Cost Of New Drugs Research Articles

Metalloantimalarials: targeting of P. falciparum strains with novel iron(III) and gallium(III) complexes of an amine phenol ligand.

Emergence of chloroquine (CQ)-resistant Plasmodium falciparum strains necessitates discovery of potent and inexpensive antimalarial drugs. The high cost of new drugs negatively impacts their access and distribution in the regions of the world with scarce economic resources. While exploring structure-activity relationships, using gallium(III) as a surrogate marker for iron(III), we found cationic, and moderately hydrophobic, compounds, [[1,12-bis(2-hydroxy-3-ethyl-benzyl)-1,5,8,12-tetraazadodecane]metal(III)](+) (metal = Fe(III) and Ga(III); [Fe-3-Eadd](+), 3; [Ga-3-Eadd](+), 4), that possessed antimalarial activity. Crystal structure analyses revealed octahedral geometry for these complexes. The RP-HPLC analysis, after incubation in PBS or HEPES buffer (pH 7.4) at 37 degrees C for 3 days, detected only parental compounds thereby providing evidence for stability under physiological conditions. Both 3 and 4 demonstrated promising half-maximum inhibitory concentration (IC(50)) values of approximately 80 and 86 nM in the CQ-sensitive HB-3 line, respectively. However, both 3 and 4 were found to possess elevated IC(50) values of 2.5 and 0.8 microM, respectively, in the CQ-resistant Dd2 line, thus displaying preferential cytotoxicity toward the CQ-sensitive HB3 line. In cultured parasites, 3 and 4 targeted hemozoin formation. Thus, these compounds acted similarly to chloroquine with regard to action and resistance, despite the lack of structural similarity to quinolines. Finally, similarity in coordination chemistry, stability, and antimalarial cytotoxicity profiles indicated that gallium(III) ion can serve as a template for iron(III) in structure elucidation of active molecules in solution.

The value of improving the productivity of the drug development process: faster times and better decisions.

This study examines the financial benefits that can accrue to drug developers from improvements in the drug development process. The effect on drug development costs from faster development, earlier decisions on project failures, and higher approval success rates are quantified. The results from a recent study of research and development (R&D) costs for new drugs are used as a benchmark against which improvements in the discovery and development processes are simulated. The cost results in the benchmark study were based on a sample of 68 randomly selected investigational drugs from 10 pharmaceutical firms. Simultaneous 25% reductions in phase lengths lower capitalized total cost per approved drug by 16%, or $US129 million; 50% reductions in time lower cost by 29%, or $US235 million. Earlier decisions to terminate research on drugs that will ultimately fail significantly reduce clinical costs. For example, shifting 5% of all clinical failures from phase III/regulatory review to phase I reduces out-of-pocket clinical costs by 5.5 to 7.1%; and capitalized clinical cost is lowered by 5.1 to 6.3%. If more productive discovery programmes or better preclinical screens increase success rates from 21.5% to one in three, firms can reduce capitalized total cost per approved drug by $US221 million to $US242 million. Whether faster development times, quicker termination decisions or higher success rates derive from public policy initiatives, better management, or new technologies, the impact on R&D costs can be substantial. Ultimately, the increased efficiency could result in more innovation and new therapies reaching patients sooner.

Pharmacoeconomics in anaesthesia

Newer anaesthetic agents provide a faster onset, easier titration and a more rapid recovery than the older agents, but are more expensive. In assessing the financial consequences associated with their use, it is important to examine the total costs (including personnel costs) and not just the acquisition costs of new drugs. Claims of cost savings from new drugs should be subjected to close scrutiny, with studies designed to demonstrate that the preferential use of the newer drug is associated with actual decreased payments for personnel, an earlier return to normal activities by the patient and/or their caretakers, or the completion of an additional case in the same operating session. It may be necessary to alter work patterns to obtain the full benefits of the new drugs (e.g. bypass of the labourintensive [phase I] postanaesthetic care unit). Finally, greater cost savings in the operating room can be achieved by increasing efficiency in resource utilization. A delay in starting a case, or a prolonged turnover time between cases, can negate any cost savings related to the anaesthetist's choice of drugs.

Pharmacoeconomics in anaesthesia: what are the issues?

Summary Newer anaesthetic agents provide a faster onset, easier titration and a more rapid recovery than the older agents, but are more expensive. In assessing the financial consequences associated with their use, it is important to examine the total costs (including personnel costs) and not just the acquisition costs of new drugs. Claims of cost savings from new drugs should be subjected to close scrutiny, with studies designed to demonstrate that the preferential use of the newer drug is associated with actual decreased payments for personnel, an earlier return to normal activities by the patient and/or their caretakers, or the completion of an additional case in the same operating session. It may be necessary to alter work patterns to obtain the full benefits of the new drugs (e.g. bypass of the labour-intensive [phase I] postanaesthetic care unit). Finally, greater cost savings in the operating room can be achieved by increasing efficiency in resource utilization. A delay in starting a case, or a prolonged turnover time between cases, can negate any cost savings related to the anaesthetist's choice of drugs.

Pharmacoeconomics in anaesthesia: what are the issues?

Newer anaesthetic agents provide a faster onset, easier titration and a more rapid recovery than the older agents, but are more expensive. In assessing the financial consequences associated with their use, it is important to examine the total costs (including personnel costs) and not just the acquisition costs of new drugs. Claims of cost savings from new drugs should be subjected to close scrutiny, with studies designed to demonstrate that the preferential use of the newer drug is associated with actual decreased payments for personnel, an earlier return to normal activities by the patient and/or their caretakers, or the completion of an additional case in the same operating session. It may be necessary to alter work patterns to obtain the full benefits of the new drugs (e.g. bypass of the labour-intensive [phase I] postanaesthetic care unit). Finally, greater cost savings in the operating room can be achieved by increasing efficiency in resource utilization. A delay in starting a case, or a prolonged turnover time between cases, can negate any cost savings related to the anaesthetist's choice of drugs.

American health care: government, market processes, and the public interest

President Clinton's health care reform proposals of 1993 represented the most far-reaching program of social engineering attempted in the United States since the passage of Medicare and Medicaid in 1965. Under the guise of reforming the health care system, the Clinton plan would have herded almost all Americans under age sixty-five into large, government-sponsored health insurance purchasing alliances that would have contracted with insurers to offer a standard set of benefits at regulated prices. The plan came under fire from both Republicans and Democrats, including moderates from both parties, but it soon became apparent that what doomed it was a public unwilling to trust government to manage their health care. The critical literature has failed to offer a cogent analysis of why government control of health care does not work. American Health Care delivers that analysis. This volume examines why untoward consequences usually follow when government sets out to do good things. The contributors demonstrate how hospital rate regulation raises hospital prices, that no-fault medical malpractice increases the occurrence of faulty medicine, and that FDA regulation is a major cause for the escalating cost of new drugs. Part 1, trace the genesis of Medicare and its later developments and argue the consumer advantages of medical savings accounts and written health contracts. Part 2, explore the fallacies of antitrust policies that serve the interests of competitors, attack community rating for making health insurance unaffordable to large numbers of young workers. Part 3, contains a powerful critique of the FDA for withholding vital information on the health benefits of aspirin and shows how HMOs and other plans have caused pharmaceutical marketing to shift its focus from medical effectiveness to cost effectiveness. The final section explores how the private sector is improving in the areas of regulating physician and other health professional fees and the supply and quality of health professionals. American Health Care proposes reasonable balances between government and market options for in supply of health services. Without denying the need for some governmental action, the contributors show how far the market can go farther in performing critical functions in the health care industry. This volume will be important reading for health policymakers, economists, and health care professionals.

Problems with the interpretation of pharmacoeconomic analyses: a review of submissions to the Australian Pharmaceutical Benefits Scheme.

Pharmacoeconomic analyses are being used increasingly as the basis for reimbursement of the costs of new drugs. Reports of these analyses are often published in peer-reviewed journals. However, the analyses are complex and difficult to evaluate. To describe the nature of problems encountered in the evaluation and interpretation of pharmacoeconomic analyses used as a basis for reimbursement decisions. All major submissions to the Department of Health and Aged Care (DHAC) by the pharmaceutical industry for funding made under the Australian Pharmaceutical Benefits Scheme. Specifically, the DHAC's database of submissions that were received between January 1994 and December 1997 were reviewed. Of a total of 326 submissions, 218 had serious problems of interpretation and were included in the analysis. The nature of the serious problems reviewed were classified as estimates of comparative clinical efficacy, comparator issues, modeling issues, and calculation errors. All submissions in the DHAC's database were reviewed and data were extracted if both the DHAC evaluators and technical subcommittee considered problems to have a significant bearing on the decisions of the parent committee. Of a total of 326 submissions, 218 (67%) had significant problems and 31 had more than 1 problem. Of the 249 problems identified, 154 (62%) related to uncertainty in the estimates of comparative clinical efficacy, and 71 (28.5%) related to modeling issues, which included clinical assumptions or cost estimates, used in the construction of the economic models. There were 15 instances of disagreement over the choice of comparator, and serious calculation errors were found on 9 occasions. Overall, 159 problems (64%) were considered to be avoidable. Significant problems were identified in these pharmacoeconomic analyses. The intensive evaluation process used in the Australian Pharmaceutical Benefits Scheme allowed for identification and correction of pharmacoecomomic analysis problems, but the resources that are required may be beyond the capacity of many organizations, including peer-reviewed journals.

Clinical development projects in the biotechnology industry

A major portion of both the time and cost of new drug and biological product development is the series of human clinical studies required to determine the safety and effectiveness of the drug before it can be marketed. This paper analyses data from 68 new drug and biological product development projects sponsored by US-based biotechnology companies over a period of 19 years, from 1979 to 1998. The type of collaboration in place for each project and the size of the sponsoring company were assessed for potential effects on the projects' clinical development times. While there was no statistical difference among the type of collaboration, the data shows evidence of a trend toward shorter clinical development times for drug development projects without a collaborative partner. Findings also indicated a significantly shorter clinical development time for projects sponsored by medium size versus small or large biotechnology companies. The results offer insight into the process of new drug development, along with pertinent information regarding resources that may help lead to success in the effort to reduce time involved in human clinical studies.

The changing role of the psychiatrist in board-and-care homes.

The role of the psychiatrist in board-and-care homes has been changing dramatically since a job description was published in 1989. The role has become more complex as a result of advances in psychopharmacology, the trend toward polypharmacy regimens, the necessity to evaluate the interaction potentials of drug combinations, and the emergence of more sophisticated treatment algorithms. Broad social trends have added to the complexity of board-and-care treatment, such as the tendency to release more severely disturbed patients from long-term-care facilities because of the increasing costs associated with institutionalization. However, treatment of these patients will continue to be expensive because of the higher costs of new drugs and of using medication combinations. Continued high-cost treatment will increase pressure to control costs by managed care companies, third-party payers, and government agencies. Although this paper describes the effects of these trends on board-and-care psychiatrists, they are also relevant to psychiatrists in general and to other practitioners.

Is the introduction of new anesthetic drugs and techniques economically justified?

Newer anesthetic agents provide for a faster onset, easier titration, and a more rapid recovery than the older agents, but are more expensive. In assessing the financial consequences associated with their use, it is important to examine the total costs (including personnel costs) and not just the acquisition costs of new drugs. Claims of cost savings from new drugs should be subjected to close scrutiny, with studies designed to show that the preferential use of the newer drug is associated with actual decreased payments for personnel, an earlier return to normal activities by the patient and their caretakers, or the treatment of an additional patient in the same operating room session. It may be necessary to alter work patterns to obtain the full benefits of the new drugs (e.g. bypass of the labor-intensive phase I postanesthetic care unit). Finally, greater cost savings in the operating room can be achieved by increasing efficiency in resource use. A mere 30-min delay in starting to treat a patient can negate any cost savings related to the anesthesiologist's choice of drugs.

The economics of lung cancer management in Canada.

Because lung cancer is a major health care problem in Canada, it is imperative to understand how resources are used to diagnose and treat this disease. This paper describes a method of modelling the direct patient care costs for lung cancer from the perspective of the government as payer in a universal health care system. Clinical algorithms were developed to describe the management of non-small cell (NSCLC) and small cell (SCLC) lung cancer. Patients were allocated to the treatment algorithms in the model based on a knowledge of their distribution by cell type and stage in Canadian cases. A microsimulation model developed by Statistics Canada was used to integrate the data on type of lung cancer, extent of disease, clinical management, survival and health care resource utilization. The direct care costs for diagnosis and treatment of NSCLC ranged from $Cdn 17 889 for the surgery/post-operative radiotherapy treatment of Stages I and II to $Cdn 6333 for supportive care for patients with Stage IV disease. The costs of determining relapse for NSCLC were estimated to be $Cdn 1528 and terminal care costs, made up largely of hospitalization charges and some palliative radiotherapy, were $Cdn 10 331. Direct care costs for the diagnosis and initial treatment of SCLC ranged from $Cdn 18 691 for management of limited stage disease to $Cdn 4739 for the supportive care of patients with extensive disease. The cost of determining relapse for SCLC was estimated to be $Cdn 1590 and terminal care costs averaged $Cdn 9966. For all 15 624 cases of lung cancer diagnosed in Canada in 1988, it was estimated that the total cost of providing treatment and follow-up, and managing relapse over 5 years was $Cdn 328 million. Despite the large total cost of lung cancer management, estimates of cost effectiveness of therapy showed that the cost per life year gained was approximately $Cdn 11 000 for NSCLC and $Cdn 19 560 for SCLC. These estimates of the direct health care costs assume that all patients have access to care, treatment is uncomplicated and practice is standard, and must be viewed as an idealized assessment of the cost of lung cancer management. The microsimulation model, however, does provide a useful framework for evaluating the costs of new diagnostic procedures, treatment strategies and new drugs.

Influences on the Quality of Published Drug Studies

To practice evidence-based medicine, physicians need data on the clinical effectiveness, toxicity, convenience, and cost of new drugs compared with available alternatives. We give examples of published drug studies that are defective, sometimes because pharmaceutical industry funding has affected their content and quality. We make recommendations on how to avoid these defects.

Research and Development Costs for New Drugs by Therapeutic Category

The clinical period (i.e. clinical trial and long term animal testing) development costs of a random sample of new chemical entities (NCEs) were examined for differences in average cost. All of the NCEs studied were first tested in humans between 1970 and 1982, and were classified for the purposes of the study by therapeutic class. The costs of unsuccessful projects were included with those of projects that resulted in US marketing approval. Including income forgone from expending funds before returns are earned ('time costs'), the capitalised (i.e. out-of-pocket plus time) clinical period costs per approved NCE were $US70, $US98, $US103 and $US163 million (1993 dollars) for anti-infective, cardiovascular, neuropharmacological and nonsteroidal anti-inflammatory drugs, respectively. Combining the data for all therapeutic categories, the mean clinical period cost per approved NCE was $US93 million. Omitting costs associated with unsuccessful projects, the mean capitalised clinical period costs for approved NCEs ranged from $US7.1 million (for topical steroids) to $US66.7 million (for cardiovascular agents) [1993 dollars]. The estimates of total clinical period costs per approved NCE depend on average out-of-pocket clinical phase costs, attrition rates across phases (i.e. the rates at which compounds drop out of active testing), the probability of marketing approval, and development and regulatory review times. Phase attrition and approval rates are the most important sources of variability in total clinical period costs between therapeutic categories. Development cost estimates by therapeutic category did not correlate strongly with US sales in the fifth year of marketing. Cardiovascular NCEs had much higher than average sales revenues, but clinical development costs for these drugs were only slightly above average. Conversely, nonsteroidal anti-inflammatory drugs attained average sales revenues, but had much higher than average development costs.

Rising research and development costs for new drugs in a cost containment environment.

The concurrence in recent years of mounting pressures to contain pharmaceutical expenditures in the United States and Europe, and rising research and development costs for new drugs, raises concerns about the future of new drug development. A recent study has shown that the research and development expenditures required to get new drugs to the marketplace are high and have been increasing rapidly. A random sample of 93 new chemical entities (NCEs) first tested in humans in 1970 to 1982 yielded an estimate for the cost per approved NCE of US$231 million in 1987 dollars. This estimate is more than double, in constant dollars, that of a previous study that used a similar methodology and covered a period roughly one decade earlier. The 2 studies were analysed to determine the components of the cost increase, and some of the more fruitful areas for future research on research and development costs are discussed.

Plaque disruption and thrombosis in unstable angina pectoris

Therapeutic strategies and clinical trials in unstable angina should be based on the pathogenesis, risk, and mechanisms of thrombosis. The mechanisms of thrombosis and the differences in the effects of anticoagulant, antithrombotic, antifibrin, and antiplatelet drugs must be taken into account when determining the dosage and duration of therapy. Ignoring these principles may prevent identification of new therapy, increase the cost of new drug development and research, increase the cost of new drugs, and increase the cost of medical care.

The cost of new drugs in the treatment of hypertension — The Australian experience

The treatment of hypertension by costly new drugs such as the angiotensin converting enzyme inhibitors, means that careful monitoring of health care expenditure is essential. If drugs like simvastatin come to be widely used, costs will mount even more. New drugs cannot be used indiscriminately.

Science: part of the problem, most of the answer.

The history of the drug approval process in the United States includes three phases. First, the Food and Drug Act of 1906 essentially required that the labeling of drugs be truthful. The 1938 Food, Drug, and Cosmetic Act added a requirement that drugs be proven safe, and the 1962 act added the requirement that drugs be efficacious. Each of these steps required more and more sophisticated science. Subsequent to the Kefauver-Harris Amendments of 1962, the number of innovative molecular entities each year has declined, the reasons for which have been subject to great debate. This decline has paralleled decreases in innovation across almost all American industry, leading to questions about the future of our country as an industrialized society. Both the Carter and Reagan administrations attempted to address this problem in a number of ways, including cutting back on those regulations that are perceived as unnecessary. Other innovative approaches have been used, such as the establishment of an Office of Small Manufacturers Assistance in the FDA Bureau of Medical Devices, mandated by the 1976 Medical Device Amendments. The latter came about in recognition of the fact that small businesses tend to be more creative and efficient than larger industries and more adversely affected by regulation. However, the problems raised in the regulation of technology transfer almost inevitably arise because of perceived scientific questions. Such questions, in turn, can only be answered by good science performed by the sponsor and understood by the regulator. Thus, it is essential that the FDA be staffed with knowledgeable scientists who can interact easily with their peers in academia and industry. Although science is often the cause of our troubles, it is also our only hope for minimizing the costs of new drugs and other technology. In turn, minimizing such costs will maximize the opportunities for innovation.