BIO-BANKING

BARTHA MARIA KNOPPERS and MADELAINE SAGINUR

PRESENTED BY:REETIKA NEGI

WHAT IS BIO-BANKING ?• Biobanking can be described as "a large-scale collection of human biological

material", it may also refer to smaller collections of tissue (pathology paraffin blocks, biological fluids such as blood and urine, surgically removed "waste" tissue, and so on) stored in diagnostic departments, not with the primary aim of conducting research, but rather, of informing treatment .

• Samples and data stored by the pharmaceutical industry that have a potential for commercial gain would also constitute a biobank . In addition, the medical, genealogical and lifestyle-related data linked with the biological samples are considered a part of the biobank and are as important as the samples .

• Residual samples from earlier clinical trials or research studies stored as formal or informal collections in an individual researcher's freezer would also constitute a biobank .

• The other terms in use for a human tissue biobank are "biorepository", "biolibrary" and "biospecimen resource"

CASE STUDIES• For many years, physicians at a cancer clinic have been storing

biological samples left over after being used for diagnosis in clinical testing. Prior to 2000, no consent for storage or research was obtained. In 2000, the clinic changed its policy and began to systematically request consent for the use and storage of leftover biological samples ‘‘for future cancer research.’’ From that point on, the clinic has been storing samples only when the patient consented. It discards samples when the patient does not consent. Many of the sample donors are still alive (some are still patients at the clinic), while others have died. The clinic now has over 4000 samples, with comprehensive clinical data. Two groups of geneticists would like to use the samples for research, one examining the genetic basis of certain cancers, and the other examining the genetic basis of ethnicity and drug response in a randomized, heterogeneous population study.

HeLa IMMORTAL CELL LINEHenrietta Lacks was an Afro-American woman who died of cervical cancer in 1951. She was source of cells which were cultured by Dr. George Otto Gey to create the first known human immortal cell line for medical research, which now is known as the HeLa cell line. During her treatment , two samples of Henrietta’s cervix removed– a healthy part and a cancerous part---without her permission.The cell culture from her tumor could be kept alive and grew indefinitely, the cell line so developed was used in a large number of researches and experiments including Salk’s Polio Vaccine, AIDS, cancer, gene mapping, radiation effect etc.However, the Lacks family was kept in dark about the existence of this immortal cell line, and got to know about it after over 25 years of her death when related articles was published in March 1976.

WHY IS BIO-BANKING IMPORTANT AND ATTRACTIVE?

• Newer technologies have not just enabled us to analyze biological materials in greater details but enabled us to handle larger and more complex databases also, thus the quest to study diseases, conditions at the molecular level as well as to develop treatments including more and more personalized treatments has grown.

• There is a huge commercial potential in development of new drugs and treatment regimens associated with biobanking, which has resulted in a boom of biobank facilities whether they be governmental, joint-ventures or private ones.

• Bio-bank linked research findings can be helpful in assisting development of health policies and expenditures.

ETHICAL ISSUES

• There are several aspects with ethical implications involved with biobanking, despite the claims that bio-banking has no risks as it can do no harm to an individual’s body.

• CONSENTConsent is the most important aspect of biobanking. It is often argued that

explicit individual consent is not necessary as there in no possibility of physical harm to the contributor of the sample/data.

But this is a violation of the principles of autonomy and voluntariness as it undermines a person’s dignity, privacy and his contribution to medical research.

‘Informed consent’ is more of a misnomer here as it is not plausible to give complete details about the types of future uses of the samples and the possible researches/studies the sample might be used for

CONFIDENTIALITY AND ANONYMIZATION• One way of ensuring the individual's right to privacy and upholding the principle of

confidentiality is to minimise the connection between the identifiers and the stored sample or medical data, i.e. to delink the person from his/her biological material.There are several ways in which this can be done and to varying degrees:

• Identifiable- the person’s identity is directly attached with the sample• Traceable / coded or linked - A code is attached to the sample/data and the

correspondence between the code and the identity is physically separated. Only a few people are aware of the connection.

• Encrypted/double coded - The code is transformed into several characters by a third party. The third party will be required to trace the individual identity. (This method was in use in Iceland's deCODE biobank.)

• Anonymised or unlinked - The link between the samples/data and the individual identity is irreversibly cut. Therefore, they lack identifiers.

• Anonymous or unidentified – samples without identifiers from the start

CONFIDENTIALITY AND ANONYMIZATION

• But there are questions raised here too:

1. The question of the potential uses and abuse of the biological samples.

2. anonymisation frees the researcher from the obligation of communicating the results to the donor

3. this system of protecting identity results in the individual's loss of control over the sample being destroyed, or uncertainty over whether he/she will be informed about future research and the findings of the research, or whether he/she will receive a share of the benefits of the research

4. challenges arising from the large numbers handled in biobanks, multiple investigators handling datasets, the transfer of samples etc.

CONSENT

• There are a number of stages or possibilities for which consent might be required:

1. Storage2. interventions/tests on the sample3. the use of data linked to the sample4. whether or not one should be informed about the findings of

the research5. transfer of the sample/data to other investigators/institutions6. possible commercialisation and the possibility of deriving

financial benefit from the samples/data and all that this involves.

CONSENT• "Blanket consent" is the most general consent, with the participant not

knowing the specific purpose of the research. Some argue that this can hardly be considered consent .

• In the case of "presumed consent," the donor receives information on the details of the study, and if no response is received, it is considered "presumed" or "passive" consent . There is considerable debate on the extent to which passive consent meets ethical standards .It could also lead to anger and mistrust.

• The use of "broad consent" or "enlarged consent", has been proposed when the specific use of biological samples is not known but consent is sought for their future use, while providing a broad framework for their potential use .

• "Group consent" or "community consent" is another option, especially for genetic studies. Here, the possible outcomes and the scope of the work are discussed with the family/community before individual consent is obtained .

CONSENTOn the whole there is an increasing recognition of the validity of waiver of consent for

secondary research on double-coded specimens and data, and there is an increasing acceptability of broad consent for population projects.

Most international organizations and regional organizations like UNESCO, HUGO, CIOMS, WHO, the Council of Europe etc. advocate this approach but emphasize on the anonymization of data; approval by ethics committee and no objection on the side of the patient.

At national levels UK, USA, France, Canada, Germany do not require re-consent for anonymized data.

The ICMR guidelines(2006) provide that informed consent should be obtained from donors for DNA and cell line banking. Among the other requirements are that donors should be informed about the purpose, the conditions for the use of the sample by other researchers, how long the sample will be preserved and the costs involved in a researcher obtaining samples from the repository. In case there is a possibility of commercial prospects, the guidelines emphasise the need for "appropriate benefit-sharing agreements" signed by the donor, sample collector and "repository in charge."

COMMERCIALIZATION and OWNERSHIP RIGHTS

• Commercialization of obtained samples and data is related to the questions of dehumanizing/commodification of human biological material and is closely related to the issue of ownership rights.

• as the involvement of private companies into this field enhances public health system as well as makes better medical facilities a reality, it also makes them eligible to have an ownership right over the sample and data collected.

• On one hand it leads to the issue of sharing of data and intellectual property rights and as well as leads to questions of privacy and trust between the various stakeholders.

• It may skew research agenda in favor of research projects which are more profitable and compromise necessary but not profitable research.

COMMERCIALIZATION and OWNERSHIP RIGHTS

• The ICMR guidelines(2006) also states that due intellectual property rights should be given while granting access to samples, through a contractual agreement. But does not provide any further specification for the agreement

• The guidelines also state that for any publication resulting out of research from samples taken from repository, appropriate acknowledgement should be given to the original contributor of samples, sponsors of research, repository, donors and participants.

• The guidelines also states that there should be appropriate Material Transfer Agreements with the Repository for depositing samples as well as for taking them out with clear reasons. Third parties must be allowed to take samples only after approval from Repository ethics committee.

SHARING OF BENEFITS• Commercialisation also raises the issue of the sharing of benefits.• Article 19 of the UNESCO Declaration (2003) states that there are

multiple forms of benefit that include special assistance to persons/groups that participated in the research, access to medical care, provision of new diagnostics and facilities for new treatments or drugs stemming from the research, support for health services and capacity-building facilities for research purposes. Therefore, benefit goes beyond monetary or economic gain.

• A popular view is that direct benefit for contributors is not right as it could coerce people into participating and thus make them more vulnerable and also it goes against the concept of altruism, a major reason why people contribute.

• A number empirical studies suggest that a large number of people specially agree to such researches and donations with the hope of better medical aid in return.

BENEFIT SHARING• Also some may do out it out of a feeling of respect or

indebtedness to doctors, which reflects the unequal relationship between the patient and the health-service providers, specially in the Indian context. thus it is important to see what expectations does a contributor have in terms of benefits for himself and how are they fulfilled to maintain the trust between both parties

• A major question here is that how should benefits be accrued to a participant if the samples are anonymised or if the participant is not traceable

• The ICMR guidelines on DNA/cell line banking are explicit about benefit-sharing, stating that "if any commercial use of the samples in the repository is made, appropriate written benefit-sharing agreements, jointly signed by the donor, sample collector and the repository in-charge" should be made .

CASE STUDIES REVISITED• It is required that the interested geneticists firstly verify the conditions

under which the consent was obtained for sample collection. Did the consent include any information about extended or further uses of the collected sample? If so, were any specific uses described?

• In case of lack of specific consent for research purposes, a ‘broad consent’ may be assumed according to the governing guidelines for secondary uses of collected samples along with the approval of a ethics committee or IRB. For patients still living, re-consent should be taken.

• As the genetic variation and drug response study would require random data, including access to medical records, anonimyzation and removal of identifiers from selected charts and samples before use as such studies mostly publish aggregated results. if specific consent is required will again depend on the ethics board and the local laws. The anonimyzation, however, may rule out consent and waiver may be granted.

HeLa Case Study• Neither Lacks or her family had given consent for the preservation and

harvesting of the cells, or was any permission sought or required then. The discarded patient tissue was the property of the physician/medical institute. Her situation was discussed in the Supreme Court of California case of Moore vs. Regents of the University of California. On July 9, 1990, the court ruled that a person’s discarded tissue and cells are not their property and can be commercialized.

• Later the cells were commercialized. In 1980s family medical records were published without consent and in 2013, March , DNA code of a strain of HeLa cells was again published without consent.

• In August 2013, an agreement between the family and the National Institutes of Health was announced that gave family some control over access to the cell’s DNA code and a promise of acknowledgement in scientific papers. In addition, two family members will join a six-member committee which will regulate the access to the code.

RESEARCH RESULTS AND ASSESSMENT OF RESEARCH OUTCOMES

• Does the repository or researcher have exclusive right over the results of his work?

• If information has to shared to what extent do the details have to be shared?

• Is not making public the result of the research/study a breach of confidentiality?

• How does one assess the success of such research outcomes? And who does this assessment?

TRANSPLANTS• Transplantation of Human Organs Act, 1994’• Provides regulation for transplants from cadavers as

well as live donors, embryonic and foetal transplants…• Cadaver – in case of lack of will, next of kin have the

right to decide organ donation. Respect of dignity….in handling of the organs donated.. If samples used for any other purposes without explicit consent would be counted as violation.

• Live donors– principle of non-maliaficence i.e. donor interests are above that of the recipient. Legal capacity is essential, and so is free and voluntary consent

TRANSPLANTS• The donor should be at liberty to withdraw from the experiment

and to abrogate the consent given earlier, with no requirement to offer any explanation of the reasons.

• Any transplant involving embryonic or foetal tissue would require approval of the IC-SCRT as well as NAC-SCRT.

• No research is permitted on the live aborted foetus.• Tissue for transplantation or research may be obtained from dead

embryos or foetuses, their death resulting from legally induced or spontaneous abortion.

• Voluntary, informed, written consent will be obtained from the mother in two

• stages - first for the abortion, next for the donation of tissue from the foetus. The mother will not dictate who shall receive the foetal tissue taken for transplantation. Anonymity is to maintained on both sides

TRANSPLANTS• The procurement of embryos, foetuses or their tissue for

commercial purposes will not involve profit or remuneration.• Intact embryos or foetuses will not be kept alive artificially for

the purpose of removing usable material.• Tissues from aborted foetus can be cultured and banked for

use in research on transplantation.• umbilical cord blood from a live foetus or neonate for

transplantation The fundamental principle in any operation on a live foetus or neonate will be to ensure that no harm will occur to the baby….written informed consent by parents on behalf of parents

• Use of tissue or organs from dead anencephalic foetus or neonate (foetus or neonate lacking brain development above the level of the brainstem) is permitted.