Target Health Presenting at DIA Annual Meeting (Boston) on eSource
Target Health Inc. is pleased to announce that Dr. Jules T. Mitchel will be presenting a talk as part of the “eSource Symposium,” which will take place at the annual meeting of the Drug Information Association (DIA), which is being held in Boston this year (June 23-27, 2013). This symposium is part of the Innovative Approaches to Ensuring Compliance with Good Clinical Practice (GCP) and Quality Assurance (QA) track.
The symposium will take place on June 27, between 9:00AM – 10:30AM, and will be chaired by our colleague Patricia Beers Block. Pat spent 32 years with the U.S. Food and Drug Administration and was recently Vice President of Strategic Regulatory Initiatives, at Medidata Solutions.
This symposium will introduce risk-based approaches when electronic data are intended to serve as the source of clinical data. Additionally, we will discuss how monitors and data managers can work together when developing and implementing a risk-based monitoring program. A final topic is the assessment of electronic health record systems that will be the repository of eSource data.
Learning objective are 1) understand the principles of risk-based approaches to successfully using eSource clinical data; 2) identify how to implement a risk-based study monitoring approach to electronic clinical data; 3) describe methods to successfully assess electronic health records systems that will be used for clinical data.
A Common Tool for Investigator Site eSource (EHRS) Readiness Assessment – Patricia Beers Block
eSource and Risk-Based Monitoring: Impact on Sites, Data Management and Regulatory Compliance – Edward Stephen Seguine, CEO, Clinical Ink
Is It Time to Change the Clinical Trial Monitoring Paradigm? Results From a Phase 3 Clinical Trial Using EDC Fully Integrated With the eClinical Trial Record for Real-time Data Entry (eSource), Together with Risk-based Monitoring – Jules T. Mitchel, President, Target Health Inc.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com
Civil War Medicine with a Focus on Missouri
Civil War Amputation Kit Image courtesy of the Civil War Museum at Wilson’s Creek National Battlefield
The medical establishments within the U.S. Army and the nascent Confederate Army were almost totally unprepared for either the scope or duration of the American Civil War. The peacetime U.S. Army had only 113 physicians to care for more than 16,000 personnel scattered across the country. The Army’s Surgeon General, Dr. Thomas Lawson, was unable to think beyond the needs of small, frontier post hospitals. Fortunately for the Union, the Medical Department entered a new era under a relatively junior physician, Dr. William A. Hammond, on April 25, 1862. The Confederate Medical department had to begin from scratch.
Contrary to popular belief, nineteenth century 1) ___ was not always crude and ineffective. Lack of preparedness was the foremost problem, and it was responsible for much otherwise unnecessary suffering. The Civil War brought important advances in both organization and technique. While shortages often crippled the Confederacy’s efforts, by the end of the conflict the medical treatment available to Union soldiers was probably the best in the world. It gave sick and injured 2) ___ a greater opportunity of recovery than in any previous war.
With the outbreak of war civilian doctors entered the ranks of the Northern and Southern forces in large numbers. While some had served only an apprenticeship with an experienced practicing physician, formal medical education was becoming common. Diploma mills existed, but so did an increasing number of respected medical 3) ___, such as the McDowell Medical College in St. Louis. By modern standards the curriculum in even the best schools was surprisingly brief lasting two years, with the second year being merely a repeat of the first. Not surprisingly, the quality of military surgeons differed considerably. Late in 1861 the U.S. Army Medical Department began giving examinations to weed out unqualified physicians. The Confederacy soon took similar and perhaps even more rigorous steps.
Education and peacetime practice did little to prepare 4) ___ to treat the mass casualties of war.
Missouri, being a divided state, had two governments during the Civil War.
The border troubles labeled “Bleeding Kansas” in the Eastern press gave Missouri a reputation for violence, yet prior to the Civil War relatively few physician within the state ever treated a gunshot wound or performed more than minor surgery, much less attempted the amputation of a limb. The same was true elsewhere. Moreover, once in uniform, few military surgeons considered it to be their duty to address the basic requirements to keep the men healthy to fight, such as proper sanitation, food, and shelter. Civilian organizations, often labeled “sanitary commissions,” sprang up to address these needs, but in Missouri the dynamics of the conflict limited these to the Union side. St. Louis became the center of the regional Western Sanitary Commission, as well as the local St. Louis Ladies Union Aid Society and parallel Colored Ladies Union Aid Society.
In Union and Confederate volunteer service, and in the Missouri State Guard, regulations authorized each regiment a surgeon, an assistant surgeon, a hospital steward with the rank of sergeant major, and several enlisted men serving as orderlies. Each morning at “sick call,” the surgeons listened to soldiers’ complaints and provided treatment. The steward was responsible for supplies and medicine chests. Orderlies were jacks-of-all-trades, men who showed an interest and aptitude in 5) ___ and were appointed by the surgeon. During combat the medical team set up a field hospital close to the action. The assistant surgeon usually manned an aid station treating wounded at the edge of the battlefield until they could be removed to the surgeon’s care at the field hospital. Near the end of 1861 the Union army began consolidating regimental hospitals into division and corps hospitals to handle larger bodies of troops more efficiently, but an Ambulance Corp was not formed until well into 1862. Prior to that wounded were brought from the field either by comrades or by musicians from the regiment’s band, if it had one.
Gunshots accounted for 94% of the recorded battle 6) ___. Injuries from artillery projectiles were less common, while bayonet and sword wounds were quite rare. The most common wounds were to the extremities, with almost equal involvement of the arms and legs. In combat involving muzzle-loading weapons, limbs often remained vulnerable even when a soldier fired from a protected position. Non-extremity wounds almost always resulted in death on the battlefield. Penetrating gunshots to the abdomen or head were about 90% fatal, those to the chest about 60%.
Contrary to myth, Civil War doctors did not perform excessive numbers of 7) ___ because they were ignorant of, or unwilling to consider, alternatives. Doctors usually performed amputations in cases involving the penetration of a joint, a compound fracture, substantial tissue or bone destruction, or evidence of infection (gangrene). They had to consider the fact that survival rates were much greater when amputations were performed within the first twenty-four hours of injury. This was called primary amputation. Secondary amputations were performed after the 24 hour period and resulted in higher mortality and morbidity caused by bacteria having more time to enter the open wound. Surgeons were aware that the presence of foreign material such as wadding, clothing fragments, or dirt in wounds increased the likelihood complications. Tragically, it was not until just after the war ended that European physician Joseph Lister, using the work of Louis Pasteur, demonstrated the role that 8) ___ played in wound infection, too late to save the lives of tens of thousands of men in uniform.
One of the war’s most important advances was the popularization of anesthesia. Military surgeons employed ether and chloroform, which had first come into use at the time of the Mexican War, 1846-1848. Both drugs had drawbacks. Highly flammable ether, which took sixteen minutes to take effect, posed a danger when operations were performed by candle or lantern light. Chloroform was nonflammable and worked in about nine minutes, but improper application could result in death. During those nine minutes the patient passed through an excitable stage and might need to be restrained. The process was poorly understood by laymen observers and led to the myth that many operations were performed without any anesthetic at all, which was rarely the case. Recovering patients received either morphine or opium, which were effective painkillers but 9) ___.
Although more than a thousand military engagements occurred in Missouri, disease killed over twice as many men as bullets. Infections spread rapidly in overcrowded camps. Measles, mumps, rubella, and chicken pox ran rampant, particularly among newly-enlisted soldiers from rural areas who lacked immunities from prior exposure. But even more fatalities resulted from dysentery and diarrhea contracted due to unsanitary conditions. The Western Sanitary Commission worked tirelessly throughout the war to improve conditions in camps, hospitals, and prisons. Science largely ignorant of the cause of diseases and most medications were ineffective. Malaria was the only major disease combated successfully, being treated with 10) ___, a drug made from the bark of the Peruvian Cinchona tree.
Physician, Major Martin R. Delany
“Once let the black man get upon his person the brass letter, U.S., let him get an eagle on his button, and a musket on his shoulder and bullets in his pocket, there is no power on earth that can deny that he has earned the right to citizenship.” – Frederick Douglass
Missouri was the first State to see Colored Troops in combat. Only men ages 18 to 45, of good health and physical condition could enlist in the U.S. Colored Troops. Before December 1863, Missouri slaves of loyal masters needed consent before enrolling. The first colored regiment organized in the State of Missouri was the 3rd Arkansas Infantry (African Descent). It was composed of primarily Missourians but because of prejudice the State did not want to claim them as their own. The unit was composed of freemen and slaves of masters loyal to the Union. They began recruitment on shortly after May 22, 1863 and were organized Aug 12, 1863 at Schofield Barracks, St. Louis, Mo. They were re-designated the 56th U.S. Colored Troops on March 11, 1864. Most of their service was garrison duty at Helena, Arkansas but they did go on two nearby expeditions. The regiment lost a whopping 674 men; 25 killed; 649 died of disease. It remained on duty at Helena till mustered out, Sept. 15, 1866. “Nearly 40,000 black soldiers died over the course of the war – 30,000 of 11) ___ or disease.”
In June 1864 Congress granted equal pay to the U.S. Colored Troops and made the action retroactive. Black soldiers received the same rations and supplies. In addition, they received comparable 12) ___ care. Colored Troops had separate hospital wards at Benton Barracks. Nurses were staffed by the Colored Ladies Union Aid Society.
Not all the troops at Benton Barracks experienced good treatment from the government. Lt. Col. William F. Fox, U.S.V. reported that for the 2nd Missouri Colored Infantry, “Over 100 men died at [Benton] Barracks before the regiment took the field, the men having been enlisted by the Provost-Marshals throughout the State and forwarded to this Post during an inclement season,– thinly clad, and many of them hatless, shoeless, and without food. Many suffered amputation of frozen feet or hands, and the 13) ___ engendered by this exposure resulted in a terrible and unprecedented mortality.” In wartime Missouri, no matter what Congress says, there were no guarantees for former slaves.
The highest ranking black was Martin R. Delany, commissioned a Major and “graduate of the Harvard Medical School and the first Negro field officer to serve in the Civil War.” He served in the 104th Regiment U.S. Colored Troops. [The New York Times, Mar.1, 1865]
Lincoln University of Missouri (Jefferson City) was founded in 1866 by officers and men of the 62nd and 65th U.S. Colored Troops.
ANSWERS: 1) military; 2) soldiers; 3) schools; 4) physicians; 5) nursing; 6) wounds; 7) amputations; 8) bacteria; 9) addictive; 10) quinine; 11) infection; 12) medical; 13) diseases
Physician, Major Martin R. Delany
African Americans in Medicine in the Civil War Era
Canadian citizen, Anderson Ruffin Abbott in a U.S. Army Uniform, 1863
Photo Image: Courtesy of the Toronto Public Library
Most Americans are now familiar with the contribution of nearly 300,000 black soldiers and sailors to the Union cause during the U.S. Civil War. Less well known is the role of a dedicated group of black doctors and nurses in uniform who worked diligently to save lives and fight disease. In 2006, retired physician Robert G. Slawson who is now with the National Museum of Civil War Medicine in Frederick, Maryland, wrote Prologue to Change: African Americans in Medicine in the Civil War Era to introduce those men and women to the public. What follows is an introduction to these medical professionals based on his research.
The involvement of African Americans in medicine in the Civil War era is an untold chapter in our history. Up to that time most practitioners had learned medicine by apprenticeship but this began to change in the early 19th Century. James McCune Smith was the first African American to obtain a medical degree when, in 1837, he was graduated from the University of Glasgow in Scotland. In 1847 David James Peck was the first to receive a medical degree in the United States. By the end of the Civil War at least 22 African Americans had obtained degrees and were practicing medicine. At least twelve of these physicians served with the Union Army. Three men were commissioned officers while the remaining nine served as acting assistant surgeons (contract physicians). Alexander Thomas Augusta from Norfolk, Virginia, was unable to obtain admittance to a United States medical school so he went to Ontario, Canada. There he was successful in gaining admittance to Trinity College, Ontario University. In 1860 he became the first person of African ancestry to receive a medical degree in Canada. He received his commission as a surgeon (with the rank of major) in April 1863 in the 7th United States Colored Infantry (known popularly by the initials, USCT, for U.S. Colored Troops). Augusta was the first African American to obtain this rank in the U. S. Army. At the end of the war he was brevetted to lieutenant colonel, a promotion for meritorious service. When Howard Medical College opened in 1868, he was the only African American on its original faculty. When Augusta died in 1890 and was the first African American officer to be buried in Arlington National Cemetery.
John van Surly DeGrasse was an 1849 graduate of Maine Medical College, affiliated with Bowdoin College. He served as an assistant surgeon (lieutenant) in 35th U.S. Colored Infantry, returning to Massachusetts to practice after the war. He died there in 1868 at age 43. David O. MCord, an 1854 graduate of the Medical College of Ohio, was a surgeon (major) in the 63rd U. S. Colored Infantry. The remaining nine men all served as acting assistant surgeons. They all served in USCT units or in the contraband hospitals. The largest of these was the Contraband Hospital in Washington, D.C. which became Freedman’s Hospital after the Civil War and later Howard Hospital as part of Howard University.
The first of these, Anderson Ruffin Abbot, was a Canadian and had worked with Dr. Augusta in Canada. He was appointed an acting assistant surgeon in 1863, prior to obtaining his degree, and worked at the Contraband Hospital in Washington during the war. He returned to Ontario, Canada, where, to supplement his medical license, he received a medical degree from the Toronto College of Medicine in 1867. Abbott practiced in Ontario until his death in 1913.
Benjamin A. Boseman, from New York, was graduated from the Maine Medical College in 1864, and served in South Carolina during the Civil War. After the war ended he remained in South Carolina and served in that state’s legislature from 1868 until 1873 when he was appointed Postmaster of Charleston, South Carolina. He served in that post until his death in 1883.
Cortland van Rensselaer Creed graduated from Yale University School of Medicine in 1857. He served with the 30th Connecticut Volunteers (USCT). Creed returned to Connecticut to practice medicine after the Civil War and subsequently became a Justice of the Peace. He died there in 1900.
William B. Ellis was an 1858 graduate of Dartmouth Medical College. Little is known about him except that he served as an acting assistant surgeon.
Before the Civil War Joseph Dennis Harris, from Virginia, wrote a book supporting colonization for African Americans and went to Haiti to promote that cause. He later decided on medicine as a career and, after one year at the Medical Department of Western Reserve College (now Western Reserve University), he served in Virginia where he stayed after the war. In 1869 Harris was a candidate for Lieutenant Governor of Virginia but did not win the election.
William R. Powell, Jr. was the son of an African American physician in New York City. He spent time in England and said that he had graduated from the College of Physicians and Surgeons in London although no record of this exists. He served at the Contraband Hospital in Washington, D.C. during the Civil War. After the war he moved to California and, in 1901, he moved to England
Charles Burleigh Purvis is the best known of this group of men. He was from a prominent abolitionist family in Philadelphia and received his degree in 1865 from the Medical Department of Western Reserve College. He was assigned to the Contraband Hospital in Washington, D. C. in the last months of the Civil War. In 1869 Purvis became the second African American physician on the faculty of Howard Medical College and stayed with that institution for 54 years, at times serving as Chief of Surgery at Howard Hospital.
John Rapier, Jr. was from Alabama and Tennessee. He traveled to Haiti and then to Jamaica where he became interested in medicine. He received his medical diploma from the Iowa College of Physicians and Surgeons in 1864. He, too, served at the Contraband Hospital in Washington, D.C., and was still in active service there when he died of “bilious fever” in 1866.
Alpheus W. Tucker from Michigan was graduated from the Iowa College of Physicians and Surgeons in 1865. He served at the Contraband Hospital in Washington, D.C. and stayed in Washington to practice medicine after the war. In 1869 he applied for membership in the District of Columbia Medical Society, with Drs. Augusta and Purvis, but all three were denied membership.
Martin Robison Delaney deserves mention here although he did not serve as a physician. He was admitted to Harvard Medical College in 1850 but, because of student unhappiness over matriculation of African American students, was only allowed to stay one year and did not obtain a degree. He previously had apprenticed as a dentist and as a physician so he did practice medicine for some time. After the Emancipation Proclamation, he worked as a recruiter for the USCT in Rhode Island and in Massachusetts. Because of his strong belief that African American soldiers should have African American officers, he sought, and ultimately obtained in March 1865, a commission as major in a USCT infantry unit but the war ended before the unit was fully activated. He was, for a time after the war, an assistant sub-commissioner in South Carolina for the Freedman’s Bureau.
Rebecca Lee, the first black woman to receive a medical degree, but did not serve with the U.S. Army during the Civil War although she was active immediately after the war ended. Lee received her medical degree in 1864 from the New England Female Medical College. After the surrender of Richmond, Virginia, to Union troops in April, 1865, she went to the city to work with volunteer agencies at the contraband camp there. She subsequently married a Dr. Crumpler and returned to Boston where she practiced for several years. In 1883 she published a self-help medical book for women (A Book of Medical Discourses).
As with the white population, many African Americans served as nursing personnel during the war in both paid and volunteer capacities. The Navy enlisted several African American women as a “first class boy” into the Navy and used them as nurses on hospital ships like the U.S.S. Red Rover. The best known of these women is Ann Bradford Stokes. She was enlisted in the Navy in January 1863 and served until October 1864 as a nurse on the Red Rover. After leaving the Navy she married Gilbert Stokes. In 1890 she applied for a disability pension for her own service and was certified by the Navy as having served on active duty in the Navy for 18 months. She was awarded this pension in 1890 and is the first woman in the United States to receive a pension for her own military service. She was also one of the first African American nurses in the United States Navy.
This summary of the African American medical experience during the American Civil War only begins the story. Undoubtedly many whose names are not yet known served in similar capacities at that time. It is hoped that this account will be the stimulus to find and report others who served so that their heroic and trend-setting actions can be celebrated.
Susie King Taylor, 1902
Courtesy East Carolina University
Susie King Taylor’s memoirs are the only known published recollection of the experiences of an African American nurse during the Civil War. In a letter to Taylor, reproduced in her book, Lt. Colonel Trowbridge, commander of the regiment, praises her “unselfish devotion and service through more than three long years of war in which the 33d Regiment bore a conspicuous part in the great conflict for human liberty and the restoration of the Union.”
The U.S.S. Red Rover, a converted former Confederate paddle steamer became the first U.S. Naval hospital. During the Civil War, nearly 3000 patients were treated onboard
U.S.S. Red Rover, Harper’s Weekly, May 9, 1863; U.S.S. Red Rover, 1863 Courtesy National Library of Medicine
A Genome-Wide Association (GWAS) Study of Hypertension and Blood Pressure in African Americans
The evidence for the existence of genetic susceptibility variants for the common form of hypertension (“essential hypertension”) remains weak and inconsistent. As a result, a study published in PLOS Genetics (17 July 2009) conducting a genome-wide association study (GWAS) among African Americans, a population group in the United States that is disproportionately affected by hypertension and associated complications, including stroke and kidney diseases. Using a dense panel of over 800,000 SNPs in a discovery sample of 1,017 African Americans from the Washington, D.C., metropolitan region, the study identified multiple SNPs reaching genome-wide significance for systolic BP in or near the genes: PMS1, SLC24A4, YWHA7, IPO7, and CACANA1H. Two of these genes, SLC24A4 (a sodium/potassium/calcium exchanger) and CACNA1H (a voltage-dependent calcium channel), are potential candidate genes for BP regulation and the latter is a drug target for a class of calcium channel blockers. No variant reached genome wide significance for association with diastolic BP. The study replicated some of the significant SNPs in a sample of West Africans. Pathway analysis revealed that genes harboring top-scoring variants cluster in pathways and networks of biologic relevance to hypertension and BP regulation.
According to the authors, this is the first GWAS for hypertension and BP in an African American population and that the findings suggests that, in addition to or in lieu of relying solely on replicated variants of moderate-to-large effect reaching genome-wide significance, pathway and network approaches may be useful in identifying and prioritizing candidate genes/loci for further experiments.
Avastin Significantly Improves Survival for Patients with Recurrent and Metastatic Cervical Cancer
It is estimated that over 12,000 women will be diagnosed with cervical cancer in the United States in 2013 and over 4,000 women will die of the disease.
The mechanism of action of bevacizumab (Avastin) is to block the blood supply that feeds the tumor. The drug originally was approved for certain types of metastatic cancer in combination with chemotherapy and is designed to bind to and inhibit vascular endothelial growth factor (VEGF). VEGF is a protein that plays a critical role in tumor blood vessel growth.
According to an interim analysis of a large, randomized clinical trial, patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug. The clinical trial, known as GOG240, was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the Gynecological Oncology Group (GOG). Genentech, Inc., South San Francisco, Calif., the drug manufacturer, provided support for the trial under the Cooperative Research and Development Agreement (CRADA) with NCI.
The data safety monitoring committee overseeing the trial recommended that the results of a recent interim analysis be made public because the study had met its primary endpoint of demonstrating improved overall survival in patients who received bevacizumab, which also means that it delayed the chance of dying from the disease.
Patients who received bevacizumab got a dose of 15 milligrams per kilogram (mg/kg) of body weight with their chemotherapy treatment and continued with this dose one day every three weeks until disease progression or unacceptable toxicity occurred. Results showed that patients lived a median 3.7 months longer than those who did not receive bevacizumab. Patients treated with chemotherapy alone had a median survival of 13.3 months while those who received chemotherapy and bevacizumab had a median survival of 17 months. This survival difference was highly statistically significant. However, patients receiving bevacizumab experienced more side effects than those who did not. These side effects were consistent with side effects previously known to be associated with bevacizumab.
A total of 452 patients in the United States and Spain with metastatic, recurrent, or persistent cervical cancer not curable with standard treatment were enrolled between 2009 and 2012. The trial was designed to answer two questions: Whether topotecan in combination with paclitaxel was superior to cisplatin and paclitaxel in combination, and whether the addition of bevacizumab to either regimen improved overall survival.
Patients were randomly assigned to one of four treatment groups; two of the treatment groups received bevacizumab. In an analysis conducted in 2012, it was determined that topotecan plus paclitaxel was not superior to the standard therapy of cisplatin plus paclitaxel and investigators and patients were notified of the finding at that time.
Big Improvement In Diabetes Control Over Past Decades
About 26 million Americans have diabetes, and another 79 million have prediabetes, a condition that places them at increased risk for developing type 2 diabetes and heart disease. Between 1988 and 2012, the prevalence of diagnosed diabetes has more than doubled, from nearly 4% of the U.S. population to nearly 9%, according to data from the Centers for Disease Control and Prevention.
According to a report published online in Diabetes Care (15 February 2013), more people are meeting recommended goals in the three key markers of diabetes control. The study showed that from 1988 to 2010, the number of people with diabetes able to meet or exceed all three of the measures that demonstrate good diabetes management rose from about 2% to about 19%. Each measure also showed substantial improvement, with over half of people meeting each individual goal in 2010. However, despite improvement, the results show continued need for better diabetes control. In particular, young people and some minority groups were below average in meeting the goals.
The measures are A1C — which assesses blood sugar (glucose) over the previous three months — blood pressure and cholesterol. They are often called the ABCs of diabetes. When these measures fall outside healthy ranges, people are more likely to be burdened by complications of diabetes, including heart disease, stroke, kidney disease, blindness, and amputation.
To gauge diabetes management, researchers analyzed data from the National Health and Nutrition Examination Surveys from 1988-1994 and 1999-2010.
According to 2007-2010 data on Americans with diabetes:
— 53% met A1C goals, compared to 43% in 1988-1994 data
— 51% met blood pressure goals, compared to 33% in 1988-1994 data
— 56% met cholesterol goals, compared to 10% in 1988-1994 data
Improved cholesterol control was likely due to the increase in the use of statins, a type of cholesterol-lowering drug, from about 4% of people with diabetes during 1988-1994 to 51% during 2007-2010. Glucose control was worse in Mexican-Americans and in younger adults. Only 44% of Mexican-Americans met A1C goals, versus 53% of whites and blacks in 2007-2010 data. People between 20-49 years old were less likely to meet A1C goals than older people.
Goals for A1C, blood pressure, and cholesterol must be individualized for people with diabetes, as effects of diabetes can differ depending on a person’s age, type of diabetes, diabetes medications, complications from diabetes, and other factors.
For A1C, a goal for many people is below 7%. It is particularly important for people with long life expectancies to control A1C to protect against eye, nerve, and kidney disease in the future. Goals can be less stringent for people with limited life expectancy, since complications develop over time. For blood pressure, the goal for most people is 130/80. Moderate- or high-dose statin therapy is recommended for people over 40 with diabetes, with a goal of keeping the low-density lipoprotein (LDL) — sometimes called bad cholesterol — less than 100 milligrams per deciliter. Control of blood pressure and cholesterol are particularly important for lowering cardiovascular risk.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area
FDA Approves New Treatment for Late-Stage Breast Cancer
Breast cancer is the second leading cause of cancer-related death among women. An estimated 232,340 women will be diagnosed with breast cancer, and 39,620 will die from the disease in 2013, according to the National Cancer Institute.
HER2 is a protein involved in normal cell growth. It is found in increased amounts on some types of cancer cells (HER2-positive), including some breast cancers. In these HER2-positive breast cancers, the increased amount of the HER2 protein contributes to cancer cell growth and survival. Almost 20% of breast cancers have increased amounts of the HER2 protein.
This week, the FDA approved Kadcyla (ado-trastuzumab emtansine), a new therapy for patients with HER2-positive, late-stage (metastatic) breast cancer. Kadcyla is intended for patients who were previously treated with trastuzumab, another anti-HER2 therapy, and taxanes, a class of chemotherapy drugs commonly used for the treatment of breast cancer.
Referred to as T-DM1 during clinical research, Kadcyla was reviewed under the FDA’s priority review program, which provides for an expedited six-month review of drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products. Other FDA-approved drugs used to treat HER2-positive breast cancer include trastuzumab (1998), lapatinib (2007) and pertuzumab (2012).
The safety and effectiveness of Kadcyla were evaluated in a clinical study of 991 patients randomly assigned to receive Kadcyla or lapatinib plus capecitabine, another chemotherapy drug. Patients received treatment until either the cancer progressed or the side effects became intolerable. The study was designed to measure progression-free survival, the length of time patients lived without the cancer progressing, and overall survival, the length of time patients lived before death.
Results showed that patients treated with Kadcyla had a median progression-free survival of 9.6 months compared to 6.4 months in patients treated with lapatinib plus capecitabine. The median overall survival was 30.9 months in the Kadcyla group and 25.1 months in the lapatinib plus capecitabine group.
Kadcyla is being approved with a Boxed Warning alerting patients and health care professionals that the drug can cause liver toxicity, heart toxicity and death. The drug can also cause severe life-threatening birth defects, and pregnancy status should be verified prior to starting Kadcyla treatment. The most common side effects reported in patients treated with Kadcyla were nausea, fatigue, pain in the muscles or joints, low levels of platelets in the blood (thrombocytopenia), increased levels of liver enzymes, headache, and constipation.
Kadcyla, trastuzumab and pertuzumab are marketed by South San Francisco, Calif.-based Genentech, a member of the Roche Group. Lapatinib is marketed by GlaxoSmithKline, based in Research Triangle Park, N.C.
Mary Todd Lincoln’s Vanilla Almond Cake
There are reports attributable to President Lincoln that this cake of his wife’s was the best he ever ate. This delicious cake was the invention of Monsieur Giron, a Lexington, Kentucky caterer, who created it in honor of the visit to that city in 1825 of his fellow Frenchman, Lafayette. The Todd family acquired the recipe and cherished it ever after. The baking powder must have been added at a later date.
Vanilla (or almond extract)
Cream together 2 cups sugar with 1 cup butter. Sift 3 cups flour and 3 teaspoons baking powder three times and add to the butter-sugar mixture alternately with 1 cup milk. Chop 1 cup blanched almonds until very fine and add them to the mixture. Beat vigorously, then fold in 6 stiffly beaten egg whites carefully. Add 1 teaspoon vanilla, then fold in 6 stiffly beaten egg whites carefully. Add 1 teaspoon vanilla (almond extract if you prefer) and pour the mixture into a greased and floured angel-cake pan. Bake in a a preheated moderate (350 degree F.) oven for approximately 1 hour, or until a toothpick comes out clean when inserted into the cake’s center. Turn the cake out on a wire rack and allow to cool before frosting it. This makes a very large cake. If you prefer, you can bake it in 2 9-inch layer-cake pans. The cake may be made without the almonds and is a splendid plain white cake, very light and good.
This Vanilla-Almond cake could be made in one piece, as you see above, or as a layer cake, which would then need double the amount of frosting – for the top and between the two layers
“Family meals at the Lincolns’ were routine. Early in the morning the President liked a “good hot cup of coffee.” But often he would forget about breakfast until 9 or 10A.M. John Hay, one of Lincoln’s private secretaries, occasionally ate with the President. He noted that the frugal repast might consist of “an egg, a piece of toast, coffee, etc.” On occasion breakfast was a single egg. For lunch, Hay reported, Lincoln “took a little lunch–a biscuit, a glass of milk in winter, some fruit or grapes in summer…He ate less than anyone I know.” Lunch was usually eaten irregularly.” Source “A Treasury of White House Cooking,” Francois Rysavy [G. P. Putnam:New York] 1972 (p. 250)
Mary Todd Lincoln was born to a wealthy family in Lexington Kentucky. As such, she was well schooled in the fine aspects of social etiquette rather than the practical arts of domestic life. Her biographers note Mary’s early frugality and preference for simplicity. Her entertainments were well attended and, as one might expect, grew lavish in the White House period. She was especially fond of strawberries, and enjoyed giving strawberry sociables, where these fine fruits were combined with cake and ice cream.
“By the 1840s improved methods of salting and icing allowed Mary Lincoln to keep food longer than her mother could. Imported oysters, a delicacy on local menus, could be preserved for weeks by bountiful washing in salted water and some help from the weather. A few heretics (Mary Lincoln was not usually one of them) no longer baked bread, depending, instead, on a wagon that delivered bread, crackers, and cakes three times a week. The Springfield stores were beginning to sell prepared butter, and in season local farmers brought vegetables and fruits down Jackson Street for the unfixed prices that proper ladies were not supposed to contest. Penny-pinching Mary Lincoln was among those who violated the prescription that ladies don’t beat down prices, and she had several public battles with the fruit peddler over the prices of his less than perfect strawberries. Lincoln was never a fussy eater, and was satisfied most mornings with an apple for his breakfast. Still, he would be home for dinner in the middle of the day, and only delinquent housekeepers kept men waiting. But in Mary Lincoln’s home it was the husband whose casual sense of time and lack of appetite made regular hours an impossibility. Sometimes Abraham helped out by shopping…Even with improved technology and help with marketing, cooking took up the largest part of Mary Lincoln’s day.
Mary Lincoln learned to do what the kitchen slaves did: roast coffee, make calf’s-foot jelly, preserve fruit, and prepare cheese. In the summer the kitchen ran her, and it was both the repetitiveness and the lack of control that led disaffected matrons to compare themselves to slaves. Because she had not learned the vices of sugar and, like everyone in Springfield, innocently believed it the “most nourishing substance in nature,” she spent hours making puddings, cakes, candies, and cookies. By modern standards, the Lincoln household consumed a vast amount of sugar…Some of these sweets were eaten by others, for if Mary Lincoln was a novice cook, she was a practiced hostess with an easy charm that obscured any shortcomings in her menus. Her contemporary Julia Jayne Trumbull acknowledged her as the “prettiest talker in Springfield,”.”Mary Lincoln often entertained small numbers of friends at dinner and somewhat larger numbers at evening parties. Her table was famed for the excellence of its rare Kentucky dishes and in season was loaded with venison, wild turkeys, prairie chickens and quail and other game” – Mary Todd Lincoln: A Biography, Jean H. Baker [W.W. Norton:New York] 1987 (p. 109-113)
The Lincoln Family (ca. 1865). Francis Bicknell Carpenter, 1830-1900, oil on canvas. Image courtesy of the New York Historical Society.
Short History of Cake
The history of cake dates back to ancient times. The first cakes were very different from what we eat today. They were more bread-like and sweetened with honey. Nuts and dried fruits were often added. According to the food historians, the ancient Egyptians were the first culture to show evidence of advanced baking skills. The Oxford English Dictionary traces the English word cake back to the 13th century. It is a derivation of ‘kaka’, an Old Norse word. Medieval European bakers often made fruitcakes and gingerbread. These foods could last for many months.
According to the food historians, the precursors of modern cakes (round ones with icing) were first baked in Europe sometime in the mid-17th century. This is due to primarily to advances in technology (more reliable ovens, manufacture/availability of food molds) and ingredient availability (refined sugar). At that time cake hoops–round molds for shaping cakes that were placed on flat baking trays–were popular. They could be made of metal, wood or paper. Some were adjustable. Cake pans were sometimes used. The first icing were usually a boiled composition of the finest available sugar, egg whites and [sometimes] flavorings. This icing was poured on the cake. The cake was then returned to the oven for a while. When removed the icing cooled quickly to form a hard, glossy [ice-like] covering. Many cakes made at this time still contained dried fruits (raisins, currants, citrons).
It was not until the middle of the 19th century that cake as we know it today (made with extra refined white flour and baking powder instead of yeast) arrived on the scene. A brief history of baking powder. The Cassell’s New Universal Cookery Book [London, 1894] contains a recipe for layer cake, American. Butter-cream frostings (using butter, cream, confectioners [powdered] sugar and flavorings) began replacing traditional boiled icings in the first few decades of the 20th century. In France, Antonin Careme [1784-1833] is considered THE premier historic chef of the modern pastry/cake world. You will find references to him in French culinary history books.
Target Health in Israel on “Making it in NYC”
NYC is Going to Israel – Life Sciences Panel on Making it in NYC
The New York City Economic Development Corporation (NYCEDC) is the City’s primary engine for economic development charged with leveraging the City’s assets to drive growth, create jobs and improve quality of life. It is an organization dedicated to New York City and its people and uses its expertise to develop, advise, manage and invest to strengthen businesses and help neighborhoods thrive. NYCEDC also helps create affordable housing, new parks, shopping areas, community centers, cultural centers and much more.
The NYCEDC is coordinating a trip to Israel to discuss opportunities for Israeli companies and organizations to partner with NYC-based companies, organizations and Academic Medical Centers. In addition to a panel in Tel Aviv on Wednesday, April 10th, from 8:30-11am, there will be meetings at the Technion Institute of Technology in Haifa, the Hebrew University in Jerusalem and an Entreprenurial Event and CEO Roundtable in Herzilya.
As part of this exciting trip, Target Health Inc. is pleased to announce that Dr. Jules T. Mitchel was invited to participate in the panel entitled – Making it in NYC. On the panel will be representatives from NYC’s Life Sciences sector who will discuss case studies on academic-industry collaboration with NYC-based institutions, resources in clinical trials, funding, collaborative research opportunities and how to introduce Israeli technologies to the U.S. market.
The Making it in NYC panel will be moderated by Aaron Etra, Secretary-Treasurer, Institute for Life Sciences Collaboration and will feature:
Yuval Cohen, CEO, Morria Biopharmaceuticals
Jules Mitchel, President, Target Health Inc.
Bryan Spielman, EVP Strategy and Corporate Development, Medidata Solutions
Abram Goldfinger, Executive Director Technology Transfer, NYU School of Medicine.
RSVPs and inquiries can be sent to firstname.lastname@example.org with the subject line Life Sciences Panel.
For more information about Target Health contact Warren Pearlson ( 212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website
Lilly and QIAGEN and Companion Diagnostics
Companion diagnostics unlock a patient’s molecular information in order to guide treatment decisions for specific cancers or other diseases.
On February 13th it was announced that Eli Lilly and QIAGEN entered into a master collaboration agreement for the development and commercialization of companion 1) ___ for pairing with Lilly investigational and approved medicines across all therapeutic areas. The agreement provides a framework for Lilly and QIAGEN to collaborate on future projects across all of Lilly’s therapeutic areas with the goal of bringing to market Lilly 2) ___ paired with QIAGEN diagnostics. It also further underscores QIAGEN’s leading position in partnering with global pharmaceutical companies to deliver the benefits of personalized medicine to patients and healthcare providers.
Tailored therapies are a key component of Lilly’s strategy of providing improved outcomes for individual 3) ___. By working with partners like QIAGEN, we are advancing a number of tailored therapeutics in an effort to target the right medicine to the right patient, said Daniel Skovronsky, M.D., Ph.D., vice president, tailored therapeutics, Lilly, and chief executive officer, Avid Radiopharmaceuticals, which is a wholly-owned subsidiary of Lilly. This agreement lays the groundwork for potential future projects with Lilly in various therapeutic areas and enables significant efficiencies for future development programs by 4) ___ interfaces and processes between the organizations. Through partnerships like this, QIAGEN offers pharma companies a cost-effective way to maximize the value and benefits of potential new medicines in their pipelines, while also reducing the risks in medicine development.
QIAGEN is at the forefront globally in developing and validating Personalized Healthcare tests that provide physicians with 5) ___ information on each patient to guide the selection of medicines in treating cancer and other diseases. QIAGEN is actively expanding its pipeline of tests for important biomarkers and intends to submit several companion diagnostics for U.S. regulatory approval. Last month, QIAGEN announced submission of its therascreen® EGFR RGQ PCR Kit test to the FDA as a proposed companion diagnostic to guide treatment with a new investigational oncology compound developed by Boehringer Ingelheim.
QIAGEN and Lilly have previously collaborated on companion diagnostics designed to run on QIAGEN’s Rotor-Gene Q system, a component of the QIA symphony family of automated instruments, which is revolutionizing 6) ___ workflows. QIAGEN’s strategy is to develop FDA-approved diagnostics in the United States for use on this platform.
QIAGEN N.V., a Netherlands holding company, is the leading global provider of Sample & Assay Technologies that are used to transform biological materials into valuable molecular information. Sample technologies are used to isolate and process DNA, RNA and proteins from 7) ___ samples such as blood or tissue. Assay technologies are then used to make these isolated biomolecules visible and ready for interpretation.
Last year, Qiagen’s KRAS RGQ PCR helped Lilly and partner Bristol-Myers Squibb nail down an expanded indication for 8) ___ drug Erbitux. Now, Lilly is employing the company to collaborate on treatments across all its therapeutic areas, a deep dive into companion diagnostics and personalized medicine for the drugmaker. The big Erbitux approval seems to have galvanized Lilly’s commitment to companion diagnostics, as the Qiagen deal follows a similar one last month when Lilly signed on with Agilent’s Dako diagnostics unit to develop assays for its oncology pipeline. Before that, the Lilly partnered with 2012 Fierce 15 winner PrimeraDx to use that company’s ICEPlex assay-development platform.
Big Pharma’s big buy-in to companion diagnostics is unlikely to shrink, as more and more blockbuster hopefuls are being developed with matching assays designed to sway regulators, payers and patients. Roche leads the pack, with CEO Severin Schwan saying 60% of the company’s pipeline treatments will be packaged with complementary 9) ___. And fellow heavyweights Pfizer, AstraZeneca and BMS have all reached out to diagnostics companies to help target their treatments.
Qiagen’s KRAS RGQ PCR Kit
The FDA approved the KRAS RGQ PCR Kit the same day it approved an expanded indication for Erbitux and analysts hailed the pairing as a victory for 10) ___ medicine. Erbitux was already approved for head and neck cancer, but with Qiagen’s assay identifying the colorectal cancer patients who would respond to the therapy, BMS and Lilly were able to persuade the FDA. The test IDs patients with so-called wild-type KRAS genes, about 60% of whom benefit from Erbitux, according to Qiagen. Weeding out patients who won’t respond to the drug could save about $600 million a year in the U.S., the company says, and that’s music to the ears of payers.
While the Erbitux-KRAS test combo stood out in 2012, many in the life sciences world say the blockbusters of the future will come hand-in-hand with companion diagnostics. Twenty years ago, the paradigm was that for every 100 cancer patients treated, 10 benefited, UBS analyst Gbola Amusa told the Financial Times. If you could instead only treat those 10 patients, you get the same result without putting through 90 who don’t benefit, and society gains. Ten years from now, this will be standard.
ANSWERS: 1) diagnostics; 2) medicines; 3) patients; 4) standardizing; 5) genomic; 6) laboratory; 7) biological; 8) cancer; 9) tests; 10) personalized