Trial Population

Table 1. Table 1. Characteristics of Clinical Trials That Were Completed or Terminated before September 2012.

Of the 13,327 HLACTs that we reviewed during the study period, 1790 (13.4%) reported results within 12 months after trial completion, and 5110 (38.3%) reported results at any time during the 5-year study period (Table 1, and Table S2 in the Supplementary Appendix). In contrast, among the 25,646 non-HLACTs, only 1287 (5.0%) reported results within 12 months, and 2473 (9.6%) reported results at any time during the 5-year study period (Table S3 in the Supplementary Appendix).

In our study cohort, the primary purpose was identified as treatment by 84.8% of the trials, prevention by 7.7%, and “other” (which included diagnostic, screening, supportive care, health services research, and basic science) by 7.5%. Trials were categorized according to their interventions, with drugs studied in 77.4% of the trials, devices in 11.9%, biologics in 8.9%, and “other” (including radiation and genetics) in 1.9%. The largest funding source was industry (65.6%); the National Institutes of Health (NIH) funded 14.2% of trials, and other government or academic institutions funded the remaining 20.2% (Table 1). Components of basic summary results are listed in Table S4 in the Supplementary Appendix.

Rates of Reporting

At 12 months, results had been reported for 17.0% of trials that were funded by industry, 8.1% of trials funded by the NIH, and 5.7% of trials funded by other government or academic institutions. At 5 years, results had been reported by 41.5% of trials funded by industry, 38.9% of those funded by the NIH, and 27.7% of those funded by other government or academic institutions. Additional details of summary results reporting are provided in Tables S3 through S6 in the Supplementary Appendix.

Table 2. Table 2. Reporting of Results to ClinicalTrials.gov.

By September 27, 2013, a total of 2100 of 13,327 HLACTs (15.8%) had submitted a certification or extension request to delay reporting to ClinicalTrials.gov. Of these HLACTs, 482 (23.0%) had reported results throughout the 5-year study period. At 12 months, 1790 of 13,314 trials (13.4%) that were evaluated had reported results and 818 (6.1%) had not reported results but had a legally acceptable delay because of a certification or an exemption request (Table 2). Phase 2 and phase 3 trials were more likely to have certification or exemption requests than were trials in other phases.

Time to Results Reporting

For trials with results, the median time to reporting for HLACTs was 17 months (interquartile range, 13 to 29) (Table 2). For the primary analysis, the median time to reporting was 16 months (interquartile range, 13 to 26) for industry-funded trials, 23 months (interquartile range, 14 to 36) for NIH-funded trials, and 21 months (interquartile range, 14 to 30) for other government or academic institutions (Table 2). After the exclusion of trials with certification or extension requests at any time in the secondary analysis, the median time to reporting decreased from 16 to 14 months for industry-funded trials but remained the same for NIH-funded trials and those funded by other government or academic institutions (Table 2).

Reporting over Time

Figure 2. Figure 2. Cumulative Percentage of Clinical Trials That Reported Results to ClinicalTrials.gov, According to the Time after the Primary Completion Date. NIH denotes National Institutes of Health.

Kaplan–Meier curves showing reporting of trial results during the 5-year study period according to funding source are provided in Figure 2. Industry-funded trials significantly led reporting for several years, but by 5 years, reporting rates of NIH-funded trials equaled those of industry-funded trials. Trials that were funded by other government or academic institutions had consistently lower rates of reporting over 5 years than did those funded by other sources (Fig. S1, S2, and S3 in the Supplementary Appendix).

Multivariable Factors Associated with Results Reporting

Reporting within 12 Months

Table 3. Table 3. Likelihood That Results of Clinical Trials Were Reported by 12 Months or 5 Years after the Primary Completion Date, According to Trial Characteristics.

The factors that were most strongly associated with reporting by 12 months were funding source, trial phase, and FDA oversight (P<0.001 for all comparisons) (Table 3, and Table S7 in the Supplementary Appendix). As compared with NIH-funded trials, industry-funded trials were more likely to report results in a timely fashion (adjusted odds ratio, 1.62; 95% confidence interval [CI], 1.34 to 1.97), whereas trials that were funded primarily by other government or academic institutions were less likely to report on time (adjusted odds ratio, 0.58; 95% CI, 0.45 to 0.75). As compared with phase 4 trials, earlier-phase trials were significantly less likely to report on time, with an adjusted odds ratio of 0.28 (95% CI, 0.21 to 0.38) for phase 1–2 combination trials, 0.33 (95% CI, 0.27 to 0.39) for phase 2 trials, 0.22 (95% CI, 0.14 to 0.36) for phase 2–3 combination trials, 0.60 (95% CI, 0.50 to 0.71) for phase 3 trials, and 0.56 (95% CI, 0.45 to 0.70) for trials in which the phase was not applicable (e.g., trials of devices). Trials without FDA oversight were less likely to report on time than those with FDA oversight (adjusted odds ratio, 0.61; 95% CI, 0.52 to 0.71). Sensitivity analyses revealed similar associations (Tables S8 and S9 in the Supplementary Appendix).

Reporting within 5 Years

Multivariable factors that were most strongly associated with results reporting during the 5-year study period included trial phase and funding source (P<0.001 for both comparisons) (Table 3, and Table S7 in the Supplementary Appendix). As compared with phase 4 trials, a stepwise decrease in reporting for phases was observed, with an adjusted hazard ratio of 0.46 (95% CI, 0.40 to 0.54) for phase 1–2 combination trials, 0.54 (95% CI, 0.49 to 0.59) for phase 2 trials, 0.54 (95% CI, 0.44 to 0.66) for phase 2–3 combination trials, and 0.80 (95% CI, 0.72 to 0.88) for phase 3 trials.

Industry-funded and NIH-funded trials were nearly equally likely to report results (adjusted hazard ratio, 0.97; 95% CI, 0.89 to 1.07) within 5 years, whereas trials that were funded by other government or academic institutions were less likely to report results than were NIH-funded trials (adjusted hazard ratio, 0.62; 95% CI, 0.56 to 0.70) (Table 3). After the exclusion of trials with certification or extension requests, a sensitivity analysis showed that industry-funded trials were more likely to report results within 5 years than were NIH-funded trials (Table S10 in the Supplementary Appendix). However, other sensitivity analyses that used a time-dependent covariate to account for whether reporting requirements were in effect did not change the primary finding that reporting rates over 5 years were similar for industry-funded and NIH-funded studies and were substantially lower for those funded by other government or academic institutions (Tables S11 through S14 in the Supplementary Appendix).

Findings from Sample Review

We manually reviewed a sample of 205 HLACTs to determine requirements for reporting (Tables S15A and S15B in the Supplementary Appendix). By reviewing approval dates and labeling information, we determined that 44 to 45% of industry-funded HLACTs in this sample were not required to report results, as compared with 6% of NIH-funded studies and 9% of those funded by other government or academic institutions. On the basis of this review, we estimated that during the 5-year period, approximately 79 to 80% of industry-funded trials reported summary results or had a legally acceptable reason for delay. In contrast, only 49 to 50% of NIH-funded trials and 42 to 45% of those funded by other government or academic institutions reported results or had legally acceptable reasons for delay.