Operational Integrity in Clinical Research
Opportunities for improving justice in research
Ethics review frameworks (Belmont, Declaration of Helsinki) demand a favorable risk–benefit ratio. But no national or international standard requires REBs to assess whether a study is operationally doable before participants are enrolled. Resultingly participants bear risks for studies that are predictably doomed to fail. Analysis of top 50,000 projects on ClinicalTrials.gov showed 68% projects completion, others facing termination, suspension, withdrawal, or unknown status. We assessed time of progress reporting after primary completion date as a possible indicator of increased project time, where sum of last update after primary completion date for all these trials was: 19 million days, and per project average reporting delay: 152 days / year. Reasons of termination stated in many projects included slow patient recruitment, where the project no more seems operationally viable.
Our Question is:
Should initial ethics review include a formal check on whether a study can actually be done?
It sounds simple. Yet no national or international research ethics framework requires REBs to systematically assess operational feasibility – things like recruitment access, team capacity, realistic timelines, or site approvals. Currently, it is left to individual REBs to include such review. When included, traditionally it is done with most basic questions on feasibility, missing the details of efficiency, and completed by ethics and scientific experts – without involving operations (project management or HR) experts.
This is not an administrative oversight. It is an ethical gap.
If a study cannot be completed as designed, participants bear risks for no potential benefit. That violates beneficence and makes informed consent an illusion.
“Feasibility and implementation capacity directly influence whether projected benefits can materialize – and therefore whether risks can be ethically justified.”
Operational Failures Are the Norm Globally, Not the Exception
| Finding | Source |
| 80% of clinical trials are delayed by at least one month | 2025 |
| ~30% of patients drop out; replacement costs ~3× initial recruitment | 2025 |
| Up to 80% of studies are underpowered due to flawed assumptions | 2024 |
| Accrual failure leads to underpowered studies in >30% of cases | 2024 |
These are not just financial problems – they are ethical failures.
An Overview of Canadian Research Landscape
Among the top 50,000 clinical trials listed on ClinicalTrials.gov, only 68% have reached completion. The remaining 32% have either been terminated, suspended, or unknown status/ withdrawn. Trials funded by the industry tend to have higher completion rates, although they also experience greater delays in reporting. The rates of completion and the associated delays vary significantly across different countries and funding sources, highlighting the impact of oversight and accountability mechanisms on the successful completion of these projects. Click on Canada in sites location chart, to visualize its data, comparing with other countries.
Above is a brief analysis in Power BI Dashboard (detailed dashboard is available on request, containing info of sponsors, sites, enrollment rates, funder type & diseases having different project outcomes & times of reporting).
Addressing Operational Challenges
Exploring Role of IRBs:
At BMY Health (Canada, Pakistan), we faced several operational challenges that led to delays/ non-completion of projects. Unfortunately, we were unable to find adequate guidance from any REB standards or related documents nationally & internationally to ensure oversight of operational integrity. This led us to devise our own operational review framework, using insights from our failing projects, now embedded in our IRB. An initial pilot testing of this IRB model showed a 33% reduction in negative project outcomes. We are currently gathering more data to further evaluate its impact & refine our model.
Operational aspects included in framework:
- Recruitment access (5Ws, & with patient engagement)
- Data collection tools efficiency
- Site approvals in place
- Team capacity & alignment
- Team retention & stakes in the project
- Defined schedules & accountability structure (often weak in non-funded individual/ academic research)
- Workflow efficiency
- Context adaptation (aligned with organization strengths & limitations)
- Contingency plans
Points assessed for 2 aspects of operations: 1. Feasibility 2. Efficiency.
Expertise for assessment: Project manager/ HR
The model was also presented in Canadian Bioethics Conference, May 2026. Abstract (page 28)
Role of Networks:
At BMY Health, we have strengthened our support systems for researchers by establishing collaborations with clinics and institutions to improve patient recruitment efforts. Institutions can further enhance their partnerships with recruitment networks, other sites, and countries that have a greater availability of patients, especially in areas with a high burden of disease. Although this may require expanding capacity and providing training on institutional standards and SOPs at remote sites, the investment fosters diversity and builds lasting connections, while also advancing Canada's global footprint & equity in research.
Role of Technology:
At BMY Health, we experienced significant improvements by integrating more technology into our data collection processes. Organizations can further enhance their recruitment strategies by leveraging advancements in technology, such as digital tools, artificial intelligence, and automation. Notably, this doesn't always necessitate substantial financial investments, as there are many affordable and no-code options available today.
Policy Recommendations
| Stakeholder | Recommendation | Cost | Opportunity |
| IRBs | Create a separate, low‑cost operational review. | Adding OR step can increase initial time of approval but | Can reduce IRB regulatory burden with failing & non-compliant projects, and enhances participant protection & ethical value of project. |
| Regulators & Policy Makers | Develop & enforce national standards for IRBs, explicitly require operational feasibility checks, especially for high‑risk studies. This is in line with TCPS2 proportionate review requirement. Enforce results reporting in public registries, including reasons for failure (sample reduction, non‑completion, delays). | Can face resistance, but support with more funding for building systems, expanding Canadian collaborations internationally for patients recruitment, and supporting institutions with technology for recruitment can earn more cooperation. | Can save Canadians from unnecessary harms through operationally weak studies, and build public trust. |
| Sponsors | Mandate operational review from project managers or institutional HR before funding sites for high‑risk projects. Estimated cost of operational review can be <$1,000 per project – which is far lesser than the costs of failing projects. However achieving operational integrity will require developing conducive systems for the team such as enough funding & stakes. | Estimated cost of operational review can be <$1,000 per project. Achieving operational integrity will however require developing conducive systems for the team such as enough funding & stakes | The investment on operational integrity is still expected to be lesser than the costs of failing projects. Studies have shown that delay in clinical trial by a month leads to potential losses of ~ $600,000 (or as high as $8 million)/ day. The cost of drop out is ~19,533 or higher per new patient recruitment after 1 drop out, compared to $6,533/ patient recruited in start of study. (1) Increasing initial investment offers greater predictability, more favorable for project, and protective of sponsor repute. |
| Sites/ Institutions | Expand capacity for recruitment through collaborations, patient engagement and co‑production models in research. Build technology to support researchers with efficient data collection tools such as automations. Retain well aligned teams, & support through the right environment. Support sponsors through transparency on site information helping them make informed choices, predicting outcomes. | Investment on building systems required | Return on investment through more opportunities for research & developments, building institutions legacy in science |
IRB Applicants | Detailed planning for project, including schedules details, accountability structure, back-up plans & workflows efficiency. | Time/ cost for project planning & details. | Investment of good operational early on is still expected to be lesser than the costs of failing projects, & protective of PIs repute/ academic career. This step before final approval also ensures that any major changes by IRB get screened by operational team for execution possibility. |
Ethics/ Public health/ Clinical Researchers | More studies on operational challenges and operational review frameworks. | Time, expertise | Contribution in bioethics field |
Why This Matters
Delays in projects are costly, wasting money & time of sponsors, researchers & participants.
Insufficient data leads to underpowered studies, or termination, compromising the risk benefit balance in research, making informed consent an illusion, and increasing mistrust.
Policy Gap in Canada
No national standards explicitly include & formally mandate operational review before start of project.
What Needs to Change
Add operational feasibility & efficiency check with IRB review – or as a mandatory parallel step before ethics approval.
Operational feasibility is an ethical imperative - not a bureaucratic detail.
We Need to Stop Wasting Participants' Time on Studies that cannot Succeed!
Some references:
- https://mdgroup.com/blog/the-true-cost-of-patient-drop-outs-in-clinical-trials/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3684189/
- https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html
- https://www.semanticscholar.org/paper/How-often-should-we-expect-to-be-wrong-Statistical-Marino/a8863fe78750e0d7fda98f8cd0f1d44b309eb188
- https://www.appliedclinicaltrialsonline.com/view/are-event-rates-and-effect-sizes-reported-accurately-in-cardiovascular-trials-
- https://www.medrxiv.org/content/10.1101/2024.06.23.24309373v1
- https://www.sciencedirect.com/science/article/pii/S2059702924013723
- https://link.springer.com/article/10.1186/s12961-025-01318-8
Let's Connect
We welcome partners from all sectors—industry, non‑profits, policy leaders, and innovators—to help build a more resilient and ethical clinical research ecosystem in Canada. Global partners are also invited for mutual learning & collaborations.