Resuscitation Research and the Final Rule: Is There an Impasse?

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bound child at the start and end of the Head Start year.

NRS became an instant controversy. The test in-strument was designed hurriedly by appointed con-tractors who did not have time to establish reliability and validity using accepted procedures. In the field, personnel quickly raised questions about culture fairness and age appropriateness of test items. Huge variations in the abilities and training of test admin-istrators became evident. Fears were expressed about the impact of the testing experience itself on such young children early in their transition to school.

Beyond the psychometric and practical issues, trepidation over the NRS arose because the purpose of the evaluation was never made clear. The diffi-culty level of the test and the lack of funding for examiners and even postage to return the results led many to see the NRS as an effort to label centers as poor performers and stop their grants. Another un-fortunate consequence is that many teachers began to rewrite lesson plans to “teach to the test,” reducing time spent on health, nutrition, and social learning because these areas were not covered by the NRS. In essence, they thought that Head Start’s mission had been changed without anyone telling them. Addi-tionally, there was no hint how the NRS fit into the numerous other local and national assessments un-derway. The established protocols were in place to monitor and improve program quality and child out-comes. There was no explanation of value added by test scores of individual children on a narrow slice of skills targeted by Head Start.

Opposition to the NRS snowballed. Editorials de-nouncing the program appeared all over the country. More than 250 scholars signed a letter to US Senators questioning the structure, fairness, and purpose of the test. Our own responses focused on the fact that the NRS does not begin to assess the program known as Head Start. The Head Start that is delivered in nearly 50 000 classrooms in the states, territories, and tribal nations consists of comprehensive, two-gener-ation services designed to promote physical, cogni-tive, and socioemotional development, all necessary elements of school readiness. The NRS is concerned only with cognitive achievements and skills, as if they alone define what it means to be prepared for school.

No reasoned criticism of the NRS has denied the need for accountability. Head Start consumes billions of public dollars annually and should demonstrate that participants get what they came for: the skills that make them ready for school. The National Im-pact Study and the Child Outcomes Framework are both underway for this very purpose. To their credit, Head Start’s administrators have listened to the con-cerns of their critics and input that has poured in from the field. We sense that they now consider the NRS a work in progress.

The first nationwide administration of the NRS alerted Head Start officials to what they need to do differently. They have discovered that there are pit-falls in attempting to test hundreds of thousands of young children and train tens of thousands of exam-iners and that it is important to work with Head Start

providers to launch a new directive. Wade Horn, the current Assistant Secretary of the Administration for Children and Families, has now stated that the NRS is “incomplete” and must be redesigned to incorpo-rate measures of social and emotional development.4

Tommy Thompson, current Secretary of the Depart-ment of Health and Human Services, announced plans to appoint an independent panel of experts to review the first implementation of the NRS and rec-ommend improvements.

We are confident that if Head Start officials rely on the expertise that already exists in this area and build on the considerable work that has been done already to develop scientifically based protocols, the NRS can become a credible, useful means of helping Head Start providers deliver better services that enable Head Start children to be better prepared for school.

Edward Zigler, PhD Sally J. Styfco, BA

Yale Center in Child Development and Social Policy Yale University

New Haven, CT 06511

REFERENCES

1. Head Start Bureau.Charting Our Progress: Development of the Head Start Program Performance Measures. Washington, DC: Administration on Chil-dren, Youth and Families; 1995

2. Administration for Children and Families.Head Start FACES 2000: A Whole-Child Perspective on Program Performance.Washington, DC: Admin-istration for Children and Families; 2003

3. Advisory Committee on Head Start Research and Evaluation.Evaluating Head Start: A Recommended Framework for Studying the Impact of the Head Start Program. Washington, DC: US Department of Health and Human Services; 1999

4. Jacobson, L. Debate continues over Head Start assessment.Editorial Proj Educ Educ Week.2004;23(26):10

Resuscitation Research and the

Final Rule: Is There an Impasse?

ABBREVIATIONS. CA, cardiopulmonary arrest with apnea and loss of palpable pulse; RCT, randomized, clinical trial; IRB, insti-tutional review board.

C

ardiopulmonary arrest with apnea and loss of palpable pulse (CA) in childhood is a tragic event that often results in either death or poor-quality neurologic survival. This is especially true of CAs occurring in the out-of-hospital setting, where devastating neurologic injury is very com-mon. Until very recently, no therapy had been estab-lished to improve neurologic outcome in humans. Two randomized, clinical trials (RCTs) in highly se-lected adult populations with out-of-hospital CAs

Accepted for publication Jul 21, 2004. DOI: 10.1542/peds.2004-1458

Address correspondence to Frank W. Moler, MD, MS, Department of Pe-diatrics, University of Michigan, Ann Arbor, MI 48109-0243. E-mail: [email protected]

COMMENTARIES 859

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reported increased survival and, most importantly, improved neurologic outcomes.1,2 _{An expert}

com-mittee concluded that generalization of these find-ings to all adult or to pediatric CA events should not occur without additional study.3

Unfortunately, major advances in resuscitation of humans have been quite limited over the past 4 decades. The need for RCTs to advance resuscitation science is entering an important period. Promising therapies such as mild hypothermia and vasopressin have been reported recently to improve outcomes in very select adult CA populations.1,2,4 _However,

many critical questions remain that need urgent study. For example, concerning hypothermia: 1) What is the optimal temperature for therapeutic hy-pothermia? Does it vary by age group or etiology of CA? 2) What is the duration of the therapeutic win-dow? Are there factors that affect this? 3) What is the optimal duration of hypothermia? No large-scale RCT has been conducted in the nonneonatal pediat-ric population, and there exists little information on which to make recommendations.

Morris et al5_{in this issue of}_Pediatrics_{do an}

excel-lent job and should receive praise for investigating a hypothetical hypothermia study requiring commu-nity consent and reviewing some of the difficult issues related to the use of the “Exception From Informed Consent Requirement for Emergency Re-search” (Final Rule or 21 CFR 50.24). The Final Rule has been reported to facilitate study of emergency interventions with therapeutic windows of ⬍6 hours.6_{Perhaps the most difficult task for}

investiga-tors associated with the Final Rule is the requirement of a community consultation. For their hypothermia after an in-hospital CA study with a hypothetical 30-minute window of efficacy, the authors report that the consensus for community consultation at their large academic center was to create focus groups, to have publicly displayed information in the form of brochures and posters, and to give a brief discussion with guardians in the immediate pos-tresuscitation period in which an opportunity to de-cline study participation would exist. This seems quite reasonable; however, in the actual setting of in-hospital CA, it may not always be feasible. Family members may not be available within 30 minutes to begin a therapeutic hypothermia-intervention dis-cussion. Similarly, study investigators may not be available to give a brief verbal-consent discussion, because they might be busy stabilizing the child who was just resuscitated. For patients with general care area CAs or patients with CAs shortly after pediatric intensive care unit admission, the public information may not have been seen, and the families may not be immediately available. A “mock” observational study to determine what proportion of in-hospital CA subjects could actually be enrolled at the author’s facility may provide additional useful information. The authors correctly point out that their plan for community consultation would not be suitable for out-of-hospital CAs, which represents the very group that is at greatest risk of death and poor neu-rologic outcome associated with CA and may have the most to benefit from a hypothermia intervention.

A different and more complex community-consulta-tion process would need to be conducted for these patients to participate in a hypothermia study.

Other important issues related to the Final Rule and a hypothermia-for-pediatric-CA trial exist re-lated to the need for multicenter participation to achieve adequate study sample size. In such a trial, each study site would have its own unique institu-tional review board (IRB) interpretation of the Final Rule. Each site would likely have different require-ments requested of the study investigators related to community consultation at their location.7_For

exam-ple, one center’s IRB might require investigators to obtain informed consent prospectively from all high-risk congenital heart disease surgery patients, be-cause this is an easily identified at-risk population in which consent could be obtained prospectively. An-other IRB may have different requirements. AnAn-other practical issue is that the IRB process would likely to be quite lengthy, because most IRBs are unfamiliar with the special requirements of the Final Rule. In fact, according to the authors,5_{who are}

knowledge-able on the subject, no pediatric RCT using the emer-gency waiver of informed consent has been per-formed in the United States since the requirements were established in 1996. A feasibility issue with the Final Rule is that its complex requirements would potentially add significant cost and months of delay in the conduct of important federally sponsored RCTs. It is unlikely in a multicenter RCT that site investigators would have enough protected time to go though the administratively complex and poten-tially costly process required of the Final Rule. Study funding may need to be secured a priori that would cover the investigator’s effort, the administrative support needed for documentation, and costs asso-ciated with community consultation. Additional is-sues have been systematically reviewed and com-mented on by Biros et al.8

The current Final Rule was a very carefully con-structed set of procedures to protect patients with life-threatening emergency conditions from research in which informed consent was not possible. How-ever, the observation that little emergency or resus-citation research without consent has been con-ducted in the United States since 1996 may suggest that some modifications are required. The recent trend of major CA studies being conducted outside the United States in Europe, Australia, and other locations,1,2,4,9_{with US coauthors on occasion,}9_may

be additional evidence of this. Furthermore, the “Ex-ception From Informed Consent Requirement for Emergency Research” regulations have been identi-fied as one of the major barriers to research in the current National EMS Research Agenda, and steps to address the identified issues have been outlined.10_A

thorough review of the existing Final Rule require-ments may be in order by the Food and Drug Ad-ministration, Office for Human Research Protections, and ultimately Congress that would both continue to rigorously protect study subjects while at the same time permitting highly important research related to resuscitation to be conducted in the United States in a timely manner. Ideas such as creating a national

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IRB that leads the way in approving up front this uncommon, highly specialized high-risk/high-re-turn research followed by local IRB review with modification as needed could be one of many start-ing points for discussion.

Frank W. Moler, MD, MS

Department of Pediatrics University of Michigan Ann Arbor, MI 48109-0243

REFERENCES

1. The Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest.

N Engl J Med.2002;346:549 –556

2. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med.2002;346:557–563

3. Nolan JP, Morley PT, Vanden Hoek TL, et al. International Liaison Committee on Resuscitation. Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of

the International Liaison Committee on Resuscitation.Circulation.2003; 108:118 –121

4. Wenzel V, Krismer AC, Arntz HR, et al. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation.

N Engl J Med.2004;350:105–113

5. Morris MC, Nadkarni VM, Ward FR, Nelson RM. Exception from informed consent for pediatric resuscitation research: community con-sultation for a trial of brain cooling after in-hospital cardiac arrest.

Pediatrics.2004;114:776 –781

6. Clifton GL, Knudson P, McDonald M. Waiver of consent in studies of acute brain injury.J Neurotrauma.2002;19:1121–1126

7. Alpert S. Implementing the Final Rule [commentary].Acad Emerg Med.

1999;6:1188 –1189

8. Biros MH, Fish SS, Lewis RJ. Implementing the Food and Drug Admin-istration’s Final Rule for waiver of informed consent in certain emer-gency research circumstances.Acad Emerg Med.1999;6:1272–1282 9. Beatriz M, Perondi M, Reis AG, et al. A comparison of high-dose and

standard-dose epinephrine in children with cardiac arrest.N Engl J Med.

2004;350:1722–1730

10. National EMS Research Agenda. Available at: www.nhtsa.dot.gov/ people/injury/ems/EMS03-ResearchAgenda/home.htm. Accessed July 2, 2004

END OF THE AMERICAN DREAM?

”A classic 1978 survey found that among adult men whose fathers were in the bottom 25 percent of the population as ranked by social and economic status, 23 percent had made it into the top 25 percent. In other words, during the first 30 years or so after World War II, the American dream of upward mobility was a real experience for many people. . . . A new survey of today’s adult men finds that this number has dropped to only 10 percent.“

Krugman P.Nation.January 5, 2004

Submitted by Student

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DOI: 10.1542/peds.2004-1458

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Resuscitation Research and the Final Rule: Is There an Impasse?

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