Freeing archival research from the accidental and overbearing IRB regulation that costs human lives.

• Author: Briggs, William K.
• Position: Institutional review boards - VI. Costs of Regulation through VII. Conclusion, with footnotes, p. 270-315

4. COSTS OF REGULATION

   The value of archival research is obvious; it allows for otherwise impossible, life-saving discoveries in a cheap and harmless manner. (245) It is also clear that this research is regulated through the right to withdraw and mandatory re-consent despite the fact that these restrictions were designed for live subject research and are nonsensical when applied to archival research. (246) But what has been neglected thus far is the cost of such restrictions. (247)

   These costs cannot be understated, especially in light of the potential archival research holds. (248) Regulation is expensive monetarily, of course. (249) As Steven Beckwith, writing on behalf of the University of California system of schools, has recently argued, for "noninvasive, low or no risk data collection, data sharing and data reuse," the current regulatory structure leads to "major delays and higher costs in research, making some important research unfeasible." (250) But the costs go well beyond money. (251) Regulation such as the right to withdraw and mandatory re-consent can kill beneficial research by making it impossible or lowering its statistical power. (252) Ultimately, this result means that the viability of biobanks and tissue repositories, institutions which society depends upon for cures and hope regarding diseases such as cancer, is unduly threatened. (253)

   1. Direct Costs of the Right to Withdraw

      First, the right to withdraw threatens to lead to selection bias in archival research. (254) Selection bias is a major concern with any population-based study and occurs whenever the samples analyzed by a researcher are no longer a random representation of the population under study. (255) The existence of the right to withdraw means that, no matter how careful a researcher is in selecting a representative group of samples to study, archival research projects will always be at risk of selection bias because of the chance that some donors will withdraw their samples and, in the process, destroy the randomness. (256) Soren Holm illustrates how withdrawal can lead to this result:

      Withdrawal is a cumulative process, and insofar as new recruitment to the biobank is impossible (for in stance in time limited cohort biobanks), withdrawals will over time make the biobank smaller and smaller, and in cohort biobanks less and less representative of the original cohort of donors, because those who withdraw are very unlikely to be a random sample of the participants. (257) If this selection bias results, ongoing archival research can be rendered meaningless, as this bias distorts conclusions and under mines findings. (258)

      Second, withdrawal threatens the statistical power of archival research, which depends in large part upon the number of samples included in a study. (259) The fewer samples involved, the less confidence can be attributed to any result found by a study. (260) As stated earlier, archival research studies often depend on large population sizes to detect results. (261) And unfortunately, many biobanks face difficulty in securing archival material to begin with. (262) For example, the NCI established the Office of Biorepositories and Biospecimen Research in 2005 to address and resolve the "significant roadblock to cancer research" that the limited availability of archival material represents. (263) Couple the need for large population sizes with the already limited amount of material available, and there is little leeway for samples to be withdrawn without greatly reducing the statistical significance of any findings. (264)

      These two costs of the right to withdraw--selection bias and undermining of statistical power--are especially troubling for research studies that have already incurred heavy investments of time and money. (265) Such costs incurred storing and analyzing these samples before withdrawal cannot be recovered. (266) But even if research has not already incurred such heavy investments, withdrawal still results in waste. (267) Withdrawal "not only diminishes the scientific value of the bank, [but] also diminishes the value of the contribution of each of those participants who do not withdraw." (268)

      These costs are also troubling because of their permanence. (269) Because withdrawals typically result in the destruction of samples, there is no room for the donor to again change her mind after exercising her right to withdraw. (270) By removing her sample from one project, a donor has forever withdrawn her sample from contributing to future research studies, even the ones she would have no objection to. (271) This can have devastating results when a donor's reason for withdrawal is due to something like a malicious story about abuses at a biobank that is later proven to be fabricated. (272) When the donor learns of the fabrication, it is too late for her to take back her with drawal request. (273) No one benefits in such a scenario. (274)

   2. Direct Costs of Mandatory Re-Consent

      Similar to the right to withdraw, mandatory re-consent presents significant problems to archival research. (275) Joanna Forsberg has presented three obstacles that the need to get informed consent for each particular research study raises. (276) First, valuable resources are consumed securing consent rather than in beneficial research. (277) Often multiple letters have to be sent in order to receive a response and, sometimes researchers have to resort to phone calls and personal visits. (278) As illustrated above, researchers often cannot spare these types of extra expenses. (279)

      Second, Forsberg argues that mandatory re-consent, like with the right to withdraw, presents an enhanced risk of selection bias. (280) As her colleague Mats Hansson has pointed out, studies have shown that sending out forms asking for renewed consent are generally returned, with positive or negative responses, anywhere between 50%-90% of the time. (281) And most of the reason for this poor response rate is apathy and misconception, not any principled objection. (282) According to studies compiled by Korkeila et. al., common reasons for non-response have been wrong address, (283) forgetfulness/lack of time, (284) lack of interest in the topic, (285) lack of confidence, (286) and even present illness. (287) Indeed, a study concerning parents' non-return of consent forms regarding their children's participation in studies has found that the non-return of these forms was due to latent consent rather than deliberate refusal. (288)

      Such low response rates always present the hazard of selection bias, because the resultant sample is likely to be non-random. (289) For example, a 1998 prospective study on the psychosocial health of a randomly chosen sample of Finnish working-aged people resulted in only a 40% response rate to a questionnaire sent out. (290) An analysis of those not responding showed that compared to those who did respond there were a disproportionate number of men, senior citizens, lower educated persons, divorced or widowed persons, and disabled persons. (291) And while such factors as having a disproportionate number of men fail to respond are generally common across studies, sometimes responses can skew around factors related solely to the nature of the particular study. (292) For example, a study on airborne occupational exposure and respiratory disorders in Norway experienced selection bias because a disproportionate number of smokers failed to respond to the first letter, while a disproportionate number of those suffering from respiratory disorders did respond. (293)

      As discussed in regard to the right to withdraw, such selection bias can kill the worth of studies by decreasing their scientific importance. (294) For example, past studies finding a relationship between paternal occupations and birth defects have been criticized for having low statistical power as a result of selection bias and the consequent small sample sizes. (295) Sometimes researchers themselves have to retract their own prior scientific findings after more closely examining the possibility of selection bias. (296) For instance, researchers unexpectedly finding no link between Hodgkin lymphoma and higher social class were forced to admit that their findings were likely inaccurate as a result of selection bias in the control group. (297)

      The last argument Forsberg makes is that mandatory re-consent, in addition to consuming valuable resources and increasing the risk of selection bias, creates disincentives for initializing new studies. (298) Unsurprisingly, the logistical difficulties of obtaining consent can even lead to the abandonment of potentially valuable, ongoing research projects. (299) Some fields are especially hard hit. (300) For example, the endemic of low participation rates for sociometric research--the study of social relationships--devastates that field, (301) while the inability to presume consent has seriously harmed the viability of emergency neonatal research. (302) Taken together, the misallocation of expenses, the increased risk of selection bias, and the disincentives for new studies have the potential of devastating archival research. (303)

   3. Indirect Costs of the Right to Withdraw and Mandatory Re-Consent

      In addition to such direct costs of selection bias and unnecessary expenditures, society, which depends on these large-scale population studies for medical progress, is undoubtedly harmed indirectly by the right to withdraw and mandatory re-consent. (304) Some of the biggest advances in medical history, such as the link between smoking and lung cancer, were discovered or proven by archival research. (305) But because of the cost and quality concerns presented by the right to withdraw and mandatory re-consent, the discovery of similar advances in the future may be "too costly." (306) While the current system of regulation does not preclude such future health contributions from archival research, it undoubtedly means that such life-saving...