Cooperative Research Ethics Review Boards: A Win-Win Solution?

Enhancing public participation in research is one of the central challenges facing the clinical research enterprise in the United States, and one of its highest priorities.^[1] Public concern about the safety of participating in research is increasing, reflected in a rising tide of litigation, negative articles in the popular press, and other published commentaries.^[2] Part of this concern focuses on Research Ethics Review Boards (Research ERBs)the entities responsible for ethical review and oversight of human research. These bodies, referred to in federal regulations as Institutional Review Boards (IRBs), are overburdened and often characterized as inefficient and ineffective.^[3] The increasing number of multi-center studies is exacerbating current problems, as they often require duplicative reviews.^[4] Multiple submissions of a single protocol and its associated consent documents to several Research ERBs for review and alterations create redundancy without necessarily enhancing the protection of research subjects.^[5]

Many parties, including the Institute of Medicine (IOM), the National Bioethics Advisory Commission (NBAC), and the Department of Health and Human Services (DHHS), note that these duplicative reviews can actually detract from subject protections by diverting time and resources from more effective uses; they have suggested streamlining review through the use of alternative models.^[6] Collaborative approaches to ethical review that capture the best of both central and local processes could be more efficient, less costly and less demanding of limited resources, and also be more effective. They may allow for more timely data collection and analysis of adverse events, address the problem of institutional conflict of interest, and offer more options for unaffiliated investigators and patients with rare diseases.^[7]

Central review boards have taken on increasing importance in recent years. Reference to a "central IRB" does not necessarily mean that one Research ERB is always the IRB of record; use of the term "cooperative review" may more accurately reflect the emerging approaches discussed in this article. In a survey by the Association of American Medical Colleges (AAMC) of research deans at institutions using a Central IRB (defined as any noninstitutional board or cooperative arrangement), 53% agreed that its use shortened time to approval of research protocols. Eighty-four percent were pleased with the Central IRB review, and 77% indicated that they were able to maintain excellent local oversight of studies approved by a Central IRB.^[8] Notably, some highly respected academic institutions have turned to well-established commercial review boards after deficiencies in their local boards and processes resulted in significant enforcement actions by federal regulatory agencies. One of these private boards was among the first human research protection programs (HRPP) to receive full accreditation by the Association for Accreditation of Human Research Protection Programs (AAHRPP); the Partnership for Human Research Protection (PHRP) also has accredited independent review boards.

Many institutions are hesitant to use cooperative review mechanisms for a variety of reasons. According to the AAMC survey, those who have not used Central IRBs (76% of respondents) did not do so because of concerns about liability (73%), additional costs (60%), the absence of local representation (86%), and the inability to assess the quality of the services (56%). Federal regulations require that research review boards have "sensitivity to such issues as community attitudes,"^[9]and many institutions feel that local review is an essential component of ethical research; to what extent this view also reflects a desire to maintain institutional autonomy is unknown. Both the Office for Human Research Protections (OHRP) and the Food and Drug Administration (FDA) have responded to the increasing number of multi-center trials by clarifying that existing regulations permit institutions to use joint review, rely on another qualified IRB, or make similar arrangements to avoid duplication of effort for cooperative research.^[10] OHRP and FDA also have issued further guidance that clarifies the implementation of such arrangements to ensure that the local context is taken into account.^[11]

Already, some academic organizations and the National Cancer Institute (NCI) are utilizing cooperative models to streamline the Research ERB review process. To explore the potential of these emerging ethical review mechanisms, the Clinical Research Roundtable of the IOM recently convened stakeholders in the clinical research enterprise to hear from those involved in these efforts.^[12] In this paper, we describe several models of cooperative review, many of which were presented at the meeting. These models include the Multicenter Academic Clinical Research Organization (MACRO), the Biomedical Research Alliance of New York (BRANY), independent Research ERBs, the NCI's Central IRB, and Regional Ethics Organizations (REOs). Many of these models are in the formative stages, and REOs, which are now utilized in the United Kingdom, do not exist in the U.S. at this time.^[13] Therefore, key evaluative data regarding existing central review mechanisms are not presently available; indeed, more data are needed to assess both traditional and cooperative review mechanisms and to more fully and scientifically compare these options. Our assessment is based upon the best available data about these efforts. Key issues about centralized review relate to perceived legal liability by cooperating academic institutions regarding the ability to fully reflect and address local concerns.

1. Describe all factors that result in rigor mortis that occurs after the death of an individual.

2. Please provide short answers to the following questions:

1. How is a skeletal muscle fiber categorized as either fast or slow?

2. Which skeletal muscle fibers have many capillaries and many mitochondria? Why?

3. What color are oxidative fibers? Justify why.

3. Suzane was riding her bicycle on a busy street when a car made a sudden right turn out of the left lane of traffic directly in front of her. Though she hit her brakes as hard as she could, she ended up crashing into the rear door of the vehicle at a high speed. Immediately after hitting the ground she felt a sudden, sharp pain in the left side of her thorax and experienced sudden dyspnea (shortness of breath, difficulty breathing). Given her symptoms, what has likely happened to Suzane? Explain as completely as possible the mechanisms behind her injury and symptoms.

4. Coal miners who spend years inhaling fine coal dust have much of their alveolar surface covered with scar-like tissue. How would this condition affect exchange of gases between alveoli and capillaries? Explain in details.

5. A track sprinter has just completed a 200-m sprint. His legs are “burning” as lactic acid builds up within his muscle cells. This lactic acid is produced as his muscle cells increase the rate of glycolysis and fermentation to provide the necessary ATP to power the quick muscular contractions necessary during sprinting. The production of excess lactic acid in skeletal muscle cells leads to local acidosis (i.e. decreased pH) of the tissues.

1. What effect does local acidosis have on the delivery of oxygen to the working tissues?
2. What is this effect called?
3. Why is it important in this situation?

Symptom Presentation: Cortisol: Increased production of cortisol by the adrenal cortex Bone Loss: Decreased bone mineral density (BMD) confirmed via dual-energy x-ray absorptiometry (DEXA) Previously, you researched and considered three conditions through the process of differential diagnosis that would present with varying abnormalities in homeostasis, metabolism, triglycerides and DNA in week 1 and abnormalities in oxidation, plasma and tissue enzyme activity, inflammation and alopecia respectively in week 2. Given the new symptom presentation above, consider and answer the following questions within a video or written presentation: If choosing a video presentation, spend a minimum of one minute on each of the three questions below. If choosing a written presentation, create a 2-3 paragraphs per each of the questions listed below. Given the new presenting symptoms listed above, has your diagnosis from week 2 changed? Why or why not? Is there a correlation between increased cortisol production and bone loss or are these two separate unassociated symptoms? Rationalize your choice. Does the current symptom presentation from weeks 1, 2 and 3 align with endocrine (hormonal) imbalances? Rationalize your answer. Within your video or written presentation, please be certain to validate your opinions and ideas while disclosing the sources utilized within your video presentation or written presentation (APA format).

Internal respiration refers to the exchange of gases between the blood in ____________ capillaries and the tissue fluid. Internal respiration services tissue cells, and without internal respiration, cells could not continue to produce the ____________ that they need as an energy source. Blood in the systemic capillaries is a ____________ color because of the presence of oxyhemoglobin. Oxyhemoglobin gives up ____________ , which diffuses out of the blood into the tissues. Oxygen diffuses out of the blood into the tissues because the ____________ of tissue fluid is lower than that of blood. This is because cells continuously use up ____________ in cellular respiration.

ATP Pc?? blue bright red carbon dioxide glucose organ oxygen pulmonary systemic P??

The respiratory system functions in both external and internal respiration. ____________ respiration refers to the exchange of gases between air in the alveoli and blood in the ____________ capillaries. Gases exert pressure, and the amount of pressure each gas exerts is called its ____________ pressure. Compared to atmospheric air, blood in the capillaries has a ____________ partial pressure, therefore, CO? diffuses out of the blood into the lungs. Most of the CO2 in the blood exists as bicarbonate ions. As free CO2 is exhaled by the lungs, more hydrogen ions combine with bicarbonate to form ____________ . The enzyme ____________ , present in red blood cells, speeds the breakdown of this substance into more CO2 and H2O.

External Internal atmospheric carbon monoxide carbonic acid carbonic anhydrase erythrocytic amylase higher lower partial pulmonary thoracic

Which factor is more than likely the reason for the rapid speed of action of injected drugs?

Question 16 options:

1)

How quickly the substance enters the bloodstream

2)

How quickly it reaches the site of action

3)

How much of the drug reaches the target site

4)

All of the above

Question 17 (1 point)
A new drug is being developed to treat acne. Scientists have found that a therapeutic does is about 150mg, and that an increase of 5mg is sufficient to cause bizarre skin rashes. This new drug has narrow:

Question 17 options:

1)

Site of action

2)

Potency to toxicity ratio

3)

Margin of safety

4)

Dose-response curve

Question 18 (1 point)
When a person is given a dose of 2mg of Ativan, it takes approximately 6 hours for 1mg of Ativan to leave the body. This refers to Ativan's

Question 18 options:

1)

Time to biotransformation

2)

Plateau effect

3)

Rate of metabolism

4)

Half life

Question 19 (1 point)
Gene has cirrhosis and when he takes Tylenol, he has a much different response to it than his wife. Which of the following is the most likely contributing factor to this difference in response?

Question 19 options:

1)

Body size

2)

Stomach contents

3)

Liver enzyme activity

4)

Health status

Carbohydrate intolerance is a rare but very serious hereditary disorder. Cases due to lack of digestive enzyme and to impaired hexose transport have been reported. It is estimated that glucose-galactose malabsorption accounts for 2% of the patients with protracted diarrhea of infancy. In two reported cases of glucose-galactose malabsorption, the infants developed diarrhea soon after birth. Their stools contained reducing sugars and had an acidic pH. Analysis of tissue obtained by biopsy of the small intestine showed normal villi with normal disaccharidase values. Monosaccharide feeding (loading) tests showed a normal rise in blood glucose following a fructose load dose, which was tolerated well. This result was in contrast to a flat glucose curve in response to a glucose load, which was accompanied by marked abdominal distension, profuse diarrhea, and the presence of reducing sugars in the stools.

What is a reducing sugar? Why would it be increased in these patients?

Which monosaccharide transport protein is lacking in these patients? Give a rationale for your answer.

If the plasma glucose concentration had been monitored in these two patients following a load of sucrose, would a rise in plasma glucose have been observed? Give a rationale for your answer.

In terms of plasma glucose concentration, what would have been observed following a loading dose of lactose?

What would be an appropriate dietary treatment for these individuals?

59. If "O" is the gene for the color of a carrot, and "OO" is the written form of the genotype, what is the genotype? a. orange b. heterozygous dominant c. homozygous recessive d. homozygous dominant e. heterozygous recessive

When you pour salt on a snail or slug, they begin to shrivel up and die while excreting a bubbly mucus around themselves, what process best describes what is happening to the snail? a. Osmosis b. Endocytosis c. Passive Facilitated Diffusion d. Passive Simple Diffusion e. Active Transport

What attracts or directs the synthesis enzyme to the template in Transcription? a. Promoter b. 5'-cap c. Poly-A Tail d. Start Codon e. Primer

Thinking of the various molecules that make up a biological membrane, the nature of which molecule specifically provides membranes with its unique structure (the bilipid layer)? a. proteins b. phospholipids c. carbohydrates d. cholesterol e. cellulose

70. Why is the cytoskeleton and ribosomes characterized as cellular structures rather than organelles? a. they lack a cell wall b. they lack a nucleus c. they lack a biological membrane d. they are characterized as vacuoles, not structures e. they lack nucleotides

73. Which of the following is NOT a function of cellular membranes? a. regulate transport of a solute b. localize function c. define compartments d. mediate cell-to-cell communication e. locomotion

Study 4

In a study of people with Hypertension, 65,000 people with hypertension were followed for 5 years. All were screened negative for Parkinson’s diseases (PD) when they entered the study. To control their hypertension the population was taking either calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). 25,000 people were taking CCBs, 20,000 were taking ACEIs and 20,000 were taking ARBs. This study wanted to look at the exposure to CCBs and ARBs and if it led to PD. The incidence of PD in those taking CCBs was 27/1000 and the incidence for those taking ARBs was 22/1,000.

Label the table and fill it in.

1. What type of study is this?

a. cross-sectional

b. case report/series

c. ecologic

d. case-control

e. cohort

f. clinical trial

g. community intervention

2. What is the most appropriate measure of association?

a. odd ratio

b. relative risk

c. Attributable risk

d. none of these

3. Calculate the measure of association (use two decimal places).

4. How would you best describe the relationship between the exposure and the outcome?

a. no relationship

b. positive relationship

c. negative relationship

5. If appropriate, calculate the attributable risk per 1000 people (use 2 decimal places).

***would you mind showing all of your work? Thank you!

You have discovered a new virus that contains only RNA as its genetic material. Curious as to how this virus works, you infect host cells with this virus and discover that after infection, the host cell makes lots of viral RNA molecules and various viral proteins. Upon further examination, you discover that the viral genome has been inserted into the host genome as DNA.

These are the steps of the information flow for this virus. Each arrow represents a process that is carried out by an enzyme.

RNA viral genome --> DNA --> RNA --> protein
Considering an actively-dividing, normal cell that carries the viral genome, indicate

whether the following statements are true or false for the virus discussed above.

You do NOT need to give reasoning or justification for your answer. Just answer true or false in your answer booklet.

Answer A, B, C, and D

A) RNA-dependent RNA polymerase is used at some point during the viral life cycle to copy the viral genome. (1.5 marks)

B) The polymerase used by the virus to copy its genome forms a covalent bond between a 5? phosphate and a 3? hydroxyl. (1.5 marks)

C) During copying of the viral genome, polymerization would proceed in the 3? --> 5?direction. (1.5 marks)

D) Deoxyribonucleotides would be incorporated into the viral genome that is inserted into the host chromosome.

Hepatitis C is a chronic liver infection that can be either silent (with no noticeable symptoms) or debilitating. Either way, 80% of infected persons experience continuing liver destruction. Chronic hepatitis C infection is the leading cause of liver transplants in the United States. The virus that causes it is blood borne, and therefore patients who undergo frequent procedures involving transfer of blood are particularly susceptible to infection. Kidney dialysis patients belong to this group. In 2008, a for-profit hemodialysis facility in New York was shut down after nine of its patients were confirmed as having become infected with hepatitis C while undergoing hemodialysis treatments there between 2001 and 2008.

When the investigation was conducted in 2008, investigators found that 20 of the facility’s 162 patients had been documented with hepatitis C infection at the time they began their association with the clinic. All the current patients were then offered hepatitis C testing, to determine how many had acquired hepatitis C during the time they were receiving treatment at the clinic. They were considered positive if enzyme-linked immunosorbent assay (ELISA) tests showed the presence of antibodies to the hepatitis C virus.

Health officials did not test the workers at the hemodialysis facility for hepatitis C because they did not view them as likely sources of the nine new infections. Why not?

Why do you think patients were tested for antibody to the virus instead of for the presence of the virus itself