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Good deeds and Google
Editorial
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Stopping trials early for benefit: too good to be true
For the paper by Trotta et al see Annals of Oncology 2008; published online April 9. DOI:10.1093/annonc/mdn042 For the paper by Montori et al see JAMA 2005; 294: 2203–09. DOI:10.1001/jama.294.17.2203
When a randomised controlled trial (RCT) demonstrates dramatic superiority at interim analysis, stopping that trial early could save money and lives by hastening the availability of an effective intervention. In a study published on April 9 in Annals of Oncology, Francesco Trotta and colleagues examined the strength of data from trials for anticancer drugs that had been stopped early for benefit. Their findings question the robustness of shortterm data. Of the 25 trials, six had no data and safety monitoring board (DSMB) and five had enrolled less than 40% of the sample size. Even so, 11 were used to support licensing applications on the basis of what could have been exaggerated chance events. Controversy about the scientific credibility of RCTs stopped early for benefit is not new. In 2005, Victor Montori and colleagues published a systematic review of 143 such trials (55 of which had been published in the New England Journal of Medicine). Half the studies were halted after the first interim analysis, many driven by composite endpoints. Reporting was poor: only eight RCTs followed CONSORT guidelines. The median
risk ratio was 0·53 for the intervention after 66 events in 64% of the sample size during 13 months’ followup. Despite the fact that smaller data sets overestimate putative effect sizes, sensational positive results receive disproportionate attention and can bias practice, guidelines, and meta-analyses. The sense of urgency to stop a trial early could be misleading, since Trotta’s group found a 2-year delay between stopping and publication. To stop a trial early should therefore require proof beyond reasonable doubt that equipoise no longer exists. DSMBs must balance the decision to stop, which favours immediate stakeholders (participants, investigators, sponsors, manufacturers, patients’ advocates, and editors), with continuing the study to obtain more accurate estimates of not only effectiveness, but also of longer-term safety. In judging whether or not to stop a trial early for benefit, the plausibility of the findings and their clinical significance are as important as statistical boundaries. The same principles should guide the application of such findings to policy and practice. ■ The Lancet
Google/UNHCR
Good deeds and Google
For more on UNHCR and Google Earth Outreach see http://www. unhcr.org/googleearth
1310
Last week, internet giant Google and the UN High Commissioner for Refugees (UNHCR) launched an online site that enables users to get a bird’s eye view of displacement camps in Chad, Darfur, Iraq, and Colombia. Google designed Google Earth Outreach for organisations like UNHCR to raise public awareness about their work. UNHCR experts think that the site will eventually be able to help the agency and its partners to share geographic records of their efforts on the ground. This initiative is not Google’s first foray into not-for-profit work. Other recent projects include an online site that tracks progress towards the Millennium Development Goals and partnerships with the Rwandan Government and Kenyan universities to provide free communications applications, including email and word processing. In addition to these efforts, Google has a 4-year-old philanthropic arm—Google.org—which receives 1% of the company’s equity, 1% of its profits, plus employees’ time. In January this year, Google.org unveiled the strategy for its philanthropic work over
the next 5–10 years. It launched five core initiatives in three key areas: fighting climate change, economic development, and early warning systems for emerging threats such as pandemic influenza. As of January, 2008, Google.org has committed over US$75 million in grants and investments to further its philanthropic vision. The development of Google.org’s strategy was led by experienced public-health doctor Larry Brilliant, whose previous work includes a key role in WHO’s smallpox eradication programme. Brilliant was appointed executive director of Google.org in 2006. With the new strategy he has chosen to focus on initiatives in which the internet company has a comparative advantage— those that concentrate on information and technology. Although the fruits of this approach remain to be seen, it is likely to generate innovative and original tools to protect health and further development such as the company’s latest offering to highlight humanitarian crises. Google.org is a welcome addition to a growing and varied philanthropic landscape. ■ The Lancet www.thelancet.com Vol 371 April 19, 2008
Science Photo Library
Stopping trials early for benefit: too good to be true
For the paper by Trotta et al see Annals of Oncology 2008; published online April 9. DOI:10.1093/annonc/mdn042 For the paper by Montori et al see JAMA 2005; 294: 2203–09. DOI:10.1001/jama.294.17.2203
When a randomised controlled trial (RCT) demonstrates dramatic superiority at interim analysis, stopping that trial early could save money and lives by hastening the availability of an effective intervention. In a study published on April 9 in Annals of Oncology, Francesco Trotta and colleagues examined the strength of data from trials for anticancer drugs that had been stopped early for benefit. Their findings question the robustness of shortterm data. Of the 25 trials, six had no data and safety monitoring board (DSMB) and five had enrolled less than 40% of the sample size. Even so, 11 were used to support licensing applications on the basis of what could have been exaggerated chance events. Controversy about the scientific credibility of RCTs stopped early for benefit is not new. In 2005, Victor Montori and colleagues published a systematic review of 143 such trials (55 of which had been published in the New England Journal of Medicine). Half the studies were halted after the first interim analysis, many driven by composite endpoints. Reporting was poor: only eight RCTs followed CONSORT guidelines. The median
risk ratio was 0·53 for the intervention after 66 events in 64% of the sample size during 13 months’ followup. Despite the fact that smaller data sets overestimate putative effect sizes, sensational positive results receive disproportionate attention and can bias practice, guidelines, and meta-analyses. The sense of urgency to stop a trial early could be misleading, since Trotta’s group found a 2-year delay between stopping and publication. To stop a trial early should therefore require proof beyond reasonable doubt that equipoise no longer exists. DSMBs must balance the decision to stop, which favours immediate stakeholders (participants, investigators, sponsors, manufacturers, patients’ advocates, and editors), with continuing the study to obtain more accurate estimates of not only effectiveness, but also of longer-term safety. In judging whether or not to stop a trial early for benefit, the plausibility of the findings and their clinical significance are as important as statistical boundaries. The same principles should guide the application of such findings to policy and practice. ■ The Lancet
Google/UNHCR
Good deeds and Google
For more on UNHCR and Google Earth Outreach see http://www. unhcr.org/googleearth
1310
Last week, internet giant Google and the UN High Commissioner for Refugees (UNHCR) launched an online site that enables users to get a bird’s eye view of displacement camps in Chad, Darfur, Iraq, and Colombia. Google designed Google Earth Outreach for organisations like UNHCR to raise public awareness about their work. UNHCR experts think that the site will eventually be able to help the agency and its partners to share geographic records of their efforts on the ground. This initiative is not Google’s first foray into not-for-profit work. Other recent projects include an online site that tracks progress towards the Millennium Development Goals and partnerships with the Rwandan Government and Kenyan universities to provide free communications applications, including email and word processing. In addition to these efforts, Google has a 4-year-old philanthropic arm—Google.org—which receives 1% of the company’s equity, 1% of its profits, plus employees’ time. In January this year, Google.org unveiled the strategy for its philanthropic work over
the next 5–10 years. It launched five core initiatives in three key areas: fighting climate change, economic development, and early warning systems for emerging threats such as pandemic influenza. As of January, 2008, Google.org has committed over US$75 million in grants and investments to further its philanthropic vision. The development of Google.org’s strategy was led by experienced public-health doctor Larry Brilliant, whose previous work includes a key role in WHO’s smallpox eradication programme. Brilliant was appointed executive director of Google.org in 2006. With the new strategy he has chosen to focus on initiatives in which the internet company has a comparative advantage— those that concentrate on information and technology. Although the fruits of this approach remain to be seen, it is likely to generate innovative and original tools to protect health and further development such as the company’s latest offering to highlight humanitarian crises. Google.org is a welcome addition to a growing and varied philanthropic landscape. ■ The Lancet www.thelancet.com Vol 371 April 19, 2008