Prescription costs

Prescription costs are a common health care cost for many people and also the source of considerable economic hardship for some.[1] These costs are sometimes referred to as out-of-pocket prescription costs, since for those with insurance, the total cost of their prescriptions may include expenses covered by a third party, such as an insurance company, as well as the individual. Out-of-pocket prescription costs include deductibles, co-payments, and upper limits in coverage.

Drug pricing factors

Drug costs in different countries[2]
Drug US Canada UK Spain Netherlands
Enbrel $2,225 $1,646 $1,117 $1,386 $1,509
Celebrex $225 $51 $112 $164 $112
Copaxone $3,903 $1,400 $862 $1,191 $1,190
Cymbalta $194 $110 $46 $71 $52
Humira $2,246 $1,950 $1,102 $1,498 $1,498
Nexium $215 $30 $42 $58 $23

Pricing any pharmaceutical drug for sale to the general public is daunting. Per Forbes, setting a high ceiling price for a new drug could be problematic as physicians could shy away from prescribing the drug, because the cost could be too great for the benefit.[3] Setting too low of a price could imply inferiority, that the drug is too "weak" for the market.[3] There are many different pricing strategies and factors that go into the research and evaluation of a future drug’s price with whole departments within US pharmaceutical companies like Pfizer devoted to cost analysis. Regardless of the pricing strategy the common theme within all factors is to maximize profits.

This chart shows discrepancies in drug pricing in different countries, which indicates differences in both market conditions and government regulation. For instance, Canada has a drug ceiling price that drug prices cannot exceed.

Research and development

The table shows research and development statistics for pharmaceutical companies as of 2013 per Astra Zeneca.[4]

Pharmaceutical company Number of drugs approved Average R&D spending per drug (in $ Millions) Total R&D spending from 1997-2011 (in $ Millions)
AstraZeneca 5 $11,790.93 $58,955
GlaxoSmithKline 10 $8,170.81 $81,708
Sanofi 8 $7,909.26 $63,274
Roche Holding 11 $7,803.77 $85,841
Pfizer 14 $7,727.03 $108,178
Johnson & Johnson 15 $5,885.65 $88,285
Eli Lilly & Co. 11 $4,577.04 $50,347
Abbott Laboratories 8 $4,496.21 $35,970
Merck & Co Inc. 16 $4,209.99 $67,360
Bristol-Meyers Squibb Co. 11 $4,152.26 $45,675
Novartis 21 $3,983.13 $83,646
Amgen Inc. 9 $3,692.14 $33,229

Severin Schwan, the CEO of the Swiss company Roche, reported that Roche’s research and development costs amounted to $8.4 billion, a quarter of the entire National Institutes of Health budget.[3] Given the profit-driven nature of pharmaceutical companies and their research and development expenses, companies use their research and development expenses as a starting point to determine appropriate yet profitable prices.

Pharmaceutical companies spend a large amount on research and development before a drug is released to the market and costs can be further divided into three major fields: the discovery into the drug’s specific medical field, clinical trials, and failed drugs.[5]

Discovery

Drug discovery is the area of research and development that amounts to the most amount of time and money. The process can involve scientists to determine the germs, viruses, and bacteria that cause a specific disease or illness.[6] The time frame can range from 3–20 years and costs can range between several million to tens of millions of dollars. Research teams attempt to break down disease components to find abnormal events/processes taking place in the body.[6] Only then do scientists work on developing chemical compounds to treat these abnormalities with the aid of computer models.[6]

After "discovery" and a creation of a chemical compound, pharmaceutical companies move forward with the Investigational New Drug (IND) Application from the FDA.[6] After investigation into the drug and given approval, pharmaceutical companies can move into pre-clinical trials and clinical trials.[6]

Trials

Drug development and pre-clinical trials focus on non-human subjects and work on animals such as rats. This is the most inexpensive phase of testing.

The Food and Drug Administration mandates a 3 phase clinical trial testing that tests for side effects and the effectiveness of the drug with a single phase clinical trial costing upwards of $100 million.[7]

After a drug has passed through all three phases, the pharmaceutical company can move forward with a New Drug Application from the FDA. In 2014, the FDA charged between $1 million to $2 million for an NDA.[8]

Failed drugs

The processes of "discovery" and clinical trials amounts to approximately 12 years from research lab to the patient, in which about 10% of all drugs that start pre-clinical trials ever make it to actual human testing.[6] Each pharmaceutical company (who have hundreds of drugs moving in and out of these phases) will never recuperate the costs of "failed drugs". Thus, profits made from one drug need to cover the costs of previous "failed drugs".

Relationship

Overall, research and development expenses relating to a pharmaceutical drug amount to the billions. For example, it was reported that AstraZeneca spent upwards on average of $11 billion per drug for research and developmental purposes.[7] The average of $11 billion only comprises the "discovery" costs, pre-clinical and clinical trial costs, and other expenses. With the addition of "failed drug" costs, the $11 billion easily amounts to over $20 billion in expenses. Therefore, an appropriate figure like $60 billion would be an approximate sales figure that a pharmaceutical company like AstraZeneca would aim to generate in order to cover these costs and make a profit at the same time.

Total research and development costs provide pharmaceutical companies a ballpark estimation of total expenses. This is important in setting projected profit goals for a particular drug and thus, is one of the most basic steps pharmaceutical companies take in pricing a particular drug.

Benefits and side effects

Drugs are made with the intention of curing, treating, or preventing a condition, disease, or illness. This is done either by "adding" or "deleting" something within the human body. Although all drugs incur side effects, these side effects are weighed heavily against the benefit the drug brings. Oftentimes, companies will examine the net gain. If there is a serious net gain, pharmaceutical companies can justifiably charge a premium. However, if the net gain is marginal, it would be unreasonable to give a drug an astronomically high price if there are serious side effects or if the benefits are not too great.

The drug Lipitor (Calcium atorvastatin), renowned for lowering cholesterol levels, can cause many typical drug side effects such as constipation, diarrhea, nausea, fatigue, gas, heartburn, headache, and memory loss.[9] The ability to lower cholesterol levels is objectively and unmistakably worth the side effects and thus, Pfizer can charge a premium over its long term 20 year patent.

Companies can also look at these side effects and compare them to the side effects of other competitor drugs on the market. If the effects are comparatively better than a competitor, prices can rise without much penalty. However, if there are more side effects, the pharmaceutical must charge significantly less. For example, Lipitor’s competition is generic simvastatin, known to be a cheaper alternative (Lipitor sells for $1 a day without insurance while simvastatin is roughly 50 cents a day).[10] The side effects of simvastatin are generally the same as Lipitor, except that simvastatin may also induce sleep problems and even depression. Hence, simvastatin must be priced at half of Lipitor's worth as it has more deleterious side effects.

Patents and competition

Monopoly rights and incentives

One of the most important factors that determine the cost of a drug is the availability of competing drugs and treatments. Having two or more manufacturers producing drugs for the same disease tends to reduce costs.[3]

Patent laws give pharmaceutical companies the exclusive right to market a drug for a period of time, allowing them to extract a high monopoly price. For example, U.S. patent law grants a monopoly for 20 years after filing. After that period, the same product from different manufacturers - known as generic drugs - can be sold, usually resulting in a substantial price reduction and possible shift in market share. In some cases, a new treatment is more effective than an older treatment, or a given drug may work better than competitors for only some patients. The availability of an imperfect substitution erodes prices to a lesser degree than would a perfect substitute.

Some countries grant additional protections from competition for a limited period, such as test data exclusivity or supplementary protection certificates. Additional incentives are available in some jurisdictions for manufacturers of orphan drugs for rare diseases, including extended monopoly protection, tax credits, waived fees, and relaxed approval processes due to the small number of affected patients.

Example

[11] Chart showing projected drops and revenues after a patent window expires

An example of the power of patent protection can be seen in the world's best-selling drug of all time, Lipitor. This drug did something else no other cholesterol drug at the time could do, increasing levels of HDL (good cholesterol) in addition to decreasing levels of LDL (bad cholesterol) faster than any other statin on the market.[12] Pfizer used a patent to protect this approach, and for 20 years, an enormous profit was seen.[11] After loss of exclusivity in November 2011, Pfizer saw a 59% drop in revenue for the drug in 2012,[13] with further declines predicted.

Rationale

The ability to command a monopoly price is a reward granted by patent law for the invention of new, useful technology. Research and development of new drugs is quite risky - most candidates don't prove to be safe and effective. The necessary medical research, development of chemical manufacturing process, and clinical trials typically cost hundreds of millions or billions of dollars for each successful drug. Patent protection allow companies to recoup these costs and earn monopoly profits as an incentive to tolerate the high risk and to invest in life-saving drugs as opposed to other business ventures. Net profits from successful drugs also cover the cost of research and development for failed drugs, and can provide seed funding for future drugs. Without patent protections or an alternative funding mechanism, many life-saving treatments would simply not be invented, due to lack of the ability to recover R&D costs in a fully competitive market. Because patents are public, the monopoly protection also acts as a reward for disclosure of the methods to produce a drug, its structure, and data about its usefulness and safety. This disclosure enables generic manufacturers to re-create the drug (though often the patent holder discloses as little as possible, to retain some competitive advantage) and enables further research into the disease by other parties.

Test data exclusivity is a substantial incentive to promote running of clinical trials for substances which cannot be patented because of prior art or being generally known. This allows known substances to gain approval for additional diseases, whether rare or common.

Patient access problems and alternatives

The limited duration of patents is intended to ensure that, in the long run, consumers have access to new drugs at competitive market prices rather than monopoly prices. In the short term, the high cost of drugs during period of monopoly protection is seen as an ethical problem when it prevents some patients from accessing treatments that could prevent serious injury or death. One extreme example is Harvoni, which in the United States typically costs $90,000 for an 8-12 week round of treatment that has a 94% to 99% success rate in curing type 1 hepatitis C. In countries with a single-payer healthcare system, these costs may be absorbed by the government (possibly after negotiating or mandating a lower price). In countries with private insurance, patients are subject to deductibles and co-payments which can be unaffordable for high-cost treatments for those with low incomes, and those without patients would bear the full cost. The enormous cost of curing hepatitis C has even lead some insurance companies and government agencies in the United States to ration care by asking patients to wait for the treatment until they have some evidence of liver damage.

Some drug manufacturers have been accused of extending their monopolies to the detriment of consumers. Evergreening of patents involves filing related patents with later expiration dates. With so-called pay for delay schemes, patent holders pay generic manufacturers to remain out of the market for a longer period of time, though this technique has been challenged as a violation of anti-trust laws.

People and governments in developing countries have far fewer financial resources to bear high monopoly prices. Drug prices even for patent-protected medicines in these countries are often considerably lower, and profits are often insubstantial and do not proportionally cover development costs. In many cases, a patent holder will license generic manufacturers to sell to low-income countries at low cost. Some developing countries (notably India) have less restrictive patent regimes which make manufacture of generic medications possible sooner, for sale domestically or in other countries where the patent protections do not apply. Typically the cost of making small-molecule drugs is only a very small portion of a developed-country market monopoly price, which makes generic manufacturing very cheap. In contrast, some drugs are inherently expensive to produce, such as the biopharmaceutical drug Cerezyme, typically costing $200,000 per year in the United States.

Some pharmaceutical companies have patient assistance programs,[14] a form of financial aid where drugs are provided at a discount or free of charge where they would otherwise have been unable to afford treatment. For some rare diseases, the manufacturer of an important treatment has committed to ensuring access to every single patient of the disease worldwide. Some low-volume treatments are provided free of charge to all patients.[15]

There has been some concern that competition among generic manufacturers is insufficient to drive prices close to the cost of production. Many-fold increases in the price of existing treatments such as Daraprim, Alcortin A, Novacort, and epinephrine autoinjectors have caused considerable controversy.[16][17] Reliance on a small number of manufacturing plants can also result in drug shortages; the U.S. FDA noted a record number of shortages in 2010, largely due to quality and manufacturing problems.[18] Doctors Without Borders is actively lobbying for reductions in the cost of both generic and patent-protected vaccines and treatments for tuberculosis and HIV/AIDS in developing countries.[19]

People with neglected tropical diseases reside almost entirely in developing countries, resulting in limited profit incentives for private developed-country drug companies to invest in treatment candidates. Some infectious diseases are only sporadic threats, providing little opportunity for profit in advances of an outbreak, but necessitating immediate response when one occurs. Pointing out these market failures and access problems created by patent monopolies, some critics have proposed patent reforms or replacement funding mechanisms such as prizes as an alternative to patents. A similar funding mechanism is a guaranteed-purchase announcement, or stockpiling as with the U.S. Strategic National Stockpile. Infectious diseases that pose an international threat as natural epidemics or bioweapons, such as Ebola or anthrax receive government funding to develop vaccines and respond to outbreaks, either through grants to independent labs or through agencies like the U.S. Centers for Disease Control and Prevention. Neglected diseases and others of concern to developing countries receive direct research and production funding through international aid programs like the U.S. President's Emergency Plan for AIDS Relief, donations from pharmaceutical companies, and non-profits like the Bill & Melinda Gates Foundation, the Carter Center, the Schistosomiasis Control Initiative, and the International Trachoma Initiative.

Stakeholders

Patients and doctors can also have some input in pricing, though indirectly. Customers in the United States have been protesting the high prices for recent "miracle" drugs like Daraprim and Harvoni, both of which attempt to cure or treat major diseases (HIV/AIDS and Hepatitis C).[20] Public outcry has worked in many cases to control and even decide the pricing for some drugs. For example, there was severe backlash over Daraprim, a drug that treats toxoplasmosis.[21] Turing Pharmaceuticals under the leadership of Martin Shkreli price gouged the drug 5,500% from $13.50 to $750 per pill.[21] After denouncement from 2016 presidential candidates Hillary Clinton and Bernie Sanders, Turing Pharmaceuticals finally decided to reduce the price.[21]

With the recent trend of price gouging, legislators have even introduced reform to curb these hikes, affectively controlling the pricing of drugs in the United States. Hillary Clinton announced a proposal to help patients with chronic and serious health conditions by placing a nationwide monthly cap of $250 on prescription out-of-pocket drugs.[21]

Research for a drug that is curing something no one has ever cured before will cost much more than research for the medicine of a very common disease that has known treatments. Also, there would be more patients for a more common ailment, so prices would be lower. Soliris only treats two extremely rare diseases, so the number of consumers is low, making it an orphan drug. Soliris still makes money because of its high price of over $400,000 per year per patient.[3] The benefit of this drug is immense because it cures very rare diseases that would cost much more money to treat otherwise, which actually saves insurance companies and health agencies millions of dollars. Hence, insurance companies and health agencies are willing to pay these prices.

United States

In the period 1994–2004 prescription costs were the most rapidly increasing cost of health care in the United States. These increases, which averaged 12% during some years, are accounted for by increases in the number of drugs per person (treatment intensification), increases in the cost of a "market-basket" of drugs (price inflation), and increases in the use of newer drugs over older, less costly, alternatives.[22] Overall, experts estimate that treatment intensification increased by 68% and price inflation increased by 8.3% between 1994 and 2004.

A substantial body of evidence has documented the association between high out-of-pocket costs and many types of economic and non-economic hardship. Between 20%–30% of patients in the United States report having skipped or stretched a prescription medicine during the previous 12 months because of the cost. Other patients report cutting back on payments for their utilities or food in order to afford their prescription medicines. In 2011 and 2012, approximately 2% of individuals reported purchasing prescription drugs from another country to save money.[23] A predictive index has been developed that differentiates individual risk of importing prescription drugs for personal use, thus potentially allowing policymakers to target resource-efficient interventions that minimize the potential risks of importation and improve access to affordable prescription medicines.[24]

Patients may be embarrassed to raise their concerns about the cost of drugs, concerned that doing so may compromise their quality of care, or under the impression that there is nothing that their health care provider can do to help. Providers may also be embarrassed discussing costs, and feel too much time pressure to discuss these costs with patients.

United Kingdom

A very large number of people in the countries of the United Kingdom get prescriptions partly or totally paid for by the National Health Service.[25] In Scotland, Wales and Northern Ireland prescriptions are free to all citizens. While in England prescribed medicines and medical supplies are free of charge to:

For others each prescribed item, regardless of nature or quantity, costs £8.20. One exception to this is if two items are prescribed of the same drug in the same form at different strengths (e.g. Ramipril 2.5mg capsules and Ramipril 5mg capsules) which would only incur one charge if they are printed on the same prescription. A prescription pre-payment certificate (or PPC) can be bought for £104.00, and covers unlimited prescriptions for 12 months. Alternatively, 3-monthly PPCs may be bought for £29.10 (Prices as of 1 April 2013). PPCs are sold to the public by the NHS Business Services Authority.

Developing world

In many developing countries the cost of proprietary drugs is beyond the reach of the majority of the population.[26] There have been attempts both by international agreements and by pharmaceutical companies to provide drugs at low cost, either supplied by manufacturers who own the drugs,[27] or manufactured locally as generic versions of drugs which are elsewhere protected by patent.[28] Countries without manufacturing capability may import such generics.

The legal framework regarding generic versions of patented drugs is formalised in the Doha Declaration on Trade-Related Aspects of Intellectual Property Rights and later agreements.

Expenditures by country

Country Per-capita spending on prescription drugs, 2014 USD[29]
United States 1112.2
Canada 772.2
Germany 741.1
Switzerland 730.4
Ireland 703.4
France 655.9
Greece 629.6
Belgium 623.0
Austria 609.2
Spain 546.9
Italy 544.2
Hungary 543.2
Slovak Republic 532.6
Iceland 490.3
Sweden 488.7
Korea 487.4
United Kingdom 485.3
Slovenia 483.5
Lithuania 479.1
Finland 476.0
Norway 457.4
Czech Republic 408.3
Netherlands 400.7
Portugal 398.6
Luxembourg 377.4
Latvia 347.6
Poland 339.0
Denmark 324.6
Estonia 324.4
Russia 317.5
Mexico 279.1

Techniques for individuals to reduce costs

Pill splitting

Many pill-form drugs are produced in several different dosages. For example, a medicine may be prescribed at a 25 mg or a 50 mg dose. Some medicines can be prescribed at a higher dose and then the tablets can be split into two or more parts. High-dose pill are often much cheaper per unit weight than their low-dose counterparts. Not all pills can be split, since some come as time release capsules or require very precise dosing.

Generic drugs

Generic drugs are much less expensive than brand-name drugs. Many people think that generics are less effective or less safe than a brand name drug, but this is an error. Once a drug is developed, it is protected by patent and sold as a brand name drug for several years, and can be sold as a generic drug or under a different brand when the patent expires.

90-day supply

Some drugs are available in a three-month supply at a lower unit cost than a smaller supply.

Stopping medicines that may no longer be needed

Taking a prescription medicine may become so routine that patients continue to take it even when it is no longer necessary. However, many medicines may not be needed indefinitely.

Buying from cheaper supplier

Different suppliers may have different prices. There are several government and commercial websites that will compare the prices for a given dosage of a given medication at different pharmacies.

Target followed suit in some locations soon after Wal-Mart. Many other chains have followed their lead, including CVS and Sams Club(owned by walmart). Most chains in the USA now offer some sort of discount plan. This is usually in the form of a special price list, a loyalty discount program, or price matching of other competitors schemes. Prescription pricing has become extremely competitive, with such discounts often resulting in a charge lower than the copay through a patients insurance.

Counterfeit medications

There are many counterfeit medicines on the market, posing as both generic and proprietary brands. The counterfeits may be less effective than the real drug, or may have no active ingredients at all. This is a particular problem in countries with poor supervision of the pharmaceutical sector, which often also have many inhabitants with low incomes. Medicines bought over the Internet are also often found to be counterfeit. This can make saving on prescription costs risky.

Research regarding out-of-pocket prescription costs

While there are many mechanisms for reducing out-of-pocket prescription costs, pharmaceutical samples actually do not reduce prescription costs. Even after receiving samples, sample recipients remain disproportionately burdened by prescription costs.[30]

For many drugs, especially brand-name antihypertensive fixed-dose medications, the clinical benefits must be balanced with patient financial burden and nonadherence during prescribing.[31]

A study has been done on the cost effectiveness of purchasing a three-month supply, which finds that there is a quantitative cost difference when patients in the U.S. fill larger quantities of a prescription drug for a chronic condition.[32]

Another way to perhaps reduce out-of-pocket costs is to improve physicians' access to health information technology. While physicians with high rates of IT use do not have significantly higher knowledge of drug costs, it has been suggested that health IT should be improved to make it easier for physicians to access cost information at the point of care.[33]

See also

References

  1. ↑ The Editorial Board (19 December 2015). "No Justification for High Drug Prices". New York Times. Retrieved 20 December 2015.
  2. ↑ International Federation of Health Plans.
  3. 1 2 3 4 5 LaMattina, John. "What Is The Rationale For The Pricing Of New Drugs?". Forbes. Retrieved 2016-03-15.
  4. ↑ Al-Huniti, Nidal (June 20, 2013). "Quantitative Decision-Makingin Drug Development". AstraZeneca. p. 23. Retrieved March 13, 2016.
  5. ↑ Klotz, Lynn (January 16, 2014). "What Is the Real Drug Development Cost for Very Small Biotech Companies?". Genetic Engineering & Biotechnology News. Retrieved March 15, 2016.
  6. 1 2 3 4 5 6 "New Drug Development Process" (PDF). California Biomedical Research Association. Retrieved March 15, 2016.
  7. 1 2 Herper, Matthew. "The Truly Staggering Cost Of Inventing New Drugs". Forbes. Retrieved 2016-03-15.
  8. ↑ Gaffney, Alexander. "FDA Publishes All User Fee Rates for Fiscal Year 2014 | RAPS". www.raps.org. Retrieved 2016-03-15.
  9. ↑ "LIPITOR (atorvastatin calcium) Side Effects | Safety Info". LIPITOR. Retrieved 2016-03-15.
  10. ↑ Bliss, Susan J. "Simvastatin vs. Atorvastatin: What You Should Know". Healthline. Retrieved 2016-03-17.
  11. 1 2 Calo-Fernández, Bruno; Martínez-Hurtado, Juan Leonardo (2012-12-12). "Biosimilars: Company Strategies to Capture Value from the Biologics Market". Pharmaceuticals. 5 (12): 1393–1408. doi:10.3390/ph5121393. PMC 3816668Freely accessible. PMID 24281342.
  12. ↑ "Good vs. Bad Cholesterol". www.heart.org. Retrieved 2016-03-16.
  13. ↑ The 2012 Pfizer Annual Financial Report
  14. ↑ Prescription Assistance - Database of patient assistance programs
  15. ↑ For example: Campath
  16. ↑ Drug Companies Really Don’t Care About the Price Hike Backlash
  17. ↑ Martin Shkreli-style drug price hikes are everywhere
  18. ↑ FDA Works to Lessen Drug Shortage Impact
  19. ↑ MSF Access Campaign
  20. ↑ Sanghoee, Sanjay. "The Unintended Side Effect of Lower Drug Prices". TIME.com. Retrieved 2016-03-15.
  21. 1 2 3 4 "CEO says he'll lower price of drug after public outcry over 5,000% price hike". www.cbc.ca. September 23, 2015. Retrieved 2016-03-16.
  22. ↑ Prescription Drug Costs: Background Brief – KaiserEDU.org, Health Policy Education from the Henry J. Kaiser Family Foundation. Kaiseredu.org. Retrieved on 23 April 2011.
  23. ↑ Zullo, Andrew R.; Dore, David D.; Galárraga, Omar (March 2015). "Development and validation of an index to predict personal prescription drug importation by adults in the United States". Journal of Pharmaceutical Health Services Research. 6 (1): 33–41. doi:10.1111/jphs.12088. Retrieved 27 July 2015.
  24. ↑ Zullo, Andrew R.; Dore, David D.; Galárraga, Omar (March 2015). "Development and validation of an index to predict personal prescription drug importation by adults in the United States". Journal of Pharmaceutical Health Services Research. 6 (1): 33–41. doi:10.1111/jphs.12088. Retrieved 27 July 2015.
  25. ↑ A quick guide to help with health costs including charges and optical voucher values, Effective from 1 April 2008, NHS
  26. ↑ Angela Saini Making poor nations pay for drugs, New Scientist, 31 March 2007
  27. ↑ GSK tops new ethical ranking for investors – health – 16 June 2008. New Scientist. Retrieved on 23 April 2011.
  28. ↑ Drugs bust – 13 June 2001. New Scientist. Retrieved on 23 April 2011.
  29. ↑ OECD Data / Pharmaceutical spending
  30. ↑ Alexander, G Caleb; Zhang, James; Basu, Anirban (2008). "Characteristics of Patients Receiving Pharmaceutical Samples and Association Between Sample Receipt and Out-of-Pocket Prescription Costs". Medical Care. 46 (4): 394–402. doi:10.1097/MLR.0b013e3181618ee0. PMID 18362819.
  31. ↑ Rabbani, Atonu; Alexander, G. Caleb (2008). "Out-of-pocket and Total Costs of Fixed-dose Combination Antihypertensives and Their Components". American Journal of Hypertension. 21 (5): 509–13. doi:10.1038/ajh.2008.31. PMID 18437141.
  32. ↑ Rabbani, A; Alexander, GC (2009). "Cost Savings Associated with Filling a 3-Month Supply of Prescription Medicines". Applied Health Economics and Health Policy. 7 (4): 255–64. doi:10.2165/11313610-000000000-00000 (inactive 1 February 2015). PMID 19905039.
  33. ↑ Tseng, CW; Brook, RH; Alexander, GC; Hixon, AL; Keeler, EB; Mangione, CM; Chen, R; Jackson, EA; Dudley, RA (2010). "Health information technology and physicians' knowledge of drug costs". The American journal of managed care. 16 (4): e105–10. PMID 20370310.

Further information

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