Generic drug adoption framework (GRAF) adapted for Colombia: Consensus methodology

Abstract

Background: The global surge in non-communicable diseases, like cancer, strains health systems financially and restricts patient access to treatment. Generic drugs offer comparable efficacy, safety, and quality to innovator drugs, improving patient access and well-being. To aid healthcare workers in selecting the best generic drugs, Generic drug Adoption Framework (GRAF) was developed as an evaluation tool. This paper aims to adapt the tool to Colombia for healthcare professional’s daily use. Methods: Adapting the tool involved two phases: surveying healthcare workers (oncologists’ specialists and pharmacists) to gauge their readiness for adopting generic drugs, additionally and expert consensus was developed to adapt the tool to the Colombian context. Results: Of 62 surveyed healthcare workers, 38.7% were early adopters and 32.3% were late adopters. Pharmacists showed higher early adoption rates (47%) than physicians (33%). In the second phase, experts identified 12 relevant attributes for the Colombian scenario, refining descriptions and scoring scales. Conclusion: The study revealed Colombian healthcare workers’ perceptions of generic drugs and differences in adoption rates. The adapted tool to the Colombian healthcare context could clarify misconceptions that require diverse strategies to increase the use of generic drugs, aiding in better patient care.

Keywords

Medical oncology generic drugs safety profile treatment outcome antineoplastic agents drug prescription

Introduction

Non-communicable diseases are considered the leading cause of morbidity and mortality worldwide. Among these diseases, neoplasms, including cancer occupy the second place in terms of deaths and act as a barrier to improving life expectancy due to their prevalence and rapid increase among global populations.¹ According to the GLOBOCAN report in 2022, approximately 20 million new cancer cases and 9.7 million deaths were estimated worldwide. Lung cancer ranked first, followed by breast cancer and colorectal cancer. In terms of mortality, the top three places were occupied by lung, colorectal, and liver cancer.²

Looking at the numbers reported in Colombia during 2022, GLOBOCAN reported 117,620 and 56,719 deaths. Among the newly reported cancer cases, breast, prostate, and colorectal cancer are the most common in the Colombian population. In terms of mortality, lung, colorectal, and liver cancer ranked highest³

The entry of innovative therapies to treat cancer has generated improvements in survival rates and quality of life in affected patients. Nonetheless, these therapies generate a substantial financial burden on healthcare systems worldwide, creating barriers to access for many patients, especially those who live in emerging economies. This situation has generated an increasing need to develop strategies to reduce the cost derived from neoplasm treatment, making it affordable to healthcare system budgets.⁴^,⁵

One strategy devised to improve this situation is the introduction of generic cancer drugs, which are more affordable and accessible to a larger population.⁶

Although it is recognized that generic drugs are identical to the approved brand-name drug in terms of dosage, form, safety, strength, route of administration, quality, and performance characteristics⁷; unfavorable perceptions persist among healthcare professionals and patients, reducing their prescribing and use.^8-10 This situation arises from the wide array of generics available for the same molecule and the lack of practical tools enabling healthcare professionals to determine the most suitable generic alternative for prescription.

In 2018, Garg et al. conducted a survey involving 53 of physicians (oncologists) from 15 countries to comprehend their perceptions and attitudes toward generic drugs and their prescribing to treat cancer.¹¹ The results highlighted some appreciations related to quality, price, safety, and effectiveness. Looking closer at cost appreciations, 75% of the oncologists reported that a higher cost of drugs limits the treatment access for patients, also 93.9% considered that generic drugs have lower prices compared to the original drug, and 81.3% would prescribe a generic drug based on lower prices. In terms of quality, effectiveness, and safety, 85.7% of the survey group considered the effect of the generic drug depends on the company and the quality varies compared to the original drug, 74.4%.¹¹

This survey laid the groundwork for the development of the Generic Drug Adoption Framework (GRAF) project,¹² which aimed to provide a structured tool to guide physicians and decision-makers to select generic oncological drugs based on specific key characteristics (quality, effectiveness, safety, and price). Until now, in Colombia Is not available a standardized tool that allows physicians (especially oncologist) and pharmacists to qualify and stablish the key aspects to choose and prescribe high quality generic drugs to treat cancer.

In this study, we aimed to adapt the GRAF tool for Colombia using an expert consensus methodology, which will allow the implementation in the Colombian context, facilitating decision-making at the time of prescribing generic drugs for oncological patients.

Methodology

The primary objective was to adapt the original GRAF tool for use in Colombia, following the steps outlined in WO2019/145980.¹³ These steps include determining the questions for assessing efficacy, safety, quality, and cost of generic drugs, engaging in discussions with various healthcare providers regarding the framed questions, validation, and application for use in the country. This process was developed in two phases. The first phase involved applying the original tool to 62 healthcare providers to assess their perceptions and adaptability indicators (See Table 1). Subsequently, the second phase was developed to achieve consensus among 11 experts (healthcare workers in oncology institutions), who, based on the steps outlined in the patent, constructed an adaptation of the GRAF tool for the Colombian context.¹²

Table 1.

Attributes of GRAF tool.

Assessment of perceptions for generic medicines
Effectiveness	All generic drugs represent pharmaceutical products that are identical to innovator in chemical and pharmaceutical forms
	Bioequivalence/pharmaceutical equivalency reports of generic medicines are a good surrogate of effectiveness being equal to innovator
	Effect (efficacy) of the generic drug is similar to the innovator drug
	Prescribing generics, if lesser priced, will improve patient compliance
Safety	Side effect profile of a generic drug is similar to the innovator
	If the generic company supplies the same product to the United States (US), the European Union (EU), and your country, it enhances confidence on product quality
	The generics produced by different companies are always similar in quality and safety profile
	Having a structured framework on identifying high-quality generics will help you adopt and increase usage of generic drugs
Quality	A company´s generic brand when approved in a regulated country, will increase your acceptance of that brand
Cost	Low-priced generic brands from local small companies come with compromised quality
Levels for acceptance/adoption of generic medicines
Effectiveness	Sharing of clinical experience on generic drugs by peers builds your confidence in a company’s product quality
Safety	A pharmacovigilance system by a generics company in your country will build confidence on the company´s product quality
Safety	A pharmacovigilance system by a generics company in your country will build confidence on the company´s product quality
Quality	Reports establishing stability and sterility are important to identify a high-quality generic
	Track record of consistent supply by a generic company is a factor to consider before using that company´2 product
	Certificates like plant GMP (good manufacturing practices), regulatory approval certificates and others of generic drugs should be shown to get quality assurance on the product
	Personally, visiting a manufacturing facility of a generic company is needed to build confidence on the company and the quality of its products
	Receiving information on a generic company from independent third-party sources like news and media influences your decision to prescribe that company’s products
Cost	Knowledge about the price of a drug and the total therapy costs is an important factor for you to choose a generic brand
Cost	Company-sponsored patient assistance programs (PAP) are important for initiating therapy with a particular brand

GRAF tool

The original GRAF project is an international initiative aimed at assisting physicians, pharmacists, and decision-makers in transitioning from innovative drugs to high-quality generic drugs. The tool facilitates the evaluation of two key components in the process of adopting the use of generic drugs. The principal components that the tool analyzes are perceptions and acceptability indicators.¹²

The GRAF tool is composed of 20 parameters or questions and utilizes a Likert Scale ranging from zero to ten, where zero represents “Never” (0 = Never) and ten represents “Always” (10 = Always).¹²

Phase 1

The process began by administering the survey to a group of 62 healthcare workers in Colombia. The primary objective was to assess the perceptions and capacity to adapt generic drugs among healthcare workers using the GRAF tool. These professionals were selected based on their professional experience in clinical oncology, hematology, and pharmacy. The survey was conducted through a virtual platform (URL: https://www.accessgraf.org/) between November 2018 and April 2019. Participants were briefed on the study’s aim and provided consent for the use of the information provided for research purposes. The data obtained were anonymized.

The results obtained from the survey were classified into three principal groups according to the scores:

• Early adopters: composed of those who reported scores >8 in perception and acceptability indicators. This group is considered to have high confidence in adopting generic drugs in their daily practice.

• Later adopters: composed of those who reported scores <8 in perception and acceptability indicators. This group is considered reluctant to adopt generic drugs in their daily practice.

• Undecided group: composed of those who reported discrepancies between indicators (e.g., high scores in perception and low scores in acceptability).

Phase 2

Subsequently to the obtained information, the process of validation and implementation was developed using the steps recommended in the patent document. Firstly, a panel of experts convened during a face-to-face session in July 2019 to achieve consensus on defining the relevant questions to assess the attributes that compose the GRAF tool. This panel comprised different specialists in clinical sciences (oncologists, pharmacists, and hematologists). During this panel, the specialists had the freedom to determine the questions and attributes that they considered important according to the Colombian context, drawing from their knowledge and experience. Finally, those attributes that were considered relevant were included in the adaptation of the GRAF tool for Colombia.

Results

Phase 1

The survey was answered by 62 participants, of which 42 (67.7%) were physicians (oncologists and hematologists), 19 (30.6%) were pharmacists, and one person did not specify their profession. A closer examination of the results obtained from the GRAF tool indicated that 59.7% (n = 37) of the 62 participants reported high scores (average ≥ 8) in the acceptability indicator, followed by 46.8% (n = 29) who reported high scores (average ≥ 8) for the perception indicator.

According to the classification groups, 38.7% (n = 24) were classified as early adopters, 32.3% (n = 20) as late adopters, and 29% (n = 18) were categorized as part of the undecided group. In terms of professional profiles, 47% of pharmacists (n = 9) demonstrated a higher proportion classified as early adopters compared to 33% of physicians (n = 14).

Phase 2

Looking closer at phase two, the panel of experts was comprised of 11 experts, including three clinical oncologists, 6 hematologists, and two pharmacists. Subsequently, the revision of the questions that compose GRAF was under deliberation to evaluate their relevance according to the Colombian context. Finally, the panel selected 12 attributes which, in their opinion, were considered relevant and suitable for the Colombian scenario.

One of the most important changes was developed in the component and description of the attributes, such as pharmacovigilance systems, information about shortage events (reported by the company within a determined period of time), approval process by INVIMA (National Institute of Food and Drug Surveillance, Colombian drug’s regulatory agency), and also other Latin American authorities (Mexico, Argentina, Brazil, and Chile). The changes described above are found in Table 2. Additionally, the score system was changed using a Likert scale ranging zero to 2, where 0 represents “Unfulfilled”, 1 represents “Partial fulfilled”, and two represents “Fulfilled”.

Table 2.

GRAF adopted for Colombian context.

Attribute	Description of the attribute	Score 0	Score 1	Score 2
1.Pharmacovigilance	Evaluate the robustness of the pharmacovigilance system of the pharmaceutical company that produces the medicine	National pharmacovigilance system	Regional pharmacovigilance system	Global pharmacovigilance system
1.Pharmacovigilance		Collection and reporting of basic data at the country level	Collection and reporting of data in Colombia and, at least, one country in the Latin American market (Brazil, Mexico, Argentina, or Chile)	Robust data system in at least 2 countries, which may be regional or external (European Union, Australia, Japan, United States). The data must be available during the evaluation in PSUR or PBRER format
2.Timeliness and reliability of supply	-Specify the number of shortage events in the last year (openly declared by the company)	-In the last year, there were two or more product shortage events, due to alterations in the supply process	-In the last year, a product shortage event occurred, due to alterations in the supply process	-There were no shortage cases reported in the last year
2.Timeliness and reliability of supply	-Indicate the average response time for the delivery of the product to your institution from the moment you receive the order confirmation/purchase order	-Delivery time of the product to your institution> 2 business days	-Delivery time of the product to your institution between 1 and 2 business days	-Delivery time of the product to your institution, 1 business day or less
3.GMP certification	Provide a list of GMP certifications	Facility approved only by local authority INVIMA.	Facility approved by local authority INVIMA and at least one regional regulatory body (for example: Brazil, Mexico, or Argentina)	Facility approved, at least, by one of the following regulatory authorities: FDA, EMA, MRHA, TGA, PMDA
4.ISO certified	The pharmaceutical company has current ISO certification for quality management (ISO: 9001)	It is not ISO certified		ISO certified
5.Single Value proposition	Describe the characteristics of the drug that can add differential value directly or indirectly	No differential characteristics	Has a unique feature that enhances the patient experience or provides benefits for paramedical/medical/pharmacy staff	Has two or more unique features that enhance the patient experience and provide benefits for paramedical/medical/pharmacy staff
6. Certificate of use in institutions	Provide an up-to-date and complete list of the countries, where product is used	It does not have a certificate of use from institutions	Certificate of use in domestic institutions	Has certificates of use from institutions in countries in question such as: USA, Germany, France, UK, Spain, Italy, Australia, Japan
7.Pharmacoeconomic studies	Cost minimization study	No cost minimization study available		Cost minimization study is available and published in an indexed journal
7.Pharmacoeconomic studies	Have pharmacoeconomic studies been conducted comparing your product with the original drug?	No cost minimization study available
8.Post-marketing studies	Please provide details of all published or ongoing post-marketing studies for the product	None	Local study conducted at a single site	International multicenter study published in indexed journal
9.Pharmaceutical equivalence studies	Provide details of any pharmaceutical equivalency studies conducted comparing your product with the medicine in question	Pharmaceutical equivalence study not available		Pharmaceutical equivalence study available
10.Good laboratory practice certification	Provide certification of good laboratory practices for the site conducting the pharmaceutical equivalency study	There is no certificate of good laboratory practices	INVIMA certificate of good laboratory practices	Certification of good laboratory practices issued by a regulatory agency such as FDA, EMA, MHRSA, TGA, PMDA
11.Bioequivalence studies	Provide details of any bioequivalence study that compares the generic medication to the innovator drug	Bioequivalence study available and approved by INVIMA		Bioequivalence study available and approved by INVIMA or any authority: FDA, EMA, MHRA, TGA, PMDA.
12.Product registration certificate issued by regulatory bodies in question	The product has a product registration certificate issued by one of the following regulatory entities: FDA, EMA, TGA, PMDA	It is not approved by any of the regulatory bodies in question		Approved by at least one of the five health regulatory bodies in question

PSUR: Periodic Safety Update Reports. PBRER: Periodic Benefit Risk Evaluation Report. INVIMA: Instituto Nacional de Vigilancia de Medicamentos y Alimentos. ISO: International Organization for Standardization. FDA: Food and Drugs Administration. EMA: European Medicines Agency. MHRA: Medicines and Healthcare products Regulatory Agency. TGA: Therapeutic Goods Administration. PMDA: Pharmaceuticals and Medical Devices Agency.

Discussion

Access, availability, and prescribing generic drugs for oncology treatment serve as mitigation for the exorbitant cost of treatment for healthcare systems worldwide, increasing accessibility to these therapies for patients, especially in countries with emerging economies. Nonetheless, decision-makers and healthcare workers involved in the process of including and prescribing generic drugs require a standardized and rigorous process to select the best option based on high quality, efficacy, and safety.

First, we obtained the results from 62 surveys that were administered. The initial findings revealed differences among the adopter groups, especially within healthcare professions, where 47% of pharmacists were classified as early adopters compared to 33% of physicians. This finding aligns with the results reported in a systematic review conducted by Toverud et al. (2015), which also indicated differences in perceptions of generic drugs among various healthcare providers.⁸ In their study, they found that perceptions regarding the quality of generic drugs were more positively supported by pharmacists than by physicians. These discrepancies in perception are related to differences in concepts regarding bioequivalence and the understanding of control routines, requirements, and manufacturer standards imposed by the company.⁸

Similarly, Howard et al. (2017) found that specialists have a higher likelihood of prescribing brand-name drugs compared to general practitioners.¹⁴ Although our study did not administer the survey to general physicians and was only applied to specialists, this finding is similar and supports our results, where only 33% of specialists were considered early adopters to prescribe generic drugs. This result is associated with various factors such as age, experience, and the type of health insurance under which the specialists work.¹⁴ It is important to recognize that the lack of knowledge about the reasons and perceptions regarding generic drugs between general practitioners and specialists could suggest the need for further investigation in future projects.

Finally, this tool was adapted and validated for the Colombian context, assessing 12 attributes to facilitate the selection of the best generic drug, specifically for oncology treatments. Its implementation and dissemination will enable the identification of perceptions and misconceptions held by healthcare providers, decision-makers, and policymakers. The results obtained will guide interventions, such as education-based initiatives targeting healthcare providers, policymakers, decision-makers, and patients, aimed at changing perceptions of generic drugs, and increasing their utilization within the Colombian healthcare system. The increased prescribing of generic drugs could alleviate the economic burden on healthcare systems and improve access for numerous patients.

Conclusions

In conclusion, this study assessed the perceptions and attitudes of healthcare workers in Colombia regarding generic drugs in oncology clinical practice. However, the results revealed differences among health professionals in their perceptions of generic drugs. These findings necessitate different strategies, such as education-based interventions, to correct misconceptions and ultimately increase the prescription of generic drugs. Subsequently, the validation and dissemination of this tool will enable the selection of the best generic drug, considering attributes such as efficacy, safety, and cost.

Similarly, it is important to conduct new studies that explore the knowledge and perceptions of generic drugs among other medical specialties and healthcare providers. This will help to understand the reasons hindering the early adoption of generic drugs in the treatment of Colombian patients.

Footnotes

Declaration of conflicting interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Jaime Gonzalez has received funding for article processing charges from Dr. Reddy’s Laboratories. Additionally, he received support from J&J Pharma to participate in the Prostate Cancer Meeting at MD Anderson Cancer Center. Dr. Virginia Abello has received funding for article processing charges from Dr. Reddy’s Laboratories. She has also participated in advisory board meetings and received funding for participation in lectures and submission of documents to INVIMA from various pharmaceutical companies, including AbbVie, Novartis, Janssen, Pfizer, and Sanofi. Dr. Oscar Cordoba has received funding for article processing charges from Dr. Reddy's Laboratories. Dr. Kenny Galvez has received funding for article processing charges from Dr. Reddy's Laboratories. Dr. Diego Gomez has received funding for article processing charges from Dr. Reddy's Laboratories. Dr. Rigoberto Gomez has received funding for article processing charges from Dr. Reddy's Laboratories. Dr. Vanessa Ospina has received funding to attend and participate in lectures, presentations, speaker engagements, manuscript writing, and educational events from Janssen, AstraZeneca, and Bristol Myers Squibb. Dr. Carlos Varon has received funding for article processing charges from Dr. Reddy's Laboratories.

Author’s Notes

Juan Pablo Molina at the time of the research was working for Dr Reddy's Laboratories.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Dr. Reddy’s Laboratories.

ORCID iD

Jaime González

Author biographies

Jaime González, Physician specialist in Internal Medicine - Hematology and Clinical Oncology. MBA, with 15 years of experience in patient care, clinical research of new therapies and currently with a management profile in the provision of health services, in addition to 9 years of experience in trade and teaching activities, currently in search of building indicators to improve the management of cancer and hematological diseases in Colombia, generating value to the daily medical activity, based on achieving results and quality of life for patients.

Juan Molina, Doctor of Medicine (MD), clinical pharmacologist and Master in Health Economics with eleven years of experience in Medical Affairs in the Pharmaceutical Industry, of which more than eight years have been in Medical Management positions for Hematology/Oncology.

Virginia Abello, Physician specialist in Internal Medicine-Hematology. Leader of the Functional Unit Leukemia, Lymphoma and Myeloma of the Center for Cancer Treatment and Research Luisa Carlos Sarmiento Angulo, member of the board of the Colombian Association of Hematology and Oncology (ACHO) and professor for 19 years at the Fundación Universitaria de Ciencias de la Salud.

Óscar Córdoba, Pharmaceutical Chemist with specialization in Hospital Management and Master's Degree in Health Administration, in addition to a Master's Degree in Supply Chain & Logistics. With more than 25 years of experience in different hospital institutions in the country. Currently National Manager of Pharmaceutical Management at Clinica Colsanitas and professor. Extensive knowledge of the health sector in drugs and medical devices, including the management of Pharmacovigilance and Technovigilance Programs, as well as Supply Chain in Health. In summary, he has a solid background and work experience that support his managerial vision in Pharmaceutical Management.

Kenny Gálvez, Physician specialist in Internal Medicine-Hematology and specialist in thrombotic pathology, with teaching and clinical experience in the management of patients with anemia and bone marrow transplantation. He currently works as a hematologist at the Pablo Tobón Uribe Hospital in Medellin, Colombia.

Diego Gómez, Physician specialist in clinical oncology, oncogeriatrics and master in molecular biology. With over 15 years of experience in the management of elderly patients with cancer, especially lung and breast cancer, he currently serves as head of the cancer institute of the International Hospital of Colombia in Piedecuesta Santander and as a clinical oncologist.

Rigoberto Gómez, Internist Hemato-Oncologist, with more than 30 years of experience, currently working in the Imbanaco Medical Center in the city of Cali, Colombia and as a university professor in the post degree of hematology and oncology and in the post degree of internal medicine.

Vanessa Ospina, Physician specialist in Internal Medicine - clinical oncology. Practice focused on the care of oncology patients and research in Clinical Oncology, with 16 years of clinical experience and in generation and organization of projects and academic events as well as authorship and leadership of national multicenter research through the Colombian Association of Hematology and Oncology ACHO. Also with experience as a teacher.

Carlos Varón, Specialist in Internal Medicine - Hematology, with experience in the management of patients with lymphomas, multiple myeloma, acute chronic leukemia, anemias, coagulopathies and hemophilia. He currently works as a hematologist at the Institute of Oncology of the Santa Fe Foundation of Bogota.

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