New Publication in the Journal Monitor (ACRP)

 

Target Health is pleased to announce a new publication entitled “A 21st Century Approach to QA Oversight of Clinical Trial Performance and Clinical Data Integrity (http://www.targethealth.com/PDF/Articles/13498-10_Mitchel.pdf) published in the December edition of Monitor (publication of ACRP). The following is a brief summary:

 

“Monitoring is considered a quality control (QC) process (ongoing activities to assure quality), whereas audits are considered quality assurance (QA). QA procedures are not typically an integral part of a drug development program, but encompass a process that occurs during or after “the fact.“ Thus, it is not uncommon for corrective actions to occur too late to allow for meaningful changes, and for trial managers to spend an inordinate amount of time writing “notes to file“ and performing “crisis management.“ In order to address this issue, a drug development program was initiated using a quality-by-design (QbD) approach, recognizing that (a) change will be difficult to implement and (b) often quality departments are “feared“ and have powerful roles in companies. Paying heed to such concerns, an independent quality expert was assigned to the development team with the mandate to assure proactive and upfront quality planning at all stages of development.“

 

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

The Original Rorschach Test (1921) – Test Yourself, Take the Test

 

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A Song Dynasty (960 to 1279) painting of candidates participating in

the imperial examination, a rudimentary form of psychological testing,

first done in China

 

Shortly after publication of Dr. Hermann Rorschach’s book, a copy found its way to Japan where it was discovered by one of the country’s leading psychiatrists in a second-hand book store. He was so impressed that he started a craze for the test that has never diminished. The Japanese Rorschach Society is by far the largest in the world and the test is “routinely put to a wide range of purposes”. The test has recently been described as “more popular than ever” in Japan.

 

Take Hermann Rorschach’s Original Rorschach Test (1921)

 

Directions:

 

Look at images 1 through 10 and quickly (without thinking) write down the first word that comes to your mind, evoked by each image. There are no right or wrong answers here. At the bottom of the page, we will simply list the most common mental-picture responses, given for each of the 10 Rorschach inkblots.

 

Image 1

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Image 2

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Image 3

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Image 4

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Image 5

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Image 6

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Image 7

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Image 8

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Image 9

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Image 10

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Most common responses to Rorschach inkblot images, 1 through 10

 

Image 1: Bat, butterfly, moth

Image 2: Two humans, two elephants, dogs, bears

Image 3: Two humans

Image 4: Animal hide, skin, rug

Image 5: Bat, butterfly, moth

Image 6: Animal hide, skin, rug

Image 7: Human heads or faces

Image 8: Animal; not cat or dog

Image 9: Humans (orange section)

Image 10: Crab, lobster, spider

Hermann Rorschach MD (1884-1922)

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Rorschach in about 1910

 

Hermann Rorschach MD, was a Swiss Freudian psychiatrist and psychoanalyst, best known for developing a projective test known as the Rorschach inkblot test. This test was reportedly designed to reflect unconscious parts of the personality that “project“ onto the stimuli. In the test, individuals are shown 10 inkblots – one at a time – and asked to report what objects or figures they see in each of them. Using interpretation of “ambiguous designs“ to assess an individual’s personality is an idea that goes back to Leonardo da Vinci and Botticelli. Interpretation of inkblots was central to a game, Gobolinks, from the late 19th century. Rorschach’s, however, was the first systematic approach of this kind.

 

Rorschach was born in Zurich and spent his childhood and youth in Schaffhausen, in northern Switzerland. His mother died when he was twelve. He was known to his school friends as Klecks, or “inkblot“ since he enjoyed klecksography, the making of fanciful inkblot “pictures“. Rorschach’s father, an art teacher, encouraged him to express himself creatively through painting and drawing conventional pictures. As the time of his high school graduation approached, he could not decide between a career in art and one in science. He wrote a letter to the famous German biologist Ernst Haeckel asking his advice. The scientist suggested science, and Rorschach enrolled in medical school at the University of Zurich. Rorschach studied under the eminent psychiatrist Eugen Bleuler, who had taught Carl Jung. Even before the young Rorschach began to study psychology, the medical profession had flirted with imagery association. In 1857, a German doctor named Justinus Kerner published a book of poetry, with each poem inspired by an accompanying inkblot. Alfred Binet, the father of intelligence testing, also tinkered with inkblots at the outset of the 21st century, seeing them as a potential measure of creativity. While stating that Rorschach was familiar with these particular ink blotches reaches no further than educated conjecture, we know that he was familiar with the work of Szyman Hens, an early psychologist who explored his patients’ fantasies using inkblots, as well as Carl Jung’s (learned from Freud) practice of having his patients engage in word-association and (Freud’s words), “the royal road to the unconscious“ which is dream analysis.

 

The excitement in intellectual circles over psychoanalysis constantly reminded Rorschach of his childhood inkblots. Wondering why different people often saw entirely different things in the same inkblots, he began, while still a medical student, showing inkblots to schoolchildren and analyzing their responses. In 1857 German doctor Justinus Kerner had published a popular book of poems, each of which was inspired by an accidental inkblot, and it has been speculated that the book was known to Rorschach. French psychologist Alfred Binet had also experimented with inkblots as a creativity test and, after the turn of the century, psychological experiments where inkblots were utilized multiplied, with aims such as studying imagination and consciousness.

 

By July 1914 Rorschach had returned to Switzerland, where he served as an Assistant Director at the regional psychiatric hospital at Herisau, and in 1921 he wrote his book Psychodiagnostik, which was to form the basis of the inkblot test. The Inkblots were an overnight success due to the seemingly miraculous behavior readings they provided. However, they have been considered pseudoscience and remain controversial.

 

After noticing that schizophrenic patients associated vastly different things with inkblots than other patients, Rorschach, following some experimentation, created the first version of the inkblot test as a measure of schizophrenia in 1921. The test, however, only came to be used as a form of personality assessment when Samuel Beck and Bruno Klopfer expanded its original scope in the late 1930s. Since then, psychologists have frequently used the various aspects of people’s responses (e.g., inkblot focus area) to make judgment calls about broad personality traits. Ironically, Rorschach himself had been skeptical about the inkblots’ value in assessing personality.

 

After studying 300 mental patients and 100 control subjects, in 1921 Rorschach wrote his book Psychodiagnostik, which was to form the basis of the inkblot test (after experimenting with several hundred inkblots, he selected a set of ten for their diagnostic value). Although he had served as Vice President of the Swiss Psychoanalytic Society, Rorschach had difficulty in publishing the book and it attracted little attention when it first appeared.

 

Only one year after writing his book, however, Rorschach died of peritonitis at the age of 37, on 1 April 1922, probably resulting from a ruptured appendix.

 

In 1927, the newly founded Hans Huber publishing house purchased Rorschach’s book Psychodiagnostik from the inventory of Ernst Bircher. Huber has remained the publisher of the test and related book, with Rorschach a registered trademark of Swiss publisher Verlag Hans Huber, Hogrefe AG. The work has been described as “a densely written piece couched in dry, scientific terminology“.

 

After Rorschach’s death, the original test scoring system was improved by Samuel Beck, Bruno Klopfer and others. John E. Exner summarized some of these later developments in the comprehensive system, at the same time trying to make the scoring more statistically rigorous. Some systems are based on the psychoanalytic concept of object relations. The Exner system remains very popular in the United States, while in Europe other methods sometimes dominate, such as that described in the textbook by Evald Bohm, which is closer to the original Rorschach system and rooted more deeply in the original psychoanalysis principles.

 

Rorschach never intended the inkblots to be used as a general personality test, but developed them as a tool for the diagnosis of schizophrenia. It was not until 1939 that the test was used as a projective test of personality, a use of which Rorschach had always been skeptical. Interviewed in 2012 for a BBC Radio 4 documentary, Rita Signer, curator of the Rorschach Archives in Bern, Switzerland, suggested that far from being random or chance designs, each of the blots selected by Rorschach for his test had been meticulously designed to be as ambiguous and “conflicted“ as possible.

 

There is a well-known scene in Woody Allen’s Take The Money And Run (1969) when Virgil Starkwell (Allen) takes a psychological test to join the Navy, but is thwarted by his lascivious unconscious. The psychological measure that proves to be Starkwell’s undoing – rejected, he turns to a life of crime – is the Rorschach inkblot test. Although Rorschach died very young, his namesake remains embedded in our perception of psychology, alongside Freud’s couch and Pavlov’s dog.

ONCOLOGY

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Low-Intensity Therapy for Burkitt Lymphoma is Highly Effective

 

Lymphoma is a cancer that begins in cells of the immune system. Burkitt lymphoma, is a disease that occurs frequently in immune-suppressed AIDS patients, and is the most aggressive type of lymphoma. It is more common in equatorial Africa than in Western countries. In Uganda, for example, the estimated prevalence of Burkitt lymphoma is between 5 and 20 cases per 100,000 inhabitants, whereas in the US, according to the National Cancer Institute’s (NCI’s) statistical database for 2001-2009, prevalence was 0.4 cases per 100,000 inhabitants. Cure rates for Burkitt lymphoma in Western countries approach 90% in children, which is higher than adult cure rates seen prior to this new approach to treatment, whereas only 30% to 50% of children in Africa are cured due to an inability to safely administer high-dose treatment. Thus, there is an important need for less toxic and more effective therapies.

 

Standard treatment for Burkitt lymphoma involves high-dose chemotherapy, which has a high rate of toxicity, including death, and cures only 60% of adult patients. According findings in a new clinical trial, published online in the New England Journal of Medicine (14 November 2013), adult patients with Burkitt lymphoma had excellent long-term survival rates — upwards of 90% — following treatment with low-intensity chemotherapy regimens.

 

The trial involved two variants of EPOCH-R, a chemotherapy regimen that includes the drugs etoposide (E), prednisone (P), vincristine (Oncovin), cyclophosphamide (C), doxorubicin (Hydrodoxorubicin), and rituximab (R). EPOCH-R involves longer exposures to lower concentrations of drugs instead of briefer exposures to higher concentrations of drugs. Previously, it was found that EPOCH-R was very effective for treating mediastinal B-cell lymphoma, a disease that is distinct from Burkitt lymphoma.

 

Thirty patients with previously untreated Burkitt lymphoma were included in the trial. The patients received one of the two EPOCH-R variants, depending on their HIV status. Nineteen HIV-negative patients received dose-adjusted (DA)-EPOCH-R, whereas 11 HIV-positive patients received SC-EPOCH-RR, which is a short-course (SC) variant of EPOCH-R that includes two doses of rituximab per treatment cycle and has a lower treatment intensity than DA-EPOCH-R. Adjustment of dose levels was done to try to provide the optimum amount of drug based on a person’s tolerance of chemotherapy. The median age of the patients was 33 years old and most had intermediate- or high-risk disease. No treatment-related deaths occurred and the principal toxicities seen in the trial were fever and neutropenia (low white blood cell counts). With median follow-up times of 86 and 73 months, the overall survival rates were 100% and 90%, respectively, with DA-EPOCH-R and SC-EPOCH-RR.

 

According to the authors, the toxicity of EPOCH-R-based treatment in Burkitt lymphoma is considerably less than that reported with standard Burkitt regimens and that the promising study results with low-toxicity treatment suggest that this approach may be effective and worth investigating in certain geographic and economically challenged regions where Burkitt lymphoma is highly prevalent.

 

Based on these results, two trials to confirm the efficacy of EPOCH-R therapy in adult and pediatric Burkitt lymphoma patients are under way.

Earliest Marker for Autism Found in Young Infants

 

Typically, developing children begin to focus on human faces within the first few hours of life, and they learn to pick up social cues by paying special attention to other people’s eyes. Children with autism, however, do not exhibit this sort of interest in eye-looking. In fact, a lack of eye contact is one of the diagnostic features of the disorder. Autism isn’t usually diagnosed until after age 2, when delays in a child’s social behavior and language skills become apparent. Therefore, the sooner it is possible to identify early markers for autism, the more effective treatment interventions can be.

 

According to an article published online in Nature (6 November 2013), eye contact during early infancy may be a key to early identification of autism. The study reveals the earliest sign of developing autism ever observed is a steady decline in attention to others’ eyes within the first two to six months of life.

 

To find out how this deficit in eye-looking emerges in children with autism, the authors followed infants from birth to age 3. The infants were divided into two groups, based on their risk for developing an autism spectrum disorder. Those in the high risk group had an older sibling already diagnosed with autism; those in the low risk group did not. Eye-tracking equipment was used to measure each child’s eye movements as they watched video scenes of a caregiver. The authors calculated the percentage of time each child fixated on the caregiver’s eyes, mouth, and body, as well as the non-human spaces in the images. Children were tested at 10 different times between 2 and 24 months of age.

 

Results showed that by age 3, some of the children — nearly all from the high risk group — had received a clinical diagnosis of an autism spectrum disorder. The authors then reviewed the eye-tracking data to determine what factors differed between those children who received an autism diagnosis and those who did not. In infants later diagnosed with autism, there was a steady decline in how much they look at their mother’s eyes. This drop in eye-looking began between two and six months and continued throughout the course of the study. By 24 months, the children later diagnosed with autism focused on the caregiver’s eyes only about half as long as did their typically developing counterparts.

 

This decline in attention to others’ eyes was somewhat surprising. In opposition to a long — standing theory in the field-that social behaviors are entirely absent in children with autism — these results suggest that social engagement skills are intact shortly after birth in children with autism. According to the authors, if clinicians can identify this sort of marker for autism in a young infant, interventions may be better able to keep the child’s social development on track.

 

The following graphic from the NIH contains an example stimuli overlaid with eye-tracking data. Click on the link below.

 

Decline in eye fixation reveals signs of autism present already within the first 6 months of life. Data from a 6-month-old infant later diagnosed with autism are plotted in red. Data from a typically developing 6-month-old are plotted in blue. The data show where the infants were looking while watching a video of a caregiver.Source: Warren Jones, Ph.D., Marcus Autism Center, Children’s Healthcare of Atlanta, and Emory University School of Medicine

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.

 

FDA Approves Imbruvica for Rare Blood Cancer – Second Drug with Breakthrough Therapy Designation to Receive FDA Approval

 

Mantle cell lymphoma (MCL) is a rare form of non-Hodgkin lymphoma and represents about 6% of all non-Hodgkin lymphoma cases in the US. By the time MCL is diagnosed, it usually has already spread to the lymph nodes, bone marrow and other organs.

 

The FDA has approved Imbruvica (ibrutinib) to treat patients with mantle cell lymphoma (MCL). Imbruvica is intended for patients with MCL who have received at least one prior therapy. It works by inhibiting the enzyme needed by the cancer to multiply and spread. Imbruvica is the third drug approved to treat MCL. Velcade (2006) and Revlimid (2013) are also approved to treat the disease.

 

Imbruvica is the second drug with breakthrough therapy designation to receive FDA approval. The Food and Drug Administration Safety and Innovation Act, passed in July 2012, gave the FDA the ability to designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.

 

The FDA has approved Imbruvica under the agency’s accelerated approval program, which allows the FDA to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. The FDA also granted Imbruvica priority review and orphan-product designation because the drug demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition and is intended to treat a rare disease, respectively.

 

Imbruvica’s accelerated approval for MCL is based on a study where 111 participants were given Imbruvica daily until their disease progressed or side effects became intolerable. Results showed nearly 66% of participants had their cancer shrink or disappear after treatment (overall response rate). An improvement in survival or disease-related symptoms has not been established.

 

The most common side effects reported in participants receiving Imbruvica are low levels of platelets in the blood (thrombocytopenia), diarrhea, a decrease in infection-fighting white blood cells (neutropenia), anemia, fatigue, musculoskeletal pain, swelling (edema), upper respiratory infection, nausea, bruising, shortness of breath (dyspnea), constipation, rash, abdominal pain, vomiting, and decreased appetite. Other clinically significant side effects include bleeding, infections, kidney problems and the development of other types of cancers.

 

Imbruvica is co-marketed by Sunnyvale, Calif.-based Pharmacyclics and Raritan, N.J.-based Janssen Biotech, Inc. Velcade (bortezomib) is marketed by Millennium Pharmaceuticals, based in Cambridge, Mass. Revlimid (lenalidomide) is marketed by Summit, N.J.-based Celgene.

Parsnips with Sweet Potato, Squash, Agave, Walnuts and Seeds

 

First of all, we’re happy to announce that Vanessa Hays, is contributing to the ON TARGET newsletter and for starters, will add to the Target Healthy Eating column, an analysis of the recipes including a calorie counter and a nutrition guide (see below), as well as additional recipes, etc.; more as time goes on.

 

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Is it normal to get so worked up over a recipe? Maybe, I’d better take that Rorschach Test that I gave everyone else to take, LOL. Seriously, this recipe is a labor of love, sensitive taste buds and a dash of creativity, if I do say so myself. And, just in time for Thanksgiving, if you still have room on your menu. You won’t be sorry if you squeeze it in and I promise, your family and any guests will love it.

 

Ingredients

 

1 pound of parsnips

1 and 1/4 pounds sweet potatoes

1 carrot

1 fresh butternut squash or 1 box frozen butternut squash

2 Tablespoons Canola oil, plus extra for brushing

1 packed Tablespoon of freshly grated horseradish, or bottled

Pinch salt (optional)

Pinch black pepper (grind to your taste)

4 Tablespoons, Sugar-free maple syrup or agave

1 teaspoon, Chopped walnuts

1 teaspoon, sunflower seeds

1 teaspoon pumpkin seeds, pepitas

1/3 cup tofutti (soy cream cheese)

 

 

 

Nutrition Facts

Serving Size 201 grams  or 7 oz

 

 

Amount Per Serving % Daily Value
   
Calories

221

Calories from Fat

71

  % Daily Value
Total Fat

7.8g

12%
Saturated Fat

1.4g

7%
Trans Fat

0.0g

 
Cholesterol

0mg

0%
Sodium

110mg

5%
Total Carbohydrates

35.5g

12%
Dietary Fiber

7.2g

29%
Sugars

10.4g

 
Protein

3.6g

 

 

 

Vitamin A 397%

Vitamin C 54%

Calcium 7%

Iron 7%

 

Nutrition Grade A

 

* Based on a 2000 calorie diet

 

 

According to this analysis, one serving of this recipe is approximately one cup.

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Just before adding the nut/seed topping

 

 

Directions

 

 

1. Preheat oven to 350 degrees

 

2. Scrub well, then peel all the root veggies. Cut into thick pieces. Brush the pieces with oil and place on slightly oiled cookie sheet. Sprinkle with salt (optional) and black pepper to your taste.

 

3. Roast the root veggies in the oven until soft, 40 to 50 minutes.

 

4. Remove from oven and place in large bowl. (don’t turn off the oven) With a hand masher, mash the veggies until they reach your desired texture. You don’t want a puree here; you want a certain amount of texture left, with bits of the veggies visible.

 

5. To the mashed veggies, add 1 Tablespoon of the sugar-free syrup or agave, add the tofutti, horseradish, salt (optional), more black pepper (optional). Stir all of these ingredients until well distributed and with a large server, spoon this mixture into the baking dish you plan to serve from.

 

6. In a small bowl, add the sugar-free maple syrup or agave, and the walnuts and seeds. Stir this well, and allow the seed mixture to ooze all over the top of your root casserole.

 

7. Place back in oven for about 10 minutes until the topping is slightly absorbed and the seeds get a little toasty. Check this after 5 minutes to be sure the seeds don’t burn. They’re great toasted, but not burnt.

 

This Veggie Root Mash, is good with turkey, chicken, quail, squab or any fish or seafood.

 

We’re in a Sauvignon Blanc mood lately, so we’ll stick with that, to go with all of the above.

 

As I said last week, we don’t crave traditional Thanksgiving desserts, so won’t have any of those pies. However, I have just gotten a sudden impulse to experiment with beautiful orange persimmons that are in season now. Although, my thinking could change, I’m in a mood to try to create persimmon mousse. If it works out, I’ll share it in the next newsletter. Until then, have a wonderful Thanksgiving, wherever you are.

 

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“Freedom From Want“ by Norman Rockwell, 1943

 

Freedom from Want or The Thanksgiving Picture is one of Four Freedoms paintings by Norman Rockwell that were inspired by United States President Franklin D. Roosevelt in the State of the Union Address, known as Four Freedoms, he delivered to the 77th United States Congress on January 6, 1941. The other paintings in this series were Freedom of Speech, Freedom from Fear, and Freedom of Worship.

 

Of the four paintings, this is the one most often seen in art books with critical review and commentary. The painting has become a nostalgic symbol of an enduring American theme of holiday celebration. Although all four images were intended to promote patriotism in a time of war, Freedom from Want, which depicts an elderly couple serving a fat turkey to what looks like a table of happy and eager children and grandchildren, has given the idealized Norman Rockwell Thanksgiving work an important place in the enduring marketplace of promoting family togetherness, peace and plenty.

 

Outside of the United States, this image is perceived as a depiction of American overabundance. This painting depicts the common positive Rockwell themes of American prosperity and dependability for a generation who looked to Rockwell to appeal to their traditional values. This image of family life is an example of the regionalism and idealism that dominate Rockwell’s work. Rockwell summed up his own form of idealism best: “I paint life as I would like it to be.“

 

The abundance and unity shown, were the idyllic hope of a world still ravaged by the most terrible violence the planet had ever experienced, WW2.