- 先日の記事でNGSデータから得られた情報の扱いについて書いたけれど、その姉妹編(今日の記事が本編化)
- ゲノム研究参加者への情報伝達について(The Clinical Sequencing Exploratory Research (CSER) Consortium and the Electronic Medical Records and Genomics (eMERGE) Network](Return of Genomic Results to Research Participants: The Floor, the Ceiling, and the Choices In Between)
- Guiding Principles(５原則)
- 1 研究(臨床研究を含む)は実臨床とは違うので、返却する情報に違いがあるかもしれない
- 2 研究目的の場合、actionable(結果がわかったら対応しようのあるよう)な遺伝情報を網羅することは研究者に求める必要はない
- 3 何を返すべきか、何は返さなくてもよいか、返さないべきか、は、研究の場合、臨床の場合のそれぞれで、「アウトカム」がどうなるかについて研究をしないとわからないから、そのような研究をするべきである
- 4 重要かつactionableであることが、analytically(データ解析上)も臨床上も確かな情報ならば、返すべき
- 5 結果を知らされない権利、知りたくないがために参加しないことなどをあらかじめインフォームド・コンセントする
- 原文(引用)
Principle 1: Research, even in a clinical setting, differs from clinical care in both its goals and its procedures; as a result, the minimal and maximal information returned in a research setting might differ from standards of clinical practice.
Principle 2: Resources for research should be primarily directed at scientific discovery; thus, researchers do not have a duty to look for actionable genomic findings beyond those uncovered in the normal process of their investigations.
Principle 3: Research assessing the outcomes of a wide range of potential practices for returning genomic results is required for the ultimate formulation of best practices in both the research and the clinical settings.
Principle 4: Analytically and clinically valid information that is of an important and actionable medical nature and that is identified as part of the research process should be offered to a research participant.
Principle 5: Participants should have the right to refuse any results that are offered. Potential research participants or parents of minors eligible for research studies should be provided proper informed consent that respects autonomy, including the right to refuse participation in research. If the return of results is essential to the purpose of the study, potential participants should be adequately informed at the time of recruitment so they are able to decline participation if they do not want to receive results and should be reminded of their right to withdraw prior to any return of results.
- 推奨
- 1 研究ターゲットそのもの、または、たまたま見つけた「重要な」遺伝情報を返却する。「既知の『重要な』遺伝情報を網羅的に調べること」は研究者には求めない
- a ここで「既知リスト」が問題になるが、その最低ラインの参考は、先日の記事の56遺伝子か
- b 研究実行中(fundedの期間)であって、連絡がとれる範囲でよい
- 2 返却されないでいる権利は研究参加時に保証する
- a 知りたくないのに知りそうになる事態が予想されるなら、その直前にスタディから抜けられるような方策も立てておく
- b 初期同意説明時にはわかっていなかったような遺伝情報が後に分かる可能性もあり、そんなときに連絡をされたいかの確認をし、また、そんなときに返却されないでいる権利も保証する
- c 研究参加者の判断はあくまでも尊重されるべきであってcoerctive(高圧的)であってはならない
- d 小児が対象であるとき、親子・トリオでの参加のときなどの特別な配慮も
- 3 シークエンシングの結果全部を返す(それを返却の天井ceilingと呼ぶ)こともある(床ライン floorは返却内容としての最低ライン)こともある
- a 返すことが利益の場合もあるけれど不利益になるかもしれないことにも留意する
- b 検体取り違えなどの可能性もあることに鑑み、Clinical Laboratory Improvement Amendment(CLIA)を完全に満足することはできないにしろ、その精度保証のための方向で努力することが必要
- c 返却について研究するときは、利益・害を測る指標について含める必要がある
- 4 ゲノム情報の返却とその利益・害とに関する研究それ自体は、昨今のゲノムをめぐる状況から、すすめていく必要がある
- 原文
Consensus Recommendations
1.
At a minimum (the “floor”), researchers should offer individual genomic research results that are valid, medically important, and actionable if discovered purposefully or by chance during the course of data analysis. Investigators are not obligated to search for actionable genomic variants to be returned beyond those identified in the course of their research, that is, there is no duty to hunt.
a.
Given that there is no definitive “list” of medically actionable findings with respect to the return of research results and incidental findings and that such a list would be context dependent, those involved in genomics research should give thought to the types of findings that would represent the “floor” for return in their study in consultation with local IRBs and funding agencies. The ACMG list, currently containing 56 genes, is a reasonable starting point for consideration;1 however, more comprehensive lists have been offered.
b.
The responsibility to offer disclosure of results and incidental findings is limited to circumstances in which there are identifiable participants and to the period of funding to investigators, although investigators may elect to offer disclosure after that term.
2.
Participants should have the option to refuse research genomic test results, both those related to the study purpose and those that are incidental findings, unless the study aims are related to the return of these data. Plans for return and the participants’ option to refuse offered results should be addressed at the time of consent.
a.
When studies do not allow participants to opt out of potentially receiving results, this and the opportunity to withdraw prior to receiving results should be clearly addressed in the consent process and form.
b.
The consent process and form should clarify the circumstances in which a participant might be contacted in the future and explicitly ask whether the participant consents to future contact if new findings are found. Participants who are contacted regarding such results should have the right to decline receiving those results.
c.
Participation in research studies should be noncoercive and respectful of participant choice.
d.
Parents of minors participating in genomic research should generally have the same right to refuse, unless the return of the results is of high health significance to the minor in childhood. Investigators may reasonably offer the parents of minors participating in pediatric research the option of accepting or refusing results for adult-onset conditions along with counseling on the implications for the child’s best interests and the parents’ health status. In the case of trio testing, parents may be offered only their own adult-onset results and not their child’s, unless the child has a relevant de novo mutation.
3.
Researchers might be ethically and scientifically justified in returning all genomic information (the “ceiling”) in some format and any level of information in between the “floor” of actionable results identified during the course of research and the “ceiling” of all genomic information.
a.
Special care should be taken when the benefits and harms of returning a particular type of genomic information are uncertain.
b.
Investigators should take steps to assure adequate analytic and clinical validity for return, including systems to avoid sample mix-up. Further work is needed on the role of CLIA compliance in the return of research results.
c.
Research studies intended to examine practices for the return of genomic information should include measurements of benefits and harms in the design of the study.
4.
Additional research projects that examine the potential benefits and harms of receiving genomic results and evaluate practices for returning genomic information are required to inform the increasing use of genomic sequencing in clinical research.
