Compliance and risk officers in the pharmaceutical sectors now have a new report with which they can refer to in order to better inform their anti-corruption efforts.
The report, issued last month by anti-corruption body Transparency International (TI), analyzed corruption vulnerabilities and inefficiencies in the pharmaceutical sector. The report is part of the TI U.K. Pharmaceuticals & Healthcare Program, a new global initiative with an overall aim of reducing corruption and promote transparency, integrity and accountability within the pharmaceutical and healthcare industries.
Corruption in pharmaceuticals and healthcare historically has been perceived as being high. According to TI’s 2013 Global Corruption Barometer (the most recent report), 45 percent of over 114,000 people surveyed said they believe medical and health services to be corrupt. Countries that ranked as most corrupt in the medical and health services sector were Albania, Armenia, Azerbaijan, Ethiopia, Morocco, and Serbia.
In an effort to diagnose challenges faced by the pharmaceutical industry, TI’s Pharmaceuticals & Healthcare program analyzed six activities of the value chain that it considers to be high-priority areas due to the prevalence of corruption risks. “The value chain is very long. It’s very complex. There are many corruption vulnerabilities along the way,” says Sophie Peresson, director of TI’s Pharmaceuticals & Healthcare Program.
The six activities of the value chain analyzed in the TI report, with additional analysis from Compliance Week on how drug companies can apply these risks to their own practices, are discussed in further detail below.
Research and development. According to the report, one phase of R&D which is particularly vulnerable to corruption is during randomized control trials, which drug companies must carry out to prove a drug’s efficacy and safety before it can enter a market. Because drug companies rely on gaining market entry to recoup R&D costs, they may be incentivized to manipulate clinical trial data, resulting in false or exaggerated positive findings, or negative results being hidden, TI said.
At an industry level, some of the world’s leading pharmaceutical companies—including Allergan, Amgen, AstraZeneca, Eli Lilly, Johnson & Johnson, Merck, Pfizer, Roche, and many more—are working together to help detect data quality issues in clinical trials through a non-profit group called TransCelerate Biopharma. As part of this effort, TransCelerate conducted a survey of 18 member companies to assess how they are detecting data anomalies suggestive of errors, non-compliance, or misconduct.
According to the survey, commonly used strategies to detect fraud and misconduct in clinical trials were site monitoring, auditing, data review activities, and central monitoring. Advanced statistical analysis was used the least, “indicating that the biopharmaceutical industry may be lagging behind certain industries in harnessing the power and utility of these advanced methods for real-time issue detection,” the survey stated.
The survey further evaluated tactics that member companies use to detect fraud and misconduct in clinical trials. The three most common are: detecting outliers and trends (11 companies), confirmation that patients exist (eight companies), and detecting duplicate results (eight companies). Tactics used less frequently were detecting unexpected variation, measuring site performance, detecting duplicate use of source data, and examining data quality indicators.
“The value chain is very long. It’s very complex. There are many corruption vulnerabilities along the way.”
Sophie Peresson, Director, Pharmaceuticals & Healthcare Program
According to the TI report, some companies are using integrated processes and systems to proactively detect and address issues. “Advances in technology can help ease the burden on traditional manual reviews and ensure more efficient and timely identification of issues,” TI stated.
Traditional methods of detecting data quality issues, while useful, have their limitations. On-site monitoring methods, for example, can detect numerous incidents of data quality issues, but manual reviews and the inability to compare data across sites limits the effectiveness of this method. “Random quality audits also require manual review and provide insufficient coverage in terms of the small number of sites audited,” TI said.
Manufacturing. The manufacturing of safe, effective, and quality drugs depend on Current Good Manufacturing Practices (CGMPs), including quality management, appropriate packaging and labeling, assuring the appropriate strength of active pharmaceutical ingredients, testing and release.
“The way that’s done is by making sure you have a well-established manufacturing plant, trained employees, good documentation that shows what you intended to do to manufacture that drug actually was done, and that the testing that’s involved is done properly so that one can assure the quality of the drug,” says Joseph Famulare, vice president of global quality compliance and external collaboration at biopharmaceutical company Genentech, a member of the Roche Group, in its Pharma Technical Operations.
According to TI, corruption in manufacturing can occur when manufacturers pay bribes in exchange for the certification of CGMPs or as a means to create entry barriers for competitors. Corruption by manufacturers can also manifest in the deliberate lack of adherence to CGMPs, when certificates have been awarded, to increase profits.
Drug manufacturers must ensure that the appropriate active ingredients, testing, packaging, and labeling have all been followed according to a process that’s been approved before a drug is released to market, says Famulare, who also is chairman of the board of the International Society for Pharmaceutical Engineering (ISPE), a global professional association involved in the engineering and manufacture of pharmaceuticals and related products. “Only through the implementation of current good manufacturing practices can one assure that a drug will meet its quality standards,” he says.
Increasingly, regulators around the world are paying more attention to data integrity. The U.S. Food and Drug Administration, for example, recently issued draft guidance, “Data Integrity and Compliance with CGMP,” to clarify the role of data integrity in CGMP for drugs.
It’s the responsibility of the manufacturer to ensure that the results of the testing that is submitted to the FDA is accurate and truthful. “You want to make sure you’re transparent about the submission and don’t omit data that is non-favorable,” Famulare says.
Drug registration. Pharmaceutical companies know that any delay to a drug entering a market has a significant impact on the bottom line. Without proper oversight, financial pressures may drive suppliers to bribe government officials to register their drugs without meeting the necessary requirements or to speed up the registration process, TI said.
Below is a summary of TransCelerate’s Risk-Based Monitoring Methodology.
1. Central and off-site monitoring activities serve as the foundation of monitoring efforts and are complemented by targeted off-site monitoring activities based on a defined risk level, critical process and data, ongoing assessment of Risk Indicators and instructions within the monitoring plan.
2. Regardless of the monitoring approach established in the MP, monitoring activities can be increased in response to issues and risks identified, whether identified by other functions (e.g., statisticians) or during the monitor’s off-site or on-site activities. Increases in monitoring activities should be done in a temporary, targeted manner with the goal of returning to the standard level of monitoring as described in the MP. To prevent the issue from recurring, it is important to identify and address the root cause of the issue.
3. The methodology is tailored to the available technology. For example, if electronic medical records are available for remote monitoring, the monitor can perform certain activities (e.g. SDV, informed consent review) off-site (remotely).
4. Central and off-site monitoring is dependent on the timely entry of data and query resolution. Sponsors should set expectations for data entry and query response timeliness in their contracts with sites.
5. Functional oversight and associated quality documents within the IQRMP may be amended at any point in the study in response to changing risks or identified issues (e.g. in response to a protocol amendment; instructions for monitoring a new safety signal).
6. Risk-based monitoring expectations can be documented as a standard process (e.g. SOP) rather than in a functional plan in the Integrated Quality Risk Management Plan, as appropriate.
7. The methodology may be applied to all phases (Phase 1 through Phase 4), types, and stages of trials.
8. Routes of communication should be tailored to what is most effective in ensuring successful conduct of the study.
9. Risk assessments should be initiated prior to the finalization of protocols and case report forms (CRFs) to minimize risks in advance of starting the trial. Monitoring strategies are adapted to ensure oversight to what is not prevented via protocol or CRF design.
To curb corruption in the registration process, companies may want to consider establishing a few key procedures and capabilities:
A committee of experts with the necessary scientific, medical, and technical knowledge to review applications
Standard operating procedures (SOPs) and guidelines that explicitly outline the criteria for approving a drug and guidance on exemptions, fast track registration, timeframes for processing applications, and criteria for selecting external experts
Codes of conduct for internal staff and external experts, including conflict-of-interest guidelines that mandate the declaration of any relationships that may influence decision making
An accountability body dedicated to monitoring and determining an appropriate course of action for ethical misconduct
According to TI, the creation of public online databases for drugs under review and those already registered, can reduce the use of unregistered drugs and expedite the registration process. Furthermore, publishing registration approval procedures and regulatory agency product reviews on government websites can ensure that both industry and the public are aware of the registration process, TI said.
Marketing. Drug companies unethically market medicines in several ways, including by bribing healthcare professionals directly in exchange for prescribing its drugs, or providing misleading information regarding the safety and efficacy of a medicine to influence doctors’ prescribing habits and encouraging off-label, unlicensed use to increase sales.
Several marketing corruption scandals have made headlines in recent years. In one of the largest settlements, pharmaceutical giant Johnson & Johnson and two subsidiaries were ordered to pay more than $2.2 billion to resolve criminal and civil liability for promoting off-label uses of three drugs and paying kickbacks to physicians.
Some countries are now making payments between drug companies and physicians more transparent. The Physician Payment Sunshine Act in the United States, for example, requires companies to disclose in an online database the payments they have made to doctors over $10, as well as aggregate payments of more than $100 to a single doctor.
The United Kingdom similarly has enacted a mandatory “Sunshine Rule,” requiring National Health Service hospitals and physician groups to keep registers of every gift and payment given to staff from pharmaceutical companies, or risk dismissal or prosecution under the Bribery Act.
Procurement. The procurement of publicly funded medicines is particularly susceptible to corruption when it is poorly documented and weak governance is in place.
All three stages of the procurement process are susceptible to corruption:
In the pre-bidding stage, indirect procurement corruption occurs when a bid is carefully drafted so that only a predetermined company can win, making it appear as if the bid was awarded on the basis of merit without technically violating any rule or procedure
During the bidding stage, direct procurement corruption takes place when a particular winner is selected regardless of the offer through bribery or extortion of a public official in exchange for a bid
In the post-bidding stage, corruption can include false invoicing and changing contract agreements
“Open contracting is a key policy to achieving transparent and accountable procurement systems,” TI said. Open contracting allows for the collection of data on tender bids, offers of tenders, terms and conditions, contract awards, supplier performance, and prices paid.
Multistakeholder Integrity Pacts are another means to prevent corruption in public contracting, in which the government agency offering a contract and the companies bidding for it essentially agree they will abstain from corrupt practices for the extent of the contract. To ensure accountability, Integrity Pacts include a monitoring system typically led by civil society groups, usually a TI chapter.
Distribution. Distribution involves the transportation of medicines from the manufacturer to the payer. With so many touch points—including port clearing, receiving and inspecting, storage, inventory management, pickup, and transportation—the risk of corruption is high.
According to TI, policies to mitigate corruption vulnerabilities during distribution include:
Institutional checks and balances, such as dividing functions to prevent fraud;
The physical protection and security of medicines through SOPs for drug shipments and satellite tracking of delivery trucks; and
Monitoring and accountability procedures such as frequent audits and whistleblowing mechanisms for internal staff.
The adoption of appropriate technology throughout the pharmaceutical value chain can be an effective tool to minimize some of the policy and structural issues that enable corruption in the pharmaceutical sector, TI said. Technology can help prevent corrupt acts, TI added, and allows corruption to be discovered by opening health system operations to scrutiny.