In a follow-up to its April 10 letter, Public Citizen has informed HHS Secretary Sebelius that at least 4,500 extremely vulnerable, premature babies are being sought for enrollment in 7 publicly funded experiments whose purpose, protocol design, ethical foundation and risk of death, are of concern.

The newly uncovered experiments on NIH’s website–are being conducted by the same National Research Network whose oxygen SUPPORT experiment has been found in gross violation of Federal research standards.

The primary endpoint of the newly uncovered current experiments involving premature infantsis  listed as “death or severe disability.”  That is an indication that the experiment is NOT designed to improve infants’ survival chances.   

(1) Evaluation of Systemic Hypothermia Initiated After 6 Hours of Age in Infants ≥ 36 Weeks Gestation With Hypoxic-Ischemic Encephalopathy: A Bayesian Evaluation (primary endpoints: death or moderate or severe disability);
http://clinicaltrials.gov/ct2/show/NCT00614744

(2) A Multi-center Randomized Trial of Laparotomy vs. Drainage as the Initial Surgical Therapy for Extremely Low Birth Weight Infants With Necrotizing Enterocolitis or Isolated Intestinal Perforation (primary endpoints: death or neurodevelopmental impairment); http://clinicaltrials.gov/ct2/show/NCT01029353

(3) Optimizing Cooling Strategies at < 6 Hours of Age for Neonatal Hypoxic-Ischemic Encephalopathy (primary endpoints: death or moderate to severe disability); http://clinicaltrials.gov/ct2/show/NCT01192776

(4) A Randomized Controlled Trial of the Effect of Hydrocortisone on Survival Without Bronchopulmonary Dysplasia and on Neurodevelopmental Outcomes at 22-26 Months of Age in Intubated Infants < 30 Weeks Gestation Age (primary endpoints: improvement in survival without physiologically defined moderate to severe bronchopulmonary dysplasia, and survival without moderate or severe neurodevelopmental impairment); http://clinicaltrials.gov/ct2/show/NCT01353313

(5) Neurodevelopmental Effects of Donor Human Milk vs. Preterm Formula in Extremely Low Birth Weight Infants (primary endpoint: neurodevelopmental outcome; death is one of the secondary endpoints); http://clinicaltrials.gov/ct2/show/NCT01534481

(6) Transfusion of Prematures (TOP) Trial: Does a Liberal Red Blood Cell Transfusion Strategy Improve Neurologically-Intact Survival of Extremely-Low-Birth-Weight Infants as Compared to Restrictive Strategy? (primary endpoints: death or significant neurodevelopmental impairment);
http://clinicaltrials.gov/ct2/show/NCT01702805

(7) A Randomized Trial of Targeted Temperature Management with Whole Body Hypothermia for Moderate and Severe Hypoxic-Ischemic Encephalopathy in Premature Infants 33-35 Weeks Gestational Age (primary endpoints: death or moderate or severe disability). http://clinicaltrials.gov/ct2/show/NCT01793129

(1) Make publicly available on the HHS website all versions of the protocols, sample consent forms and institutional review board-approved consent forms for ongoing clinical trials involving infants being conducted by the Neonatal Research Network, as well as all prior clinical trials conducted by the network since 1986, so that they can be independently assessed by ethicists, researchers, patient advocates and the general public; and

(2) Order the suspension of new enrollment in the ongoing clinical trials until HHS receives confirmation from independent experts that the protocol, consent form content and plan for obtaining consent are adequate and appropriate.

The Alliance for Human Research Protection calls for disciplinary action to hold medical researchers and their academic institutions accountable for violations of Federal research protections.  If research was conducted in violation of Federal protections, resulting in preventable injury or deaths, the senior researchers involved should be ineligible to obtain public funding; their research privileges should be suspended for a probationary period during which they should enroll in medical ethics training. If ever they violate ethical / legal standards again, they should be banned from all research involving human subjects.

AHRP also calls for the revocation of the Federal licensure from academic institutions that have been the site of unethical medical research whose subjects suffered permanent injury or death—as happened in 2001 when Johns Hopkins University research license was suspended. http://www.hhs.gov/ohrp/detrm_letrs/jul01a.pdf

Vera Sharav

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Transfusion of Prematures (TOP) Trial: Does a Liberal Red Blood Cell TransfusionStrategy Improve Neurologically Intact Survival of Extremely Low Birth Weight Infants as Compa red to Restrictive Strategy?  ( primary endpoints: death or significant neurodevelopmental impairment)

This study is comparing two different strategies for treating anemia (low red blood cell count) in extremely premature infants (birth weightof less than 2.2 pounds).

 The infants are randomly divided into two groups. Babies in one group receive blood transfusions whenever their red blood cell counts are moderately low (“liberal” transfusion group), and babies in the other group will receive blood transfusions only when their red blood cell counts are severely low (“restricted” transfusion group). The researchers will then determine whether one group of babies has higher rates of death or long term neurologicdamage compared with the other group. The study began in December 2012 and is expected to continue until August 2017. The researchers plan to enroll more than 1,800 extremely premature babies.

Principal Investigator:             Michele C Walsh, MD               Case Western Reserve University, Rainbow Babies and Children’s Hospital

Principal Investigator:             Abhik Das, PhD                        RTI International

Principal Investigator:             Beena Sood, MD                       Wayne State University

Principal Investigator:             Abbot R Laptook, MD                Brown University, Women & Infants Hospital of Rhode Island

Principal Investigator:             Ron N Goldberg, MD                  Duke University

Principal Investigator:             Barbara J Stoll, MD                    Emory University

Principal Investigator:             Brenda B Poindexter, MD, MS          Indiana University

Principal Investigator:             Krisa P Van Meurs, MD               Stanford University

Principal Investigator:             Kurt Schibler, MD                       Cincinnati Children’s Medical Center

Principal Investigator:             Waldemar A Carlo, MD                   University of Alabama at Birmingham

Principal Investigator:             Kristi L Watterberg, MD                    University of New Mexico

Principal Investigator:             Pablo J Sanchez, MD                   University of Texas Southwestern Medical Center at Dallas

Principal Investigator:             Kathleen A Kennedy, MD, MPH      University of Texas Health Science Center, Houston

Principal Investigator:             Carl T D’Angio, MD                           University of Rochester

Principal Investigator:             Leif Nelin, MD                                Research Institute at Nationwide Children’s Hospital

Principal Investigator:             William Truog, MD                          Children’s Mercy Hospital-Kansas City, MO

Principal Investigator:             Uday Devaskar, MD                        University of California, Los Angeles

Study Director:           Haresh M Kirpalani, MD                             University of Pennsylvania

Clinicaltrials.gov: http://clinicaltrials.gov/ct2/show/NCT01702805