What Will It Take to Get IRB Reform?

Although many voices are joining together to call for reform of regulations governing institutional review board (IRB) oversight of research involving human subjects— and some of those voices even agree on how the IRB process should be reformed—progress in the United States toward such reforms is glacial. Unfortunately, the foot-dragging on reform may be costing the United States its leadership role in health research.

Current U.S. regulations governing protection of human subjects have their roots in the 1960s and especially the 1970s, when the National Research Act became law in 1974, spurred by the publicity surrounding the Tuskegee Syphilis Study. In that famous study of black males observed from 1932 to 1972, investigators denied penicillin to infected men. The National Research Act prompted the creation of the National Com- mission for the Protection of Human Subjects of Biomedical and Behavioral Research.1

Now, almost 40 years after enactment of that law, the U.S. health system is evolving faster than the rules to govern it. For example, how do we best regulate comparative effectiveness research (CER)? CER is a hybrid of both clinical trial research, which requires an IRB, and quality improvement processes, which are typically IRB exempt.

Electronic medical records also present a challenge. For example, the President’s Council of Advisors on Science and Technology recently released a report2 that on the one hand recommends personally determined data tagging and stres- ses the need for privacy safeguards, while on the other hand advocating the recommendation of the recent Institute of Medicine report3 to permit greater access to health data to facilitate research.

It is no wonder that the U.S. government provides incon- sistent recommendations. In addition to the Food and Drug Administration, 19 other federal agencies are involved in oversight for protection of study participants. There are more than 6,000 IRBs registered with the Department of Health and Human Services.

Inconsistent outcomes appear to be increasingly likely when the same protocol is presented to different local IRBs, as is common in a multicenter trial.4,5 One study of 88 pediatric practices found that local IRB review appears to be a barrier to participation in research, ‘‘may discourage the inclusion of minority and urban patients, and seems to result in little if any significant change’’ in the (minimal risk) protocols.6 Pogorzelska et al.7 are among the many calling for local IRB reform, including clarification of spe- cific purposes of local review (e.g., ensuring cultural ap- propriateness), assurances that IRB members are trained in regulatory requirements, as well as ethical principles of
research, and consideration of central review mechanisms. This latter is perhaps the most controversial, as national, independent IRBs have been reviewing federally funded research only since 1996.

Five concerns with using an independent IRB are: (a) a perception of increased risk to the institution; (b) possible conflicts of interest among the sponsor, site, investigator, IRB, and IRB member; (c) the importance of local knowledge; (d) logistics between the IRB and the site; and (e) the cost of administrative support. Coleman8 opines that careful evalu- ation of the following factors will lead to appropriate use of independent IRBs: ‘‘the IRB’s reputation and references; composition of the board committee(s) and qualifications of committee members; access to scientific experts; accreditation status; support staff quantity, qualifications, and training; results of regulatory inspections; approval stringency and typical letters; meeting frequency; operational metrics, such as review times; and operating procedures, such as internal auditing and error handling.’’

Regardless of whether a local or independent IRB is used, some say that IRBs concentrate on the wrong things and consequently do not do a good job of protecting the patient. A small    e-mail    survey    (N = 28)    of    principal    investigators9    re- vealed that respondent PIs felt that consent forms were in- comprehensible, that IRBs focused on minutiae, and that they were more concerned with protecting the institution than the subjects. Problem areas and solutions proposed by the In- fectious Diseases Society of America10 not referenced earlier in this editorial include:

  •  Health Insurance Portability and Accountability Act (HIPAA): Remove research from list of HIPAA-covered activities;
  •  Studies including children: Provide updated guidance for key terms, make national review outcomes available and streamline the process;
  • Office of Human Research Protection: Provide increased funding and a clear mandate to produce timely updates in guidance and review.

Another suggestion made by Kim et al.11 is to stop regu- lating minimal risk research, which represents 41% of all new protocols reviewed by U.S. medical center IRBs at a cost of about $300,000 per year for each review.
Many of the solutions suggested by our colleagues are regulatory, not requiring legislation but having the force of law when implemented. Therefore, we urge President Obama to make speedy IRB reform a priority of his administration.

1. Khin-Maung-Gyi F. Local and central IRBs: a single mission. Virtual Mentor 2009; 11:317–20.

2. Executive Office of the President, President’s Council of Advisors on Science and Technology. (2010) Report to the President—Realizing the full potential of health informa- tion technology to improve healthcare for Americans: the path forward. www.whitehouse.gov/sites/default/files/ microsites/ostp/pcast-health-it-report.pdf (accessed Mar. 29, 2011).

3. IOM (Institute of Medicine). (2009) Beyond the HIPAA privacy rule: enhancing privacy, improving health through research. Washington, DC: The National Academies Press.

4. Helfand BT, Mongiu AK, Roehrborn CG, et al., MIST Investigators. Variation in institutional review board re- sponses to a standard protocol for a multicenter random- ized, controlled surgical trial. Journal of Urology 2009; 181:2675–9.

5. Stark AR, Tyson JE, Hibberd PL. Variation among insti- tutional review board in evaluating the design of a multi- center randomized trial. Journal of Perinatology 2010; 30: 163–9.

6. Finch SA, Barkin SL, Wasserman RC, et al. Effects of local institutional review board review on participation in na- tional practice-based research network studies. Archives of Pediatrics & Adolescent Medicine 2009; 163:1130–4.

7. Pogorzelska M, Stone PW, Cohn EG, et al. Changes in the institutional review board submission process for multicenter

8. Coleman S. Alternative IRB review. Journal of Clinical Re- search Best Practices 2009; 5(4). http://firstclinical.com/ journal/2009/0904_Alternative.pdf (accessed Mar. 29, 2011).

9. Whitney SN, Alcser K, Schneider CE, et al. Principal inves- tigator views of the IRB system. International Journal of Medical Sciences 2008; 5:68–72.

10. Infectious Diseases Society of America. Grinding to a halt: the effects of the increasing regulatory burden on research and quality improvement efforts. Clinical & Infectious Dis- eases 2009; 49:328–35.

11. Kim S, Ubel P, De Vries R. Pruning the regulatory tree. Nature 2009; 457:534–5.


Brenda K. Wiederhold


What Are the True Costs of Regulation

What Are the True Costs of Regulation?


Many researchers and clinicians working in cybertherapy create their own businesses, which allow them to protect their intellectual property. In the United States, small businesses create the majority of jobs but bear proportionally more of the cost burden of implementing laws and regulations than do larger companies. This is true primarily because larger companies enjoy economies of scale. However, estimates of the true costs of regulation vary widely.

A new study* found that companies with fewer than 20 employees pay 42% more per employee than companies with between 20 and 499 employees, and 36% more than companies with 500 or more employees. For small businesses, the average cost per employee was $10,585 compared to $7,454 for medium-sized and $7,755 for large businesses.

According to the study, environmental regulations cost 364% more in small versus large companies, and tax compliance
is 206% higher. Occupational safety and health and homeland security are other top cost drivers.

The researchers calculated that some types of industry pay more than others. For example, small manufacturers (such as small manufacturers of medical devices) pay 110% more for compliance than medium-sized manufacturers and 125% more than large manufacturers. Small health-care firms (such as cybertherapy clinics) pay 45% more than medium firms and 28% more than large firms.

The authors say the total cost of regulation is $1.75 trillion, and note that businesses must close shop, reallocate activity, absorb the cost, or pass on the costs to customers. They estimate the per-household cost of federal regulation and taxes at $37,962.

The report notes, ‘‘If federal regulations place a differentially large cost on small business, this potentially causes inefficiencies in the structure of American enterprises and the relocation of production facilities to less regulated countries, and adversely affects the international competitiveness of domestically produced American products and services.’’

Some say that the above numbers are inflated and the study methodology is questionable, pointing to the annual report of the Office of Management and Budget (OMB) on the costs and benefits of regulation for a truer picture of the cost of regulation.

The OMB report notes that ‘‘The estimated annual benefits of major Federal regulations reviewed by OMB from October 1, 1999, to September 30, 2009, for which agencies estimated and monetized both benefits and costs, are in the aggregate between $128 billion and $616 billion, while the estimated annual costs are in the aggregate between $43 billion and $55 billion,’’ and that ‘‘Most rules have net benefits, but some rules have net costs.’’

Regardless of which of these estimates is closer to the true cost of regulation, the truth is that many regulatory costs are fixed: they are the same whether a company has 20 employees or 20,000. And the 89% of U.S. companies that have fewer than 20 employees produce a significant number of innovations. As President Obama has said, ‘‘Small businesses are the heart of the American economy.’’

In fall 2010, President Obama signed the Small Business Jobs Act, designed to help small businesses have easier access to credit and to provide more tax breaks. While a worthy effort, it does nothing to stem the tide of ever more regulation coming out of Washington.

Regulation per se is neither good nor bad. Rather, regulation in which the benefit outweighs the cost is good; regulation in which the cost outweighs the benefit is bad. Not all benefits can be quantified, which further complicates the picture.

It is time to start a serious dialog about the true cost of regulation, one that uses methodologically sound benefit–cost ratios as a starting point. I encourage readers to become involved in commenting on proposed regulations, so that only those regulations that pass the benefit–cost test are implemented. It is important to do so: the very future of innovation in health technology is at stake.

                                                                                                                                                                                                         Brenda K. Wiederhold