May, 2017 - SUPPORT Summary of a systematic review | print this article |

Which interventions are effective in combatting or preventing drug counterfeiting?

Drug counterfeiting is widespread globally, including in low- and middle-income countries. Counterfeit medicines may include medicines with the wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging. Counterfeit drugs need to be distinguished from substandard drugs - the latter refers to genuine medicines that failed to meet certain quality specifications.

Interventions to combat drug counterfeiting can broadly be categorized into laws and regulations, technological innovations and quality control and vigilance.

Key messages

  • Certain regulatory measures, specifically drug registration, may decrease the prevalence of counterfeit and substandard drugs. It is uncertain whether licensing of drug outlets reduces the prevalence of counterfeit drugs or the failure rates of drugs undergoing quality testing.
  • WHO prequalification of drugs may lead to a reduction in the failure rates of drugs undergoing quality testing.
  • Multifaceted interventions (including a mix of regulations, training of inspectors, public-private collaborations and legal actions against counterfeiters) may be effective in decreasing the prevalence of counterfeit and substandard drugs.
  • All studies identified were conducted in low- and middle-income countries.
  • The transferability of the findings may be influenced by a country’s existing pharmaceutical supply chain and infrastructure, the availability of routine data on drug quality, qualified and skilled personnel, and financial resources.

 

Background

It is estimated that up to 10% of all drugs sold worldwide are counterfeit, with much higher prevalences reported in regions with weak drug regulatory and enforcement systems. Counterfeit drugs can lead to treatment failures and adverse health outcomes, the development of drug resistance, and a decline in confidence in health systems. Consequently, such drugs contribute to the burden of disease and to excess morbidity and mortality.

Policymakers from low- and middle-income countries have expressed the need for effective anti-counterfeit drug strategies to be identified. This is the first systematic review to assess the effectiveness of interventions to combat or prevent drug counterfeiting. Most of the included studies did not differentiate between counterfeit and substandard drugs; instead they used “failure rate” to measure changes in quality of medicine. “Failure” referred to drugs that did not meet the minimum requirements for basic testing, quality control laboratory testing, and/or packaging analysis.

 

 



About the systematic review underlying this summary

Review objectives: To assess the evidence on the effectiveness of interventions implemented to combat or prevent drug counterfeiting, particularly in low- and middle-income countries
Type of What the review authors searched for What the review authors found
Study designs & interventions

Randomised trials; non-randomised studies (e.g. cohort studies, retrospective studies, cross-sectional studies, before-after studies); and non-comparative studies.

Any intervention at the health system level to combat or prevent drug counterfeiting. Studies that focused on internet/online drug counterfeiting, analytical techniques and medication errors were excluded. Studies that also considered substandard drugs were included only when they did not differentiate between substandard and counterfeit drugs, or where it was unclear if the poor quality medicine was counterfeit or substandard.


Designs: 21 studies with 25 comparisons: cross-sectional (17 studies); before-after (5); retrospective (1); non-comparative (1); randomised trial (1)

Interventions: Drug registration (5 comparisons); WHO prequalification of drugs (3); licensing of drug outlets (8); multi-faceted interventions (6); deployment of handheld spectrometers at the point of sale (1); a public awareness campaign (1); an international model of collaboration (1)


Problem
“Counterfeit/spurious/falsely-labeled/falsified/medicines”, as defined by WHO as medicines with the wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging.
Most of the studies did not distinguish between counterfeit and substandard medicines
Settings Any setting
Studies from low- and middle-income countries
Outcomes Changes in failure rates of tested drugs; changes in the prevalence of counterfeit medicines; changes in quality of medicine; changes in consumer behaviour; seizures of counterfeit drugs; and closures of illegal outlets/warehouses.

Changes in failure rates of drugs (19 comparisons); changes in prevalence of counterfeit drugs (4); changes in purchasing behaviour of consumers (1); confiscation of counterfeit drugs (2); closure of illegal outlet(2)

Some studies reported more than one outcome.


Date of most recent search: April 2014
Limitations: This was a well-conducted systematic review with only minor limitations. However, the included studies used largely observational designs.

El-Jardali F, Akl E, Fadlallah R, Oliver S, Saleh N, El-Bawab L, Rizk R, Farha A, Hamra R. Interventions to Combat or Prevent Drug Counterfeiting: A Systematic Review. BMJ Open. 2015; 5:e006290.

Summary of findings

Twenty-one studies reporting on 25 comparisons met the inclusion criteria for this review. All of the studies were conducted in low- and middle-income countries.

1) Regulatory measures

Ten studies with 13 comparisons examined the association between regulatory measures and changes in the prevalence of counterfeit and substandard drugs.

Drug registration 

Five comparisons focused on drug registration. This involves assessments by drug regulatory authorities of manufacturers of all components of drugs to ensure they meet international standards for good manufacturing practice before authorising drugs for sale.

 

  • Drug registration may decrease the prevalence of counterfeit and substandard drugs. The certainty of this evidence is low.
  • No studies were found on the impact of regulatory measures on the price of drugs or access to medication, particularly among marginalized groups.

Drug registration compared with no intervention

Target                 Antimalarial drugs, antibiotics, first-line anti-tuberculosis medicines, anti-mycobacterial medicines

Settings               Low- and middle-income countries

Intervention        Registration of drugs

Comparison         No registration of drugs

Outcome

Absolute effect*

Relative effect

(95% CI)

Certainty

of the evidence

(GRADE)

Without drug
registration

With drug
registration

Prevalence of counterfeit and substandard drugs

285

per 1000 

74

per 1000

(28 to 202) 

RR 0.26

(0.1 to 0.71)


(4 studies)

(5 comparisons)


Low

Difference: 211 fewer counterfeit and substandard drugs per 1000 drugs tested

(Margin of error: 83 fewer to 257 fewer)

Impact on price of drugs

No evidence identified

   

Access to generic medications

No evidence identified

   

Margin of error = Confidence interval (95% CI) RR: Risk ratio GRADE: GRADE Working Group grades of evidence (see above and last page)
* The risk WITHOUT the intervention is based on the median control group risk (28.5%) across studies from a systematic review on the prevalence of counterfeit and substandard drugs in low-and middle- income countries (Almuzaini et al, 2013). The corresponding risk WITH the intervention (and the 95% confidence interval for the difference) is based on the overall relative effect (and its 95% confidence interval).

Licensing of drug outlets

Eight comparisons focused on licensing of drug outlets. This intervention involves the authorization of pharmaceutical establishments with the aim of ensuring that the supply and sale of drugs are carried under conditions that meet regulatory requirements.

 

  • It is uncertain whether the licensing of drug outlets reduces the prevalence of counterfeit drugs or the failure rates of drugs undergoing quality testing as the certainty of this evidence is very low.

2) WHO prequalification of drugs

Three studies examined the association between drugs purchased from manufacturers with World Health Organization (WHO) approved certificates of Good Manufacturing Practices and the failure rates of tested drugs. WHO prequalification programmes refer to services provided by the WHO to “facilitate access to medicines that meet unified standards of quality, safety and efficacy primarily for HIV/AIDS, malaria, Tuberculosis, and reproductive health”.

 

  • WHO prequalification of drugs may lead to a reduction in the failure rates of drugs undergoing quality testing. The certainty of this evidence is low.
  • No studies were found on the impact of WHO prequalification on the price of drugs or access to medication, particularly among marginalized groups.

WHO prequalification of drugs compared with no prequalification

Target               Antimalarial drugs and first and second-line anti-Tuberculosis medicines

Settings             Low- and middle-income countries

Intervention      WHO prequalified drugs

Comparison       Drugs that have not met WHO prequalification

Outcome

Absolute effect*

Relative effect

(95% CI)

Certainty

of the evidence

(GRADE)

Without
WHO prequalification

With
WHO prequalification

Prevalence of counterfeit and substandard drugs

285

per 1000

31

per 1000

RR 0.11

(0.04 to 0.33)

(3 studies)


Low

Difference: 254 fewer counterfeit and substandard drugs per 1000 drugs tested

(Margin of error: 191 fewer to 274 fewer)

Impact on price of drugs

No evidence identified

   

Access to generic medications, particulalry among marginalized groups

No evidence identified

   

Margin of error = Confidence interval (95% CI) RR: Risk ratio GRADE: GRADE Working Group grades of evidence (see above and last page)

* The risk WITHOUT the intervention is based on the median control group risk (28.5%) across studies from a systematic review on the prevalence of counterfeit and substandard drugs in low-and middle- income countries (Almuzaini et al, 2013). The corresponding risk WITH the intervention (and the 95% confidence interval for the difference) is based on the overall relative effect (and its 95% confidence interval).

3) Multi-faceted interventions

Five studies reporting on 6 comparisons examined the effects of multi-faceted interventions on the prevalence of counterfeit and substandard drugs. Four of the studies focused on the ‘Promoting Quality of Medicine’ (PQM) programme which combined quality drug-testing, collaborations with regulatory authorities, and capacity building. The remaining study focused on the ‘Quality Assurance System’ (QAS) which encompassed the development of regulations, training of drug inspectors in good manufacturing and pharmacy practice, and implementation of legal actions.

 

  • Multi-faceted interventions may be effective in decreasing the prevalence of counterfeit and substandard drugs. The certainty of this evidence is low.
  • The Promoting Quality of Medicine (PQM) programme may lead to a decrease in the prevalence of counterfeit drugs or in the failure rates of drugs undergoing quality testing. The certainty of this evidence is low.
  • Implementing the Quality Assurance System (QAS) probably leads to a reduction in the proportion of drugs that are substandard (from 46% to 22%) and to the proportion of (probably counterfeit) samples with no active ingredients (from 3.3% to 1%). There is probably little or no difference between the ‘active intervention’ pharmacies, which involved two extra inspections, and the ‘regular intervention’ pharmacies in improving the quality of medicine. The certainty of this evidence is moderate.
  • No studies were found on the impact of multi-faceted interventions on the prices of drugs or access to medication, particularly among marginalized groups.

4) Other interventions

The authors identified single studies for each of the following interventions: the deployment of handheld spectrometry technologies at inspection points; an international cross-disciplinary model of collaboration; and a public awareness campaign on the danger of counterfeit medicines from illicit drug outlets.

 

  • It is uncertain whether deploying spectrometry technology for product authentication at point of sale, or applying an international cross-disciplinary model of collaboration, reduces the prevalence of counterfeit drugs as the certainty of this evidence is very low.
  • It is uncertain whether a public awareness campaign on the danger of counterfeit medicines changes purchasing behaviours as the certainty of this evidence is very low.

Relevance of the review for low-income countries

Findings Interpretation*
APPLICABILITY

The studies were all undertaken in low- and middle-income countries.

The results suggest that drug registration, WHO prequalification of drugs, and multi-faceted interventions may be effective in reducing the prevalence of counterfeit drugs.

 


The findings are applicable to low- and middle- income settings. However, a country’s existing pharmaceutical supply chain and infrastructure, the availability of routine data on drug quality, the availability of qualified and skilled personnel, and financial resources may affect the transferability of the findings.

While registration may be effective, it should probably encompass both domestic manufacturers and importers, and be complemented by routine post-marketing surveillance to maintain the quality of drugs circulating in the market.

Countries that rely heavily on imported drugs may consider opting for drugs that are WHO prequalified. However, even among WHO prequalified products, the quality may vary depending on the country of export.

Implementing multifaceted interventions requires collaboration with drug regulatory bodies, skilled human resources and technical capacity for routine drug inspections.


EQUITY
The included studies did not provide data regarding the differential effects of the interventions on underprivileged populations.

It is important to consider whether there might be differential effects of interventions according to the individual’s socioeconomic status and the baseline conditions in disadvantaged settings.

It is important to consider if the establishment of WHO prequalification programmes will lead to an increase in the prices of drugs sold to consumers as this can increase inequity, especially in settings where out-of-pocket payments for medicines are necessary.

Regulatory measures that influence access to generic drugs may have a negative impact on equity if they decrease the availability and increase the cost of medicines.

Research is needed to evaluate the potential impact of the different anti-counterfeit strategies on equity.


ECONOMIC CONSIDERATIONS
The systematic review does not sufficiently address economic consideration.

The three-level testing approach in the Promoting the Quality of Medicine (PQM) programme (a multi-faceted intervention) may be explored by regulators in settings with limited resources as a potentially cost-effective method for monitoring drugs.

Further research is needed to evaluate the costs and cost-effectiveness of the included interventions.


MONITORING & EVALUATION
The review highlights a need for methodologically rigorous studies to address the limitations of the available evidence and allow robust conclusions to be drawn about the effectiveness of interventions to combat or prevent drug counterfeiting.

Anti-counterfeit interventions should be pilot-tested with close monitoring before implementation on a large scale.

The impacts of anti-counterfeit interventions on the quality of medicines and equity should be rigorously evaluated, ideally using randomised designs. The costs and cost-effectiveness of interventions should also be examined.


*Judgements made by the authors of this summary, not necessarily those of the review authors, based on the findings of the review and consultation with researchers and policymakers in low-income countries. For additional details about how these judgements were made see: www.supportsummaries.org/methods


 

Additional information

Related literature

 

Almuzaini T, Choonara I, Sammons H. Substandard and counterfeit medicines: a systematic review of the literature. BMJ Open. 2013;3(8):e002923.

 

Coustasse A, Arvidson C, Rutsohn P. Pharmaceutical counterfeiting and the RFID technology intervention. J Hosp Mark Public Relations. 2010;20(2):100-15.

 

Karunamoorthi K. The counterfeit anti-malarial is a crime against humanity: a systematic review of the scientific evidence. Malar J. 2014;13:209.

 

Kelesidis T, Kelesidis I, Rafailidis PI, et al. Counterfeit or substandard antimicrobial drugs: a review of the scientific evidence. The Journal of antimicrobial chemotherapy. 2007;60(2):214-36.

 

Kovacs S, Hawes SE, Maley SN, et al. Technologies for detecting falsified and substandard drugs in low and middle-income countries. PloS One. 2014;9(3):e90601.

 

Nayyar GML, Breman JG, Newton PN, et al. Poor-quality antimalarial drugs in southeast Asia and sub-Saharan Africa. Lancet Infect Dis. 2012;12(6):488.  

 

Nayyar GM, Attaran A, Clark JP, Culzoni MJ, Fernandez FM, Herrington JE, Kendall M, Newton PN, Breman JG. Responding to the pandemic of falsified medicines. The American journal of tropical medicine and hygiene. 2015;92(6 Suppl):113-8.

 

This summary was prepared by

Racha Fadlallah, Fadi El-Jardali, and Elie Akl. American University of Beirut. Lebanon.

 

Conflict of interest

Racha Fadlallah, Fadi El-Jardali, and Elie Akl are authors of the systematic review on which this summary is based. For details, see: www.supportsummaries.org/coi

 

Acknowledgements

This summary has been peer reviewed by: Tim K. Mackey and Pierre Durieux.

 

The summary should be cited as

Fadlallah R,  El-Jardali F, Akl E. Which interventions are effective in combatting or preventing drug counterfeiting?  A SUPPORT Summary of a systematic review. May 2017. www.supportsummaries.org

 

Keywords

 

All Summaries:

evidence-informed health policy, evidence-based, systematic review, health systems research, health care, low and middle-income countries, developing countries, counterfeit drug, anti-counterfeit interventions



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