Angioplasty balloon, phot by denn via Flickr
As its title “Sex-Specific Reporting of Scientific Research” suggests, a focus of the IOM Workshop was whether medical journals could drive reform in this area by requiring that authors report sex-specific data. Wizemann writes that because “[r]esearchers are eager to have their papers published in high-profile journals[,]” “editorial policies implemented by those journals can be effective in modifying behavior.” But several participants in the IOM Workshop noted that studying population subgroups poses “methodologic and analytic” challenges. In many cases, Wizemann reports, “achieving statistical significance for subgroup analyses would require unattainable or unjustifiable numbers of participants.” Workshop participant Gregory Curfman, who is the Executive Editor of the New England Journal of Medicine, “cautioned against editorial policies that require trials to be designed to reach valid statistical conclusions for males and females separately[,]” because “[s]uch editorial policies would create a ’steep mountain to climb for investigators and for funding agencies[.]‘”
The participants in the Workshop seemed to be largely in agreement that journals could not, acting alone, re-shape “research culture to embrace consideration of sex differences as part of sound study design.” There are steps that journals could (and should, I think) take short of dictating study design, though, including requiring study authors to tabulate and make available raw sex-specific data to facilitate future studies that draw on data from multiple trials.
Government agencies and other funders have a role to play too. The NIH should more stringently enforce the statutory requirement that certain later-stage trials it funds be designed to evaluate sex-linked differences, and the FDA should take similar action with regard to trials funded by drug and device companies.
A study published last year by Sanket Dhruva, Lisa Bero, and Rita Redberg in the journal Circulation highlighted how little progress the FDA made on the device side over the last decade. In 1994, the FDA issued a directive requiring that every time it makes a decision on an application for approval to market a new device, it issue a Summary of Safety and Effectiveness Data (SSED) that includes, among other things, a “gender bias” statement addressing the following two questions: (1) Did the proportion of men and women in the clinical trial reflect the distribution of the disease? and (2) Were there any sex-linked differences in safety or effectiveness? Dhruva and colleagues reviewed all of the of the SSEDs for all of the cardiovascular premarket approval applications submitted and approved between 2000 to 2007 and found (1) that women were underrepresented in the underlying clinical trials and (2) that less than half (41%) of the SSEDs included the required “gender bias comment or analysis.” Nearly a third (28%) did not even report the percentages of men and women enrolled in the studies supporting the application. And, there was no improvement over time; “[t]here was no change in the presence of gender bias comments or analyses over the 8-year period” studied.
The FDA has been working for several years to address the problem and in December of 2011 it released a draft guidance in which it “strongly recommends” that device companies work closely with the agency to “investigate and report differences in study outcomes of treatment by sex.”
The Guidance provides clear direction for companies regarding (1) increasing the percentage of enrollees in device trials who are women, (2) designing studies to allow for the “consideration of sex and associated covariates” such as body size, (3) analyzing study data for sex-linked differences, and (4) “reporting sex-specific information in summaries and labeling for approved devices.” Whether these strong recommendations translate into strong and consistent agency action remains to be seen, but the Guidance is an excellent start. As Carolyn Clancy, the Director of the Agency for Healthcare Research and Quality, who participated in the IOM Workshop, emphasized, “[b]etter data on women would be better data for everyone,” allowing for more specific clinical practice guidelines and better-tailored care of individual patients.
Angioplasty balloon, phot by denn via Flickr
As its title “Sex-Specific Reporting of Scientific Research” suggests, a focus of the IOM Workshop was whether medical journals could drive reform in this area by requiring that authors report sex-specific data. Wizemann writes that because “[r]esearchers are eager to have their papers published in high-profile journals[,]” “editorial policies implemented by those journals can be effective in modifying behavior.” But several participants in the IOM Workshop noted that studying population subgroups poses “methodologic and analytic” challenges. In many cases, Wizemann reports, “achieving statistical significance for subgroup analyses would require unattainable or unjustifiable numbers of participants.” Workshop participant Gregory Curfman, who is the Executive Editor of the New England Journal of Medicine, “cautioned against editorial policies that require trials to be designed to reach valid statistical conclusions for males and females separately[,]” because “[s]uch editorial policies would create a ’steep mountain to climb for investigators and for funding agencies[.]‘”
The participants in the Workshop seemed to be largely in agreement that journals could not, acting alone, re-shape “research culture to embrace consideration of sex differences as part of sound study design.” There are steps that journals could (and should, I think) take short of dictating study design, though, including requiring study authors to tabulate and make available raw sex-specific data to facilitate future studies that draw on data from multiple trials.
Government agencies and other funders have a role to play too. The NIH should more stringently enforce the statutory requirement that certain later-stage trials it funds be designed to evaluate sex-linked differences, and the FDA should take similar action with regard to trials funded by drug and device companies.
A study published last year by Sanket Dhruva, Lisa Bero, and Rita Redberg in the journal Circulation highlighted how little progress the FDA made on the device side over the last decade. In 1994, the FDA issued a directive requiring that every time it makes a decision on an application for approval to market a new device, it issue a Summary of Safety and Effectiveness Data (SSED) that includes, among other things, a “gender bias” statement addressing the following two questions: (1) Did the proportion of men and women in the clinical trial reflect the distribution of the disease? and (2) Were there any sex-linked differences in safety or effectiveness? Dhruva and colleagues reviewed all of the of the SSEDs for all of the cardiovascular premarket approval applications submitted and approved between 2000 to 2007 and found (1) that women were underrepresented in the underlying clinical trials and (2) that less than half (41%) of the SSEDs included the required “gender bias comment or analysis.” Nearly a third (28%) did not even report the percentages of men and women enrolled in the studies supporting the application. And, there was no improvement over time; “[t]here was no change in the presence of gender bias comments or analyses over the 8-year period” studied.
The FDA has been working for several years to address the problem and in December of 2011 it released a draft guidance in which it “strongly recommends” that device companies work closely with the agency to “investigate and report differences in study outcomes of treatment by sex.”
The Guidance provides clear direction for companies regarding (1) increasing the percentage of enrollees in device trials who are women, (2) designing studies to allow for the “consideration of sex and associated covariates” such as body size, (3) analyzing study data for sex-linked differences, and (4) “reporting sex-specific information in summaries and labeling for approved devices.” Whether these strong recommendations translate into strong and consistent agency action remains to be seen, but the Guidance is an excellent start. As Carolyn Clancy, the Director of the Agency for Healthcare Research and Quality, who participated in the IOM Workshop, emphasized, “[b]etter data on women would be better data for everyone,” allowing for more specific clinical practice guidelines and better-tailored care of individual patients.