This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Efficacy and Safety Study of Tenofovir Disoproxil Fumarate (TDF) in Chinese Chronic Hepatitis B (CHB) Subjects With Advanced Fibrosis & Compensated Cirrhosis (NCT02224456), a na phase 4 study. The primary outcome is Incidence Rate of Newly Diagnosed Hepatocellular Carcinoma (HCC) at Week 240.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02224456 |
| Phase | Phase 4 |
| Condition | Hepatitis B, Chronic |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 197 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Chinese participants with chronic hepatitis B and advanced fibrosis or compensated cirrhosis were the target population. The primary endpoint population was the modified intent-to-treat population: recruited participants who received at least one dose of study medication. The registry record lists an enrollment of 197.
Intervention
The study evaluated tenofovir disoproxil fumarate (TDF), described as a 300 mg tablet taken once daily for 240 weeks. Participants receiving add-on rescue treatment could also take LAM, ETV or LdT at the listed daily doses, at the investigator’s decision.
Comparator
There was no concurrent control group. The study is registered as a single-group, non-randomized, open-label cohort, so it does not provide a like-for-like comparison between TDF and another assigned treatment.
Primary question
The primary question was the incidence rate of newly diagnosed hepatocellular carcinoma (HCC) at Week 240. The registry defines qualifying cases from Week 24 to Week 240 and reports the endpoint unit as events per person-year. A numerical incidence-rate result is not reported in the registry record.
The study was designed to examine long-term TDF treatment in Chinese participants with chronic hepatitis B and advanced liver disease. The registry also lists outcomes concerning disease progression, liver stiffness, HBV DNA, alanine aminotransferase normalization, and hepatitis B e antigen responses. Those outcomes provide additional descriptions of disease and treatment over time, but the record does not give their numerical results either.
3. Trial Design
The registry describes a prospective, multicenter cohort study and classifies it as Phase 4. Its registered design is single-group, with no random allocation and no masking. The study status is completed. The listed start date is 2015-03-25, and the primary completion date is 2020-12-04.
Participants received TDF 300 mg once daily for 240 weeks. The description allows add-on rescue treatment with LAM 100 mg, ETV 0.5 mg or LdT 600 mg per day, based on the investigator’s decision. Because rescue treatment could be added during follow-up, the study regimen was not necessarily identical for every participant throughout the study. The record does not report how many participants received each rescue treatment or when they received it.
The brief summary states that the study planned to enroll 240 subjects; the registered enrollment is 197. The registry record does not explain this difference. It also does not report a sample-size justification or the reasons for the planned enrollment target.
The absence of a concurrent comparator is important to interpretation. The study can describe event rates and other outcomes among participants followed under this treatment strategy, but it cannot by itself separate treatment effects from the natural course of disease, changes in care, or other differences over time. Open-label status means masking was not used; the registry does not describe additional procedures to reduce assessment bias.
The primary endpoint uses the modified intent-to-treat population, defined as recruited participants who received at least one dose of study medication. The registry does not give the number included in this population or explain how missing follow-up, withdrawals, or other departures from follow-up were handled.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: A total of 266 participants were screened, of which 197 entered the study.
Overall Study
| Stage | Tenofovir Disoproxil Fumarate 300 mg |
|---|---|
| STARTED | 197 |
| COMPLETED | 161 |
| NOT COMPLETED | 36 |
Reasons for not completing this period:
| Reason | Tenofovir Disoproxil Fumarate 300 mg |
|---|---|
| Lack of Efficacy | 1 |
| Lost to Follow-up | 15 |
| Withdrawal by Subject | 9 |
| Physician Decision | 3 |
| Death | 2 |
| Pregnancy | 4 |
| Protocol Violation | 1 |
| Treatment Interruptions of ≥28 days | 1 |
Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-treat (mITT) Population consisted of all recruited participants who received at least one dose of study medication.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Baseline characteristics is presented for modified Intent-to-treat (mITT) Population which consisted of all participants who received at least one dose of study medication. 2 participants did not receive TDF treatment thus excluded from mITT Population
| Characteristic | Unit | Tenofovir Disoproxil Fumarate 300 mg |
|---|---|---|
| Participants analysed | 195 | |
| Age, Continuous | Years | 42.3 (SD 9.80) |
| Sex: Female, Male: Female | Participants | 47 |
| Sex: Female, Male: Male | Participants | 148 |
| Race/Ethnicity, Customized: Asian | Participants | 195 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence Rate of Newly Diagnosed Hepatocellular Carcinoma (HCC) at Week 240, measured over Week 240.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Events per person-year |
| Endpoint classification | Event-Rate Endpoint |
The primary endpoint is the incidence rate of newly diagnosed hepatocellular carcinoma (HCC) at Week 240, expressed as events per person-year. The registry defines qualifying HCC cases as those arising from Week 24 to Week 240. Participants had to be without HCC before Week 24, and a case had to meet the specified diagnostic criteria: histological diagnosis, or qualifying imaging findings for nodules >2 cm using either listed imaging approach, or for nodules >1 cm using both listed approaches.
An incidence rate relates the number of qualifying events to the amount of time participants contribute under observation. In general, this can be useful when follow-up time differs across participants, because person-time accounts for the duration each participant is observed rather than treating every participant as having an identical observation period. It is a rate, not simply the percentage of participants who experience the event.
HCC is the study’s specified primary clinical event. The registry record does not report the event count, accumulated person-time, incidence-rate estimate, or an uncertainty interval. Therefore, the endpoint definition and measurement unit can be described, but the observed rate and its precision cannot be assessed from the registered results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies HCC incidence by Week 240 as the primary outcome, but does not report a numerical incidence rate or the information needed to reconstruct one. In particular, the record does not state the number of qualifying HCC events, the total person-time, or an uncertainty interval. Without those elements, the magnitude and precision of the primary result cannot be evaluated. The endpoint definition alone is not an outcome result.
The design also limits what any observed rate could establish. This was a single-group, open-label cohort without random allocation or a concurrent control. An event rate among participants receiving the study treatment strategy would describe what occurred in that cohort; it would not by itself show what would have occurred under another treatment or without treatment. Differences in participant characteristics, disease course, care, and follow-up could contribute to outcomes. The registry does not report an adjustment strategy that would address such comparisons.
The term “incidence rate” should not be read as a proportion. Its denominator is person-time, so interpretation depends on both the number of events and the observation time contributing to the rate. The posted record supplies neither an estimate nor its constituent count and exposure time. Consequently, there is no basis in the registry record for characterizing the rate as high, low, increased, or decreased.
The registry lists secondary outcomes at specified follow-up weeks, including HCC, disease progression, liver stiffness, HBV DNA, ALT normalization, and HBeAg outcomes. It does not provide their observed numerical results in the record. The presence of these outcome definitions should not be mistaken for evidence about their results.
Safety information is recorded separately. The adverse-event summary lists 34 participants affected by serious adverse events among 195 at risk, 129 affected by other adverse events among 195 at risk, and 2 deaths. These are descriptive counts in the registry’s treatment group, not evidence that the treatment caused the events. The record does not provide a comparison group or the detail needed to attribute individual events to treatment.
Overall, the posted record documents a completed cohort study and defines its primary outcome and population. It does not provide the primary endpoint estimate, its precision, or numerical results for the listed secondary outcomes. Statistical interpretation must therefore remain focused on the study design, outcome definitions, and reported safety counts rather than on unreported efficacy results.
9. Statistical Methods Explained
The registry classifies the primary endpoint as a rate, with the unit events per person-year. That distinction matters: an event rate uses accumulated observation time as its denominator, whereas a risk or percentage generally describes the proportion of people experiencing an event over a specified period. These measures answer related but different questions and should not be substituted for one another.
What does person-time contribute?
In general, person-time adds each participant’s time under observation until the relevant endpoint or the end of follow-up. A participant observed for longer contributes more exposure time than a participant observed for less time. This can be useful when follow-up duration varies. To interpret a rate, readers need both the event count and the total person-time, as well as an estimate of uncertainty. Those numerical details are not reported in the registry record for the primary endpoint.
The endpoint timeframe is Week 240, while qualifying HCC cases are defined from Week 24 to Week 240. The definition also specifies diagnostic routes for identifying cases: histology, or imaging findings that meet the listed criteria for nodules >2 cm or >1 cm. These criteria make the event definition more explicit, but do not reveal how many cases met it. The registry record does not state the endpoint adjudication procedures or report whether any cases were disputed.
How should a confidence interval be understood?
In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the statistical method. A narrower interval indicates greater statistical precision than a wider interval, but does not correct weaknesses in design or measurement. No confidence interval for the primary incidence rate is reported in the registry record, so its statistical precision cannot be described.
For a rate, uncertainty depends on the event information and exposure time, among other assumptions. In general, a small amount of event information can leave a rate estimate imprecise. If events occur more variably than a simple model assumes, over-dispersion can make conventional uncertainty estimates too small; methods that account for extra variability may then be appropriate. This is a general statistical consideration, not a statement about the distribution of events in this study. The registry does not report the fitted model, dispersion assumptions, or an analysis plan for the rate.
What does the single-group design allow?
In general, a single-group cohort can describe outcomes observed in participants who receive a specified care strategy. Without a concurrent comparison group, it cannot directly estimate a between-group treatment effect. Random allocation, when used, can help balance measured and unmeasured characteristics between treatment groups; this study is not registered as randomized. Its open-label status also means that masking was not used. The registry does not report a causal analysis intended to compensate for the absence of a comparator.
Participants could receive add-on rescue treatment at the investigator’s decision. In general, changes in treatment during follow-up can complicate interpretation of outcomes attributed to a treatment strategy. The registered description establishes that rescue treatment was permitted but does not report its use, timing, or how it was incorporated into endpoint analyses.
How should planning calculations be read?
In general, sample-size calculations describe a design under stated assumptions; they are not observed results and are not “observed power.” The registry record says its planning illustrations use a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation, with the target effect expressed as a stated fraction of an observed effect. For time-to-event illustrations, the stated convention is a total number of events; for other illustrations, it is participants per arm. These are planning assumptions, not evidence that this trial had two randomized arms.
The registered trial itself is single-group, and the record does not report a sample-size justification for its own design. A planning calculation based on a hypothetical comparison cannot create a comparator in the actual study. Nor can a planning illustration establish the precision of the unreported primary rate. No numerical result from such an illustration is described in the registry record.
What analysis information is missing?
The registry record does not report the statistical model for the primary endpoint, how person-time was accumulated, how censoring or incomplete follow-up was handled, or whether any adjusted analysis was performed. It does not report a confidence interval, a p-value, or a numerical incidence-rate estimate. Without these details, readers cannot independently assess model assumptions or reproduce the primary analysis from the registry entry.
The endpoint population is defined as recruited participants who received at least one dose of study medication. In general, a clearly defined analysis population helps readers understand who contributes to an estimate. Here, the record does not state the number in that population or the rules for excluding participants, handling missing measurements, or analyzing participants who stopped treatment. Those omissions constrain reproducibility and interpretation.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists numerous secondary outcomes, including HCC and disease progression at several follow-up weeks, changes in liver stiffness and HBV DNA, ALT normalization among participants with abnormal ALT at baseline, and HBeAg responses among HBeAg-positive participants. It also lists 24 outcome measures. Having several outcomes or repeated assessments creates multiple opportunities for statistical findings, so a prespecified strategy for interpreting multiple tests can matter.
The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or an analysis plan for deciding which results would be treated as confirmatory. It also does not report whether interim analyses were planned or conducted. Those details are not reported in the registry record, and should not be inferred from the outcome list.
The record defines the primary endpoint population as recruited participants who received at least one dose of study medication. It does not provide the population size for that analysis, the number with evaluable endpoint follow-up, or the handling of missing data. It also does not explain how loss to follow-up, withdrawal, or incomplete outcome information affected each analysis.
These omissions matter because outcome estimates can depend on who is included and how incomplete follow-up is treated. They also prevent readers from checking whether the reported population matches the intended analysis population. Since numerical primary and secondary results are not reported in the registry record, the effect of missing data or multiplicity on any result cannot be assessed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Tenofovir Disoproxil Fumarate 300 mg | 34 | 195 | 17.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Tenofovir Disoproxil Fumarate 300 mg | 2 of 195 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tenofovir Disoproxil Fumarate 300 mg | 129 of 195 |
Most frequent serious adverse event terms
| Event term | Organ system | Tenofovir Disoproxil Fumarate 300 mg |
|---|---|---|
| Hepatocellular carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 13 of 195 |
| Cholelithiasis | Hepatobiliary disorders | 2 of 195 |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 195 |
| Ovarian germ cell teratoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 195 |
| Foot fracture | Injury, poisoning and procedural complications | 1 of 195 |
| Lower limb fracture | Injury, poisoning and procedural complications | 1 of 195 |
| Post procedural bile leak | Injury, poisoning and procedural complications | 1 of 195 |
| Radius fracture | Injury, poisoning and procedural complications | 1 of 195 |
| Spinal compression fracture | Injury, poisoning and procedural complications | 1 of 195 |
| Tibia fracture | Injury, poisoning and procedural complications | 1 of 195 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tenofovir Disoproxil Fumarate 300 mg |
|---|---|---|
| Upper respiratory tract infection | Infections and infestations | 36 of 195 |
| Hypophosphataemia | Metabolism and nutrition disorders | 15 of 195 |
| Urinary tract infection | Infections and infestations | 11 of 195 |
| Blood creatine phosphokinase increased | Investigations | 9 of 195 |
| Anaemia | Blood and lymphatic system disorders | 9 of 195 |
| Hypocalcaemia | Metabolism and nutrition disorders | 7 of 195 |
| Ascites | Gastrointestinal disorders | 6 of 195 |
| Toothache | Gastrointestinal disorders | 5 of 195 |
| Cholelithiasis | Hepatobiliary disorders | 5 of 195 |
| Hypertension | Vascular disorders | 5 of 195 |
Serious events with the highest arm-level rate: hepatocellular carcinoma (6.7%), cholelithiasis (1.0%), malignant melanoma (0.5%), ovarian germ cell teratoma (0.5%), foot fracture (0.5%).
The adverse-event summary lists 34 participants affected by serious adverse events among 195 at risk, and 129 participants affected by other adverse events among 195 at risk. It also lists 2 deaths. These are counts in the TDF 300 mg group as recorded; the summary does not establish that the treatment caused any event.
The registry lists these serious-event terms and percentages: hepatocellular carcinoma, 6.7%; cholelithiasis, 1.0%; malignant melanoma, 0.5%; ovarian germ cell teratoma, 0.5%; foot fracture, 0.5%; and lower limb fracture, 0.5%. These listed percentages should be read as registry-reported values. The record does not provide the event-level detail or the basis needed to independently interpret their timing, overlap, or relationship to treatment.
In general, adverse-event summaries describe events observed during a study; they do not by themselves distinguish events caused by treatment from events due to underlying illness or other causes. A comparison group can help contextualize event frequency, but this study has no concurrent control. The registry record also does not provide a detailed narrative for the deaths or a causal assessment for each serious event. The counts therefore support a descriptive reading of what was recorded, not a comparative or causal conclusion.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a prospective, multicenter, open-label, single-group study of TDF in Chinese participants with chronic hepatitis B and advanced liver disease was completed. It defines newly diagnosed HCC incidence by Week 240 as the primary endpoint and specifies the diagnostic criteria and analysis population. The record also reports safety counts and lists secondary outcomes.
It does not report the numerical primary endpoint result. There is no stated HCC event count, person-time total, incidence-rate estimate, or confidence interval. As a result, readers cannot determine the observed rate or its precision from the registry record. The defined endpoint is not itself proof of a particular outcome.
The study has no randomized or concurrent control group. Any descriptive outcome among its participants cannot, by itself, determine what would have happened under a different treatment strategy. This is especially relevant in a cohort where add-on rescue treatment was permitted at investigator discretion. The registered design and outcome definitions do not support a direct estimate of comparative treatment effect.
The record also does not state numerical results for the listed secondary outcomes. Consequently, the registry entry does not establish how HCC, disease progression, liver stiffness, HBV DNA, ALT, or HBeAg outcomes changed over follow-up. The absence of posted results in the record should not be interpreted as evidence that an outcome did or did not occur.
The safety summary gives descriptive counts: 34 participants affected by serious adverse events among 195 at risk, 129 affected by other adverse events among 195 at risk, and 2 deaths. Without a comparator and detailed causal assessments, those figures do not show that TDF caused the events. They should be understood as the events recorded in the study group.
In short, the registry supports an account of the study’s design, intended outcomes, and reported safety counts. It does not provide enough numerical efficacy information to quantify the primary endpoint or assess its precision, and it does not support a causal comparison with another treatment.
13. Why This Trial Matters Statistically
This study is statistically notable for the question it set out to address: a long-term HCC incidence rate in Chinese participants with chronic hepatitis B and advanced liver disease. The endpoint is expressed per person-year and includes explicit diagnostic criteria. These features clarify what event the study intended to count and what exposure-time framework was planned for its rate.
The design also illustrates the distinction between describing outcomes and estimating comparative effects. A prospective cohort can collect outcomes over time in a defined population, but a single-group design does not create a concurrent counterfactual. Without a randomized or other suitable comparator, an observed event rate cannot alone establish how outcomes would differ under another treatment strategy.
The registry includes follow-up outcomes spanning HCC, disease progression, liver stiffness, viral measures, liver enzyme normalization, and antigen responses. Such a breadth of outcomes makes clear why analysis plans for repeated measurements, missing data, and multiplicity are important. The registry record does not report those plans or the numerical results for these outcomes, so readers cannot assess whether findings were consistent across measures or how uncertainty was handled.
The record also distinguishes the planned enrollment target of 240 from the registered enrollment of 197, without explaining the difference. That makes transparent reporting of recruitment, analysis populations, follow-up, and precision especially relevant to readers evaluating the study’s evidence. Yet the primary incidence-rate estimate and its uncertainty are not reported in the registry record.
The statistical importance of this record therefore lies in the relationship between its clinically specific outcome, its single-group cohort design, and the limited numerical results available. Clear definitions are valuable, but they cannot substitute for event counts, person-time, estimates, and uncertainty measures when assessing an incidence rate.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record leaves the primary result unavailable for quantitative interpretation: it does not report the number of qualifying HCC cases, the accumulated person-time, an incidence-rate estimate, or an uncertainty interval. It also does not report numerical results for the listed secondary outcomes. This prevents assessment of the magnitude and precision of the study’s outcomes.
The study is registered as a single-group, non-randomized, open-label cohort, so it lacks a concurrent like-for-like control comparison. The record does not describe a causal adjustment strategy. Participants could receive add-on rescue therapy at the investigator’s decision, but the frequency, timing, and analysis of rescue treatment are not reported.
The planned enrollment in the brief summary is 240, while registered enrollment is 197. The record does not explain the difference or provide a sample-size justification for the study’s own design. It also does not report the size of the modified intent-to-treat population, the extent of follow-up, or the handling of missing data, withdrawals, and incomplete endpoint assessments.
Methods needed to assess reproducibility are not reported, including the primary statistical model, construction of person-time, handling of censoring, and any model assumptions or adjustments. Multiplicity procedures, interim analyses, and an analysis hierarchy are also not reported in the registry record. These gaps limit evaluation of both the analysis and the broader set of planned outcomes.
Finally, the safety summary is descriptive and lacks a concurrent comparator and detailed event-level information. The listed counts and serious-event terms should not be interpreted as causal effects. The record does not report timing or causal assessment for each event, or a detailed account of the deaths.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety Study of Tenofovir Disoproxil Fumarate (TDF) in Chinese Chronic Hepatitis B (CHB) Subjects With Advanced Fibrosis & Compensated Cirrhosis — NCT02224456.
- Registry record last updated 2022-02-14; status last verified 2021-11.
- Results first posted 2022-02-14.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The record describes a completed, Phase 4, prospective multicenter cohort study of TDF in Chinese participants with chronic hepatitis B and advanced fibrosis or compensated cirrhosis. The registered design is single-group, open-label, and non-randomized. The listed enrollment is 197; the brief summary states a planned enrollment of 240. The study start date is 2015-03-25, and the primary completion date is 2020-12-04.
The primary endpoint is newly diagnosed HCC incidence at Week 240, defined as events per person-year, among recruited participants who received at least one dose of study medication. TDF was described as 300 mg once daily for 240 weeks, with add-on rescue treatment permitted at investigator discretion.
The registry reports safety counts and lists secondary outcome definitions, but does not report a numerical primary incidence-rate result, its precision, or numerical results for the secondary outcomes. The design does not include a concurrent comparator.