New Push Ties Cost of Drugs to How Well They Work

Source: Wall Street Journal

As drug costs rise, Express Scripts seeks new payment deals for some cancer medications

Tarceva has shown a smaller benefit in pancreatic cancer than in lung cancer.ENLARGE
Tarceva has shown a smaller benefit in pancreatic cancer than in lung cancer. PHOTO: JB REED/BLOOMBERG NEWS

Express Scripts Holding Co., a large manager of prescription-drug benefits for U.S. employers and insurers, is seeking deals with pharmaceutical companies that would set pricing for some cancer drugs based on how well they work.

The effort is part of a growing push for so-called pay-for-performance deals amid complaints about the rising price of medications, some of which cost more than $100,000 per patient a year.

Some insurers and prescription-benefit managers are pushing back by arguing that they should pay less when drugs don’t work well in certain patients. Drug companies are countering with pricing models of their own, such as offering free doses during a trial period.

Express Scripts this month told clients it is seeking deals with drug makers for differentiated pricing for certain cancer drugs based on how well they work against different types of tumors, Express Scripts Chief Medical Officer Steve Miller said in an interview. Currently, Express Scripts and most insurers pay the same per-unit rate for a cancer drug regardless of the type of cancer it is being used to treat.

Dr. Miller pointed to Tarceva, a drug co-marketed by Roche Holding AG and Astellas Pharma Inc., which has shown a smaller benefit in pancreatic cancer than in lung cancer. In one clinical trial, Tarceva extended the median survival of pancreatic cancer patients by less than two weeks versus placebo. In a separate trial, it prolonged survival among lung cancer patients by about 3 ½ months versus chemotherapy.

In an “indication-specific pricing” model, the per-pill cost of Tarceva would be lower for pancreatic-cancer patients than for lung-cancer patients, given the reduced efficacy, Dr. Miller said. Tarceva currently costs about $6,850 a month per patient, according to GoodRx, a website that tracks drug prices.

“One of the big frustrations has always been people paying top dollar for drugs that aren’t always giving them the best response,” Dr. Miller said. “If pharma is truly sincere about wanting value-based reimbursement, we now have the sophistication to do that.”


Although Dr. Miller used Tarceva as an example, he wouldn’t identify the drugs for which Express Scripts is seeking indication-specific pricing. The company has begun approaching drug makers about arranging such deals, which could go into effect for 2016, he said.

A spokeswoman for Roche’s Genentech unit said that when Tarceva was approved to treat pancreatic cancer in 2005, it was the first medicine approved for the disease in more than a decade. She said the drug is now rarely used to treat pancreatic cancer because other drugs have since been approved for the disease. She said Genentech would welcome a system of pricing a medicine based on how it performs in different indications—and has one in place in Italy—but there are challenges to doing so in the U.S., including fragmented patient-record systems.

Express Scripts has in recent years been a vocal critic of high drug prices, which the company has used to promote its services to potential customers as it competes against CVS Health Corp. and others to administer drug benefits for health insurers and large employers. Pharmacy-benefit managers also sometimes keep a portion of the rebates and discounts they negotiate from pharmaceutical companies.

Express Scripts’ approach would be similar to that proposed by Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center.

In an article published last year in the Journal of the American Medical Association, he suggested that in an indication-specific arrangement, the monthly price for Eli Lilly & Co.’s cancer drug Erbitux would plummet from $10,320 a patient to about $470 a patient for its least effective use, treating recurrent or metastatic head and neck cancer. The drug also is used to treat locally advanced head and neck cancer, as well as colorectal cancer.

A Lilly spokeswoman said Lilly supports efforts to make cancer drug reimbursement “better reflect treatment value for different patient populations,” and it is “exploring alternative options to accurately represent the value our medicines offer across multiple indications.”

Drug pricing has been “very hard for the payers to do anything about,” said Steven Pearson, president of the Institute for Clinical and Economic Review, a Boston nonprofit that evaluates cost-effectiveness in medicine. “Now they’re starting to think very hard about it, to look for practical ways to have more of an influence on pricing.”

It can be difficult for drug companies and payers to agree on terms of alternative payment deals—and to actually administer the deals.

Pay-for-performance contracts often involve tracking certain health measures and outcomes in specific patients, such as changes in blood-sugar levels for diabetes patients. The cost and complexity of such tracking can offset the benefits, and the number of such deals in the U.S. to date has been relatively small.

“They’re very data intensive to administer and track these,” says Larry Blandford, executive vice president and managing partner at Precision for Medicine, a consulting firm advising drug makers on dealing with payers.

U.S. insurers and pharmacy-benefit managers also push for simple price cuts, and sometimes win them in the form of rebates paid by manufacturers. But drug makers have been able to avoid big, across-the-board price cuts in the U.S. because the market is so fragmented, with multiple public and private payers, and because rebate contracts are typically confidential. That allows drug companies to minimize or avoid discounting certain drugs for some payers.

Some drug companies have explored their own variations of alternative pricing, such as annuity-style payments for very expensive drugs. This involves an upfront payment and then ongoing payments stretched out over several years based on how well the drug works in individual patients.

One example is Bluebird Bio Inc., which is developing an experimental gene therapy for rare diseases. At a health-care conference in February, Chief Executive Nick Leschly said that if the therapy makes it to market, he would consider asking insurers to make an upfront payment to cover costs and risk of development, plus additional ongoing payments if it works for a patient.

Other drug makers are trying different models. Since 2011, Acorda Therapeutics Inc. has provided its drug Ampyra, which can help multiple-sclerosis patients improve their walking, free for the first two months.

The reason: Studies have shown it only works in about 40% of patients, but there is no way to predict before starting therapy who will benefit. The two-months free program gives patients time to figure out if the drug is working—they usually know within several weeks, says Acorda Chief Executive Ron Cohen. If the drug works, the company begins charging the regular price, or about $21,000 a year per patient.

Acorda implemented the two-months free policy partly because some insurers were restricting its use. The two-months free program isn’t part of any contracts with insurers, but Dr. Cohen believes it sows goodwill among doctors and insurers.

“We saw that as a risk-sharing arrangement,” said Dr. Cohen.

He says “a significantly wider swath” of the drug industry is exploring alternative-pricing models than in the past. “A lot of the pressure emerges simply from the ongoing issues around the increasing cost of medicine,” he says.

Alnylam Pharmaceuticals Inc. would consider performance-based pricing if its experimental rare-disease drugs reach the market, CEO John Maraganore said in an interview. The company’s lead drug in development is a treatment for a rare disease called TTR-mediated amyloidosis. Regulators haven’t yet approved the drug for sale and Alnylam hasn’t set a price.

Mr. Maraganore said blood tests can measure the effectiveness of its experimental drug. “I think there are many opportunities for our medicines to be evaluated and potentially reimbursed on a performance basis,” he said. “We certainly would be open to that type of approach.”

The drug industry has made various stabs at alternative-pricing before. Several European state-run health systems have implemented pay-for-performance and indication-specific pricing arrangements with drug makers over the past decade. In the U.S., health insurer Cigna Corp. has signed deals that tie reimbursement for EMD Serono’s MS drug Rebif and Merck & Co.’s diabetes drug Januvia to certain patient outcomes.

Write to Peter Loftus at

SGLT2 inhibitors: Drug Safety Communication – FDA Warns Medicines May Result in a Serious Condition of Too Much Acid in the Blood

English: The blue circle is the global symbol ...
English: The blue circle is the global symbol for diabetes, introduced by the International Diabetes Federation with the aim of giving diabetes a common identity, supporting existing efforts to raise awareness of diabetes and placing the diabetes epidemic firmly in the public spotlight. (Photo credit: Wikipedia)


ISSUE: FDA is warning that the type 2 diabetes medicines canagliflozin, dapagliflozin, and empagliflozin may lead to ketoacidosis, a serious condition where the body produces high levels of blood acids called ketones that may require hospitalization. FDA is continuing to investigate this safety issue and will determine whether changes are needed in the prescribing information for this class of drugs, called sodium-glucose cotransporter-2 (SGLT2) inhibitors.


BACKGROUND: SGLT2 inhibitors are a class of prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. When untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. SGLT2 inhibitors lower blood sugar by causing the kidneys to remove sugar from the body through the urine.


These medicines are available as single-ingredient products and also in combination with other diabetes medicines such as metformin.


RECOMMENDATION: Patients should pay close attention for any signs of ketoacidosis and seek medical attention immediately if they experience symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness. Do not stop or change  your diabetes medicines without first talking to your prescriber.


Health care professionals should evaluate for the presence of acidosis, including ketoacidosis, in patients experiencing these signs or symptoms; discontinue SGLT2 inhibitors if acidosis is confirmed; and take appropriate measures to correct the acidosis and monitor sugar levels. See the FDA Drug Safety Communication for more information.


Cheap blindness drug should be made widely available, says WHO

Source: The Guardian (UK)

World Health Organisation rejects expensive licensed drug Lucentis to be added to list for all countries in favour of much cheaper Avastin, not yet available in UK

Avastin, primarily a bowel cancer drug, is similar to Lucentis but 40 times cheaper when split into tiny doses to be injected in the eye. Photograph: Bloomberg/Getty Images

All countries should make available a cheap, unlicensed drug to prevent blindness in older people – one in preference to the expensive licensed version promoted by pharmaceutical companies, a World Health Organisation committee has ruled.

The WHO’s essential medicines committee has rejected an application from Novartis to have the expensive licensed drug Lucentis added to the list of drugs all countries should stock (PDF). The decision is a blow for the pharmaceutical companies that have been fighting the growing use of Avastin for age-related wet macular degeneration. Avastin, primarily a bowel cancer drug, is similar to Lucentis but 40 times cheaper when split into the tiny doses to be injected in the eye.

The decision will bolster the case of those, like the NHS clinical commissioners, who are pressing for Avastin to be widely available in the UK, potentially saving the health service millions of pounds a year. The two drugs are made by the same company, Genentech, owned by the Swiss giant Roche, which has declined to seek a licence for Avastin to prevent blindness. Novartis markets Lucentis in Europe.

Critics accuse the companies of blocking access to a cheap drug that could slow or prevent blindness in millions of people around the world. Around 40,000 people a year develop wet AMD in the UK, according to the Macular Society. The potential NHS bill for Lucentis is huge. A head-to-head trial called IVAN, which was funded by the UK government, found that two years of Lucentis treatment cost over £18,500 compared with £3,000 for Avastin.

IVAN found the drugs work equally well, but because it does not have a licence for use in eyes, Avastin can only be prescribed by individual doctors prepared to do it on their own responsibility.

In 2013, the WHO put Avastin for macular degeneration on its list of essential medicines that every country should be able to offer its people. Novartis then requested Lucentis be considered for inclusion. But the WHO has declined. The latest edition of the essential medicines list, just published, includes Avastin (generic name bevacizumab) but not Lucentis (ranibizumab).

Nicola Magrini of the Essential Medicines List secretariat at the WHO said the committee’s decision was unanimous, after two reviews of the evidence on the drugs.

Prof John Harris, director of the Institute for Science, Ethics and Innovation at the University of Manchester said the WHO committee had made the right decision.

“Research has demonstrated that Avastin is as effective and as safe as Lucentis but at a fraction of the cost – there can be no justification for listing the more expensive and no better alternative.

“Novartis are wasting their money and patient’s and public money, and risking the sight of many patients who cannot afford Lucentis, by attempting to market Lucentis as an alternative to Avastin when there is no significant clinical advantage to patients.”

Julie Wood, director of the NHS Clinical Commissioners – the membership organisation of the groups across the country that commission healthcare – said it was helpful to their case that Avastin and not Lucentis was on the WHO essential medicines list.

“We’re trying to overcome some of the barriers that are around,” she said. That included advice from the General Medical Council that if there are two drugs that are equally effective, doctors should prescribe the licensed one.

The commissioners were most persuaded by the recent independent Cochrane review of the evidence for the two drugs, which said Lucentis was not superior. “That was a bit of a sea change for us,” she said. “That was a Cochrane review, independent of everything else, concluding that Avastin is of comparable efficacy and safety. From our point of view, that is good enough.”

Nice, the National Institute for Health and Care Excellence, which recommends which treatments the NHS should use, cannot appraise an unlicensed medicine unless the Department of Health asks it to do so. It can, however, recommend which drugs should be used in a treatment guideline – and it is now preparing one on macular degeneration.

Nuevos medicamentos para la hepatitis C, ¿valen lo que cuestan? (I: Análisis)


por PEDRO REY BIEL el 27/01/2015

De Pedro Rey Biel y Javier Rey del Castillo

hepatitis c imageLa industria farmacéutica es el principal inductor del aumento descontrolado del gasto sanitario en la mayoría de los países desarrollados, lo que se debe fundamentalmente a la introducción de nuevos medicamentos en el mercado, de precio cada vez mayor . Esta tendencia se había moderado en los últimos años, por agotamiento del desarrollo de nuevos productos por síntesis química, pero los nuevos productos biotecnológicos la han reactivado.

Gracias a los altos ingresos y a las asimetrías de información, los laboratorios farmacéuticos tienen amplia capacidad de inducir la demanda de sus productos mediante su influencia sobreprescriptores pacientes. Esta influencia se extiende también sobre quienes deben autorizar y financiar su prescripción y consumo, a precios en cuya fijación los laboratorios tratan ante todo de evitar la capacidad de negociación de los consumidores colectivos más importantes, como son los servicios públicos de salud.

Por otra parte, ante la extrema dificultad de conocer de forma no sesgada los verdaderos costes asociados a la investigación y el desarrollo de los nuevos productos, en especial los biotecnológicos, existe amplio consenso en considerar que la causa principal de su elevado precio es la escasez de competencia en el momento en que sale el primer medicamento para cualquier enfermedad que, debido al fuerte sistema de protección de patentes, influencia de forma clara la evolución de los precios de productos similares y derivados cuando aumentan las condiciones de competencia.

Ambos factores han contribuido a la actual “crisis” desencadenada por la utilización de un nuevo fármaco, caro pero efectivo contra la hepatitis C, el sofosbuvir (Sovaldi):

– Como se ha publicitado extensamente, Gilead, el laboratorio que comercializa el medicamento que centra la polémica, no participó de forma activa en su investigación ni, por tanto, en sus costes de desarrollo, y se limitó simplemente a anticipar las posibilidades de negocio y comprar los derechos de patente a Pharmaset (en el que participaba Roche) a un precio de alrededor de 11.000 millones de dólares (8.000 millones de euros. Sin embargo, ese precio se considera ahora bajo en relación con las perspectivas de negocio que sugieren los 1.100 millones de euros conseguidos por Gilead en el primer año de comercialización del producto, aún en condiciones de uso limitado en la mayoría de los países que lo han autorizado, a precios muy elevados (62.000 euros por tratamiento de 12 semanas en los Estados Unidos; 55.000 en Francia).

– Los altos precios del medicamento impuestos en todos los países son una muestra de hasta qué punto se puede descontrolar el gasto de los servicios sanitarios, ya comprometido, si en la formulación de la demanda (inducida), determinada por las indicaciones del uso del  producto, y en la fijación de los precios, el poder de monopolio del laboratorio productor se impone al (potencial) poder monopsonista de quien sea en cada caso el principal comprador, sea el servicio público de países como el Reino Unido, Francia o Alemania, o privado, como es el caso de las aseguradoras privadas norteamericanas .

Unos y otros han reaccionado de maneras diferentes para afrontar el problema: desde una delimitación de las indicaciones de uso del tratamiento, como ha ocurrido en Francia, al intento de introducir mecanismos de competencia que hagan que el precio se reduzca. Ejemplos de esto último son los convenios de uso exclusivo de nuevos medicamentos de eficacia curativa similar a la del sofosbuvir, ya autorizados y a punto de lanzarse al mercado, firmados por algunas aseguradoras americanas con los laboratorios correspondientes . Una actitud similar parece subyacer al acuerdo adoptado hace pocos días por el NHS británico para demorar hasta el mes de julio la autorización del uso del producto, que, tras los informes del NICE (National Institute of Clinical Excellence, su agencia de evaluación tecnológica), estaba previsto comenzar a utilizarse en abril .

Sin embargo, en el caso de España, a estos factores generales se han añadido algunos específicos, que han hecho que la “crisis” haya alcanzado aquí una relevancia pública mayor:

1) La extensión de la enfermedad: a falta de datos oficiales consolidados, la prevalencia de la hepatitis C en los países del Sur de Europa parece mucho mayor (del 0,5% de la población en países escandinavos al 5% en países mediterráneos). En España se estima que hay hasta unos 300.00 afectados “reconocidos” (cifra que podría alcanzar los 900.000 si se incluyen los portadores no detectados), para una población de alrededor de 46 millones de habitantes, mientras que en Francia, donde el número de afectados ronda los 200.000 para una población total de alrededor de 70 millones.

2) El mecanismo de fijación de los precios de los medicamentos. Esta función corresponde en España a una Comisión Interministerial presidida por el Mº de Sanidad, de la que también forman parte los Mºs de Hacienda e Industria, cuyos objetivos recaudatorios y de desarrollo de determinados sectores industriales pueden diferir de los sanitarios.  Sin embargo, dicha Comisión fija los precios para su uso por el Sistema Nacional de Salud (SNS), que no participa directamente en la negociación.

En la inclusión de medicamentos en la financiación del SNS y la determinación de los precios para el uso de los mismos en este ámbito, la Ley 29/2006, de 26 de julio,  en distintos artículos (89, 89 bis, y 90)  de su redacción actual, dice que la Comisión debe tener en cuenta distintos criterios sanitarios y no sanitarios, incluidas valoraciones de su coste-efectividad e impacto presupuestario, antes de fijar el precio “de manera motivada y conforme a criterios objetivos“, sin cuya fijación no es posible su prescripción en el SNS. 

La reiteración legal de la necesidad de justificar las razones que han llevado a establecer el precio fijado para el uso de cada medicamento por el SNS, no se acompaña, sin embargo, del establecimiento legal de una obligación taxativa de hacer pública la justificación mencionada, de manera que el precio fijado pudiera ser recurrible en su caso por quien se pudiera ver afectado por el mismo en sus intereses. La ausencia de una clausula legal que lo establezca así se ha venido acompañando, por el contrario, de una práctica sistemática en la que el conocimiento del precio, siquiera el industrial de referencia, se oculta, o se dificulta sistemáticamente, en especial en el caso de los medicamentos de uso hospitalario. Por otra parte, los precios industriales  tienen el carácter de “máximos”, y no tienen por qué ser los aplicables  por igual en todas las instituciones y servicios, que tampoco son conocidos públicamente. La existencia de diferentes sistemas de compra descentralizados facilita, por el contrario, que el precio real aplicado a instituciones y servicios distintos del SNS responda a las políticas de precios diferenciales que más convenga a los intereses del laboratorio implicado.

Esta manera de actuar, que se ha mantenido en equilibrio aparente hasta la fijación del precio del Sovaldi,  sin que ni los laboratorios ni la Administración la hayan puesto en cuestión, dista mucho de ser una negociación en la que un comprador, el SNS, pueda ejercer su poder monopsonista para negociar un precio bajo. Aunque en apariencia la fijación de precios unilateral por parte del comprador le daría aún más poder de mercado, en la práctica la falta de trasparencia en el proceso, y la descentralización de los sistema de compra, provoca que el regulador se adapte en gran medida a las demandas de los laboratorios, que ejercen presión a través de asociaciones de pacientes y de médicos, informados de forma obviamente interesada, sobre la benevolencia y novedad de sus medicamentos.

En el caso del Sovaldi, la reciente creación de una nueva comisión, dependiente únicamente del Mº de Sanidad, para analizar los aspectos epidemiológicos y clínicos de la enfermedad, y proponer las medidas de utilización más adecuada del producto desde el punto de vista médico, confirma que su labor en este caso, que legalmente debería haber correspondido a la Comisión Interministerial antes de la fijación del precio, no se ha cumplido, sin que, como se ha indicado, existan siquiera vías establecidas para recurrir el acuerdo que se haya adoptado; el mismo puede , sin embargo, ser revocado por el propio órgano, la Comisión Interministerial que lo ha adoptó. Como consecuencia, hasta el momento, el precio “máximo” que parece se ha fijado (25.000 euros por tratamiento de 12 semanas) es muy elevado.

3) La demora en la fijación del precio ha tenido efectos secundarios muy importantes en la manifestación y la extensión del problema ante la opinión pública.

La autorización del medicamento por la Agencia europea (EMA) se produjo en noviembre de 2013, aunque la fijación del precio para el SNS no parece haberse hecho hasta un año después. A su vez, el Mº de Sanidad hizo pública la previsión de los pacientes a los que se podría aplicar en función del precio y el presupuesto disponible fijados, y no a la inversa. El criterio era el de incluir a los pacientes afectados en fases más avanzadas (fase 4 descompensada ), de manera aún más restrictiva que en otros países (que incluyen la fase 4 no descompensada) hasta un total de entre 5.000 y 6.000.

Durante el año trascurrido entre autorización y fijación de precio, el conocimiento por parte de los profesionales médicos de la existencia de un producto más eficaz para el tratamiento de la infección que los disponibles, sin que, sin embargo, fuera posible su uso por no estar establecido su precio,  creó suspicacias frente al Mº de Sanidad. Esas razones llevaron finalmente a que, cuando el Mº hizo públicas las pautas de uso indicadas adaptadas al precio fijado, estas fueran contestadas mediante un comunicado un tanto insólito de la Asociación Española de Estudio del Hígado, invitando expresamente a que los profesionales del SNS no siguieran las pautas indicadas.

Son esos fundamentos los que dieron lugar a la protesta de distintas asociaciones de pacientes, que, de manera comprensible pero no necesariamente compartida, demandan el uso inmediato y generalizado del producto, sin referencias a las indicaciones en que se debería utilizar, ni  al precio aplicable para su utilización .

Pero no sólo es peculiar la situación de la “crisis” en España. También lo son las propuestas que se están planteando para su solución desde distintos ámbitos. Como ya nos estamos extendiendo, esta tarde, en una segunda entrada, discutiremos las posibles soluciones.

Enlaces de interes: y

(BMJ 2015; 350 doi:

– Stop Subsidizing Big Pharma:
– El número de 13 de enero de la revista JAMA está dedicado a este tema:

Terapia antitrombótica

Via: Galo Sanchez

Las guías clínicas de la Sociedad europea de cardiología, en 2011, y de la American Heart Association, en 2009, aconsejan que todas las personas que han padecido un IAM reciban terapia antitrombótica con aspirina y clopidogrel durante 12 meses, y un agente de los dos para continuar. Además, una proporción de pacientes requerirá luego terapia con anticoagulantes orales. Ciertos agentes (por ejemplo Ibuprofeno) pueden impedir los efectos antitrombóticos de la aspirina. Los AINEs pueden no sólo aumentar el riesgo de hemorragia, sino también el riesgo de sufrir eventos cardiovasculares. A pesar del amplio uso de AINEs en la población, no se ha evaluado la seguridad de la adición un AINE a las diferentes combinaciones de medicaciones antitrombóticas después de IAM. Y para investigarlo, Carter y col diseñaron y llevaron a cabo un Estudio de Cohortes Retrospectivo (que constituye la mejor evidencia disponible en la seguridad en este asunto).


Por el interés que tiene para la seguridad de un gran número de pacientes actualmente, Martha Hack[1] ha hecho una evaluación GRADE de este estudio, cuyo resultado hemos puesto a disposición de los lectores en, pestaña FORMACIÓN, aunque puede verse directamente en:

[1] Martha Hack. R-4 Medicina de Familia. Centro de Salud Zona Norte, Cáceres.

Safety Patients: Olmesartan

  • Fda
    Fda (Photo credit: Wikipedia)

    Olmesartan: Drug Safety Communication – FDA Review Finds Cardiovascular Risks for Diabetics Not Conclusive

    Includes: Benicar, Benicar HCT, Azor, Tribenzor, and Generics

    AUDIENCE: Cardiology, Pharmacy, Family Practice, Endocrinology

    ISSUE: FDA has completed its safety review and has found no clear evidence of increased cardiovascular risks associated with use of the blood pressure medication olmesartan in diabetic patients (see previous alerts linked below). FDA believes the benefits of olmesartan in patients with high blood pressure continue to outweigh the potential risks.

    BACKGROUND: FDA safety review was prompted by the results of the ROADMAP trial. The ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) clinical trial examined the effects of olmesartan in patients with type 2 diabetes, to see whether olmesartan could delay kidney damage. There was an unexpected finding of increased risk of cardiovascular death in the olmesartan group compared to the group taking a placebo, or sugar pill. However, the risk of non-fatal heart attack was lower in the olmesartan-treated patients. To evaluate these findings, FDA reviewed additional studies, including a large study in Medicare patients.