Document 995G7NVMdzk252dBQZq8LKy6V

Draft Ethics Considerations and Status of Resolution Issue Resolution Scientific Validity of the Study Multiple review of protocols by an independent scientific review committee Approval of protocols by US and Chinese Universities' Institutional Review Boards Protocol changes to be approved by independent scientific review committee Benefits to Participants Improved diagnosis of disease Increased follow-up after treatment I think the improved workplace Can we really assure this? Isn't it in the hands of the monitoring and early diagnosis are potential long-term benefits to the Chinese? Improved workplace monitoring Are we actually "improving" or are we using the Chinese (and other) population after the CDC data? I did not think that the study was going study and not necessarily to the into the worksplace, but that the participants were participants themselves coming via referall from hospital diagnosis. Early diagnosis of benzene toxicity and removal from workplace ONLY if participant goes to the doctor and are diagnosed. Monetary compensation Appropriateness of Compensation to Compensation to be based upon level of participation and, Participants to avoid excessive inducement, standard practice in China (and US??) for similar procedures. Informed Consent Confidentiality Consent forms tailored to type of participation in the study and disease status, e.g., case or control. Forms to be developed with input of Chinese clinicians and bioethicist. Forms reviewed by an independant review board. Separate password controlled databases for clinical and study-specific research data. Transfer of data ootwe-en from clinical to study databases requires consent of participant. Your Comments and Questions February 13,2001 SH ELL-MCCLU RG-065530 Culturally Sensitive Questionnaire & History Control of Results Questionnaire to determine occupational history and lifestyle information will be developed with input of local Chinese researchers and Chinese bioethicist. Questionaires reviewed by an independant review board. Independent Scientific Review Committee will review proposed abstracts of presentations and manuscripts for publication. The investigators will have final control over content and interpretation of published or presented study data Benefits to the General Worker A committee of the eentml provisional government Population Exposed to Benzene believes it can use the molecular epidemiology study to justify a lower benzene occupational exposure standard. Identification of more sensitive biological indicators of exeessicve exposure to benzene How would you define excessive? I thought determining exposure/effect was part of the purpose of this study. Other Benefits State of the art diagnostic laboratory will remain in Shanghai for future use. Technology transfer from training of local laboratory technicians Possible increase in level of hematopoietic disease diagnosis and care after exposure to US study procedures Technology transfer from high quality industrial hygiene monitoring technology & practices Identification of other unknown benzene Data immediately reviewed and reported to EPA under effects TSCA 8(e) February 13,2001 SH ELL-MCCLU RG-065531 Q&A Studies of Benzene in China Page 1 The purpose of this document is to outline the answers to the questions most frequently asked regarding these studies. Glossary of Terms AML (Acute Myelogenous Leukemia): The hematopoietic cancer most commonly associated with exposure to benzene. Hematopoiesis: The formation of blood and blood cells, including red & white blood cells and platelets. NHL (Non-Hodgkins Lymphoma): Complex spectrum of malignancies oflymphoid tissues, most often arising in the lymph nodes. NCIICAPM (National Cancer Institue/Chinese Academy of Preventative Medicine) - The authors of a previous set of studies in China that found NHL associated with benzene exposure, the first study to show such a linkage. SMCDC (Shanghai Municipal Centers for Disease Control) - The Shanghai governmental agency responsible for occupational exposure monitoring and enforcement // /' c/ /1/''-. Q. For the Case Contr~(Stud~f~(, w!lY ~/ \",. techniques. A number of viral infections are just perform a retro~ective stUdy; )V6u)tfthat/'-. \fnown risk factors for some forms ofNHL. For not be a quicke~ and nht.~~_le!.px(eJlsfve wif' ,xample, hepatitis C which is common in C?in~. to get the same mformatlOn~ / / / /" ... j / / The presence of the planned laboratory on sIte In // // ) ~ / / Shagg~ai assures us of consistent, state-of-the-art A. First and foremost, is the lack~f %mpite a1Q-~" ~1:rlgnosnc capabilities under our control without verifiable study. A diagnoses nUI?b~r of from o~h~r acosinmdpiY.tieorne(tc1aosnprei~~tt'~;:I~~, ./ . J//./j/tti!,Iiegn~ea?,r-(esietyn;.o,afiltehde logistic and bureaucratic in shipping human tissue ~, ~nd mIsd~agnosI~ IS easy In the~~ce ~f ~. / s;mples t9'tllei{S for testIng. /< "'.SophIstIcated dIagn~stic proce?ures: ~...<l}<).8~C 1\ / . samples are not routInely kept In ChIna ana the~. / / W~t5eheve--\hat th~'fJCI/CAPM study findIng of would be no opportunity to confirm diagnosesJO'r . Ah'creas4ris~.~f~ in benzene exposed most cases. Secondly, assessment of exposure'\. ./v// w9\kers ~due ~re~~nized confounding and confounding risk factors is complicated in aV {/ /fuctOrs. We do 11-ot want 'to repeat their mistake. retrospective study. In the case of deceased \ // '-./ //' \. patients, details of lifestyle and work history must Q. Why are w~iliclud~ A~ in the Case- be obtained from relatives or other workers. !a~ing cases prospectively reduc~s the distance Control"sfudy.A1\1:L )S'(Jso in the Disease Prorsi09-"sfudy. Isn't this a duplication? In tIme that one needs to go back In order to get (// needed exposure records. A. Incl-wiihg AML, which we would expect to see associated with benzene exposure, provides a Q. The diagnostic laboratory is a major expense. positive control to defend against criticisms that Why is it necessary? Why can't we just do a our methodology was somehow not adequate to standard case-control study? see associations that do exist. There is some overlap in that the Case-Control study will serve A. Non Hodgkin's Lymphoma (NHL) is an as one source of AML cases in the Disease aggregate category of ca. 20 distinct lymphocytic Progression study. diseases. In order to perform an NHL study that conforms with the current diagnostic schema, the subtype ofNHL should be known. These subtypes are distinguished by morphological appearance and characterization of cell surface markers by sophisticated immunochemical February 16,2001 SH ELL-MCCLU RG-065532 Q&A Studies of Benzene in China Page 2 Q. One of the reasons for pursuing the Molecular complicate obtaining large numbers of Epidemiology study is that the Chinese participants. officials in Shanghai have requested this type Bioethics - Providing this higher level of of data; why can't they use the existing diagnostic information to hospital physicians NCIICAPM study results? improves the level of patient care which fulfills the ethical requirement that the study benefit The NCIICAPM study was roundly criticized for participants and the general community in which not providing a good measure of actual exposure; the research is performed. for not accounting for exposures to multiple chemicals; for assuming that all AML, NHL, and eoxthpeorsbulroeotdo-breelnazteednediasleoansee;sawnderwe ictahu~serd/bs.~t114y Q. If the Chinese are going to be the major beneficiaries of this research, shouldn't they contribute to the project? design that did not account for cog:founding \\ factors (e.g, smoking) and oth~l'actor,o/.'t{SEP~ A. Although the Chinese are not providing direct has taken the position that thiS stuQ,y'{annbt be / monetary contributions, they will be contributing used to calculate a qu'>.~tiv)<~{nceJ~F?sk f~ / / '\.\ in-kind s~pport. The labora~ory space allocated benzene exposure. ~IS IS P~Is~ly'the roy \. to the project has been provIded by Fudan this study will be so ii1wortanC~ /// / / //'\. <. . ~...___~</// , / / \University. The funds provided by API for the )aboratory space ha.ve gone toward renovation of The ChInese base theIr occupatIOnal' stan~ards o n / / that space to make It acceptable for the purposes measurable effects on people, .sure(not)Mi ) / // of tlJj.8'~tudy, but we will not pay any rent for the mathematical modeling of hyp'6th~r6al isks iSIs' -se of t~ space during the period of our studies. typical in the U.S. and Europe. the 1)fCIICPM 1)1e co}isiderable resources of the Shanghai .studies d~d not rovide them :vith t. .t o! a ,-/jMu%,ipal C~Rters for Di~ease ~ontrol (SMC~C) upon whIch to base a change In theIr b~t ~. / h e bee ffet< d freel ,IncludIng use of theIr standards. Their current standard is bas''e,q ~ty, atabC}.8(to identj{~ facilities and individuals to decrease in white blood cell counts ratherYhan \. / . inchlde i~.th,e studY'\as well as laboratory support leukemia. They are interested in the MoleculaV . /~r ind~trial~~\t~IOnitoring analyses Epidemiology Study which is intended to proVipe / ne~ssari'{.o the,..study. ''l\\nd most pointedly, the an objective, measurable indicator of risk. v{ .A:hin'e.se"movide\ccess t6'{he subjects, without .\.. / / whom'it wouldylimpossib~to conduct such a Q. Why are we taking on the expense of providing study. / / /\.. / laboratory diagnostic services for hematopoietic diseases in Shanghai hospitals / / / / / \..-.// Q. WhJA{thi~l(eing undertaken primarily by the during the course of the study? pdroley,nf industry, and why have other indltS6ies and/or international companies not A. These services provide crucial benefits to the been approached to help fund this research? consortium research in two areas: Research Data - As the central diagnostic A. API has played a lead role in getting this study laboratory we will assure the quality and underway, because the petroleum industry has a consistency of the diagnostic data. This role major interest in better understanding risks to assures access to blood and bone marrow samples human health due to benzene exposure. Other from study participants. Without this role we industries are being approached to help in this would have to seek permission to perform a effort, as are international petroleum companies second procedure to obtain these tissues for the and trade associations. Presentations have been research. Patients would be reluctant to undergo made to CONCAWE, IPIECA, and CEFIC. At such a second procedure, which would least one of our major supporters, BP, is headquartered outside the United States. For more information contact: Lorraine Twerdok (API) at (202)682-8344 or twerdokl@api.org; or Patrick Beatty (Chevron) at (510)242-7037 or pwbe@chevron.com February 16,2001 SH ELL-MCCLU RG-065533