at least three times as frequently as seems reasonable, and that the tetracyclines, ampicillin, penicillin G and erythromycin are the chief drugs overused. Antimicrobiol therapy is frequently instituted for probable viral respiratory tract infections and without any attempt to establish a bacteriologic diagnosis. It is likely that anitmicrobiol agents are used more widely in treating the general public in Canada than in treating medical students. Improvements in the rational use of this important group of drugs could increase the quality and probably reduced the cost of medical care.     

Translational genomics in personalized medicine – scientific challenges en route to clinical practice

Background

In the area of omics and translational bio(medical)sciences, there is an increasing need to integrate, normalize, analyze, store and protect genomics data. Large datasets and scientific knowledge are rationally combined into valuable clinical information that ultimately will benefit human healthcare and are en route to clinical practice. Data from biomarker discovery and Next Generation Sequencing (NGS) are very valuable and will combine in comprehensive analyses to stratify medicine and guide therapy planning and ultimately benefit patients. However, the combination into useful and applicable information and knowledge is not trivial.

NGS in personalized medicine

Personalized medicine generally promises to result in both higher quality in treatment for individual patients and in lower costs in health care since patients will be offered only such therapies that are more effective for them and treatments that will not be safe or effective will be avoided. Recent advancements in biomedical and genomic sciences have paved the way to translate such research into clinical practice and health policies. However, the move towards greater personalization of medicine also comes along with challenges in the development of novel diagnostic and therapeutic tools in a complex framework that assumes that the use of genomic information is part of a translational continuum, which spans from basic to clinical research, preclinical and clinical trials, to policy research and the analysis of health and economic outcomes. The use of next-generation genomic technologies to improve the quality of life and efficiency of healthcare delivered to patients has become a mainstay theme in the field as benefits derived from such approaches include reducing a patient’s need to go through ineffective therapies, lowering side- and off-target effects of drugs, prescribing prophylactic therapies before acute exacerbations, and reducing expenditures.

Economic challenges

As such, personalized medicine promises to increase the quality of clinical care and, in some cases, to decrease health care costs. Besides the scientific challenges, there are several economic hurdles. For instance, healthcare providers need to know, whether the approach of personalized healthcare is affordable and worth the expenses. In addition, the economic rationale of personalized healthcare includes not only the reduction of the high expense of hospitalizations, the predictive diagnostics that will help to reduce cost through prevention or the increased efficacy of personalized therapies needs to offset prices of drugs. There are also several factors that influence payer adoption, coverage and reimbursement; the strength of evidence drives payers‘ decisions about coverage and reimbursement, varies widely depending on the personalized healthcare technology applied and regulation and cost-effectiveness seem to be increasingly associated with reimbursement, which is strongly influenced by professional society guidelines. In general, we see the following main obstacles to the advancement of personalized medicine: (i) the scientific challenges (a poor understanding of molecular mechanisms or a lack of molecular markers associated with some diseases, for example), (ii) the economic challenges (poorly aligned incentives), and (iii) operational issues in public healthcare systems. The operational issues can often be largely resolved within a particular stakeholder group, but correcting the incentive structure and modifying the relationships between stakeholders is more complex.

En route to clinical practice

This article focuses on the scientific difficulties that remain to translate genomics technologies into clinical practice and reviews recent technological advances in genomics and the challenges and potential benefits of translating this knowledge into clinical practice, with a particular focus on their applications in oncology.

Electronic supplementary material

The online version of this article (doi:10.1186/1877-6566-6-2) contains supplementary material, which is available to authorized users.     

Comparative evaluation of the clinical effectiveness of 3 preparations of E. coli L-asparaginase

Preparations of L-asparaginase made in the USSR, FRG and Japan were studied comparatively in 277 patients with acute lymphoblastic leukemia and lymphosarcomas. It was shown that the clinical characteristics of the preparation made in the USSR and the preparation (crasnitin) made in the FRG were identical. By the antileukemic action the preparation made in the USSR was superior to the preparation (leunase) made in Japan in the treatment of adult patients with such hemoblastosis forms. The effect of the three drugs in the treatment of children was analogous. The nature of the side effects of the three drugs was the same. However, their level was different. The allergenic effect of leunase on the patients was the most pronounced. L-Asparaginase made in the USSR and crasnitin are recommended for wide use in clinical practice.