Case Studies

SYSTEMATIC REVIEWS, META-ANALYSES, DATA ABSTRACTION, AND DATA CURATION

Acute-on-Chronic Liver Failure (ACLF) is a life-threatening medical condition with high mortality rates. The “Acute-on-Chronic” designation refers to patients’ clinical presentation of hepatic degeneration on top of pre-existing chronic liver disease. However, it has been felt that there is a lack of consensus surrounding the term ACLF, because there are multiple definitions for the term provided by multiple associations and organizations. Our client was interested to understand the similarities and differences across these ACLF definitions, and for this project we assisted our client by performing a comprehensive assessment of the definitions and extracting data pertaining to these definitions from 41 full texts based on the data extraction grid shared by the client. Therapy area: Gastroenterology

Ulcerative colitis (UC) is an inflammatory disorder involving large intestine in which there is formation of inflammatory ulcers in colon and rectum, that is common in North America and Europe. Many treatment options are available, but definitive treatment of non-responding cases of UC generally require surgical management. Our client was interested to develop evidence surrounding epidemiology, clinical, humanistic, and economic burden, and management options of UC. For this project, we performed data abstraction of nearly 3000 articles over two rounds of screening and identified the articles with the most relevant information pertaining to the objectives of the targeted literature review, using criteria given by the client. Therapy area: Gastrointestinal

Refractory follicular lymphoma (RFL) and marginal zone lymphoma (MZL) are two subsets of non-Hodgkin lymphomas affecting B cells. Both these types of lymphomas are rare conditions, and are often viewed as orphan diseases. For the same reason, despite contributing to a significant burden on the healthcare systems around the world, the evidence surrounding the epidemiology, clinical features, and management outcomes of these two conditions are far from complete. Our client was interested to understand the clinical, humanistic, and economic burden, treatment patterns, and epidemiology of RFL and MZL. For this project, we performed data extraction from 30 full texts and 16 study abstracts shared with us by the client, and populated the data extraction grid that was shared with us. Therapy area: Oncology

As a part of post-menopausal physiology, most women suffer from a menopause-related vasomotor symptoms (MR-VMS), including hot flashes and night sweats. While mild episodes of MR-VMS subside without treatment, moderate to severe episodes often require treatment. Most frequently prescribed therapy for MR-VMS is hormonal replacement therapy (HRT), while non-hormonal therapies are also available. Our client was interested to understand the efficacy of various available treatment modalities (HRT and non-HRT) for MR-VMS from published randomized controlled trials. For this project, we performed data abstraction of over 2700 articles over two rounds of screening and selected the most relevant papers containing the information of interest to the client, who used the same to draft a systematic review report to understand the relative efficacy of various therapies in comparison with a molecule of interest that is under development for the same indication. Therapy area: Endocrinology

Fibrosis of the liver occurs following healing of any injury to the liver, and there is replacement of healthy hepatic tissue with fibrous tissue or scar. Advanced stage of hepatic fibrosis is called cirrhosis, and is associated with significant morbidity and mortality. The important causes of hepatic fibrosis include viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis (NASH), biliary obstruction, autoimmune hepatitis, etc. Our client was interested to study the association between the stage of liver fibrosis and clinical, quality of life, and economic outcomes in Hepatitis B, Hepatitis C, and NASH through a targeted literature review. For this project, we extracted data from 38 studies identified by the client and shared the information in the prescribed format, which was used by the client to prepare a study report. For another project, we extracted data from 24 articles pertaining to information comparing traditional histological assessment of liver fibrosis with non-invasive assessment options such as biomarkers and sonography. Therapy area: Gastrointestinal, Hepatology

Breast cancer is among the most frequent cancers among women, and is associated with a considerable amount of clinical, humanistic, and economic burden. There are multiple forms and variants of breast cancer, and fortunately there are efficacious treatment options available for many of these variants. We have worked on different projects involving data curation, abstraction, data extraction and quality assessment of papers about different forms of breast cancer. Many of our projects have involved article screening and data extraction pertaining to efficacy and safety of available treatment options pertaining to triple-negative breast cancer (TNBC; screened around 3000 papers), 2nd line or later treatment of locally advanced breast cancer (LABC; screened around 1000 papers, and extracted data from 14 studies), and advanced HR+, HER2- breast cancer among pre-menopausal women, which is an under-represented population in clinical trials (screened around 560 papers, extracted data from 5 studies). We have also worked on patient-reported outcomes in addition to clinical efficacy and safety of all available treatment options for managing HER2+ or HER2+/HR+ breast cancer, especially in advanced, inoperable, or metastatic stages (screened around 6000 papers), and also on the humanistic burden of metastatic TNBC (screened around 1000 papers, and extracted data from 6 papers). For a different project, we performed search and L1 screening of around 670 papers and conference abstracts concerning epidemiology, humanistic, economic, and clinical burden of HER2+ breast cancer. All screening projects were done through 2 levels (L1: title-abstract screening, L2: full text screening) based on eligibility criteria shared by the client. Therapy area: Oncology

Streptococcus pneumoniae, also known as pneumococcus, is a gram-positive bacterium that is the major cause of community-acquired pneumonia, and also causes other serious infections such as meningitis, sepsis, and a host of invasive pneumococcal infections including otitis, bronchitis, conjunctivitis, osteomyelitis, endocarditis and cellulitis, to name a few. Routine childhood vaccination through polyvalent pneumococcal vaccines (PCV-7 and PCV-13) to prevent pneumococcal infections are recommended by the WHO, but are not incorporated in all countries yet. Our client was interested in understanding the clinical efficacy of PCV-7 and PCV-13 among children with otitis media (OM), both in clinical trial and in real-world settings, and to explore how vaccine use impacted the incidence of OM among previously healthy children. For this project, we performed data abstraction and curation of more than 650 articles through two levels of screening and identified the most relevant papers for data extraction. For a different review, we helped our client to compile evidence on the immunogenicity and clinical efficacy of PCV-7 and PCV-13 among children at high-risk of developing pneumococcal infections, in both clinical trial and real-world settings, and the impact of vaccine use on the incidence of all-cause invasive pneumococcal disease in this population, by abstracting nearly 1750 articles through 2 levels of screening, identifying the most relevant papers for data extraction. Therapy area: Infectious diseases, Vaccines

Infection by human papilloma virus (HPV) can cause genital warts, which have been known to progress to cervical, vulvar, and vaginal cancers. Vaccines of different types – bivalent, quadrivalent, and nonavalent – have demonstrated a protective role against HPV-induced genital cancer. Our client was interested to generate a systematic literature review about vaccine effectiveness of all the 3 types of vaccine in preventing HPV infection. For this project, we performed data curation through assessment of around 2500 papers in 2 rounds of screening, and identified the papers that carry the most relevant information for the SLR as per the eligibility criteria drafted by the client. For a different project, we assisted our client to understand the natural history of HPV infection, with respect to outcomes such as rates of disease progression, detection, cure, recurrence, and death, amongst both vaccinated and unvaccinated individuals, by curating over 5000 potentially relevant papers through 2 rounds of screening, and the papers that we identified as eligible were used for data extraction and quality assessment by the client. Therapy area: Oncology, Vaccines

Hemophilias are a group of inherited disorders of blood clotting wherein the coagulation cascade following injury becomes abnormal due to low amounts of clotting factors such as factor VIII (hemophilia A), factor IX (hemophilia B), and so on. While current management largely involves replacing the missing clotting factors, non-factor therapies (such as monoclonal antibodies and RNA interfaces) and gene therapy are being studied as possible therapeutic options for these disorders. Our client was interested to compile evidence surrounding the efficacy, safety, and patient-reported outcomes of factor replacement therapies and various non-factor therapies (excluding plasma derivatives and supportive therapies) for both hemophilia A and hemophilia B, in terms of bleeding rates and other surrogate markers. For this project, we screened over 2550 articles concerning both the disorders over 2 rounds of screening, based on eligibility criteria shared by the client, and identified the most relevant articles for data extraction, quality assessment, and report preparation. Therapy area: Hematology

The COVID-19 pandemic has been the major healthcare crisis that the world has witnessed in the recent years. Along with healthcare crisis, the COVID-19 pandemic was also associated with huge economic burdens. Our client was interested to conduct a systematic literature review pertaining to studies reporting the economic burden of COVID-19. For this project, we performed data extraction from a total of 48 papers identified by the client, using the data extraction grid provided to us. The data we extracted was used by the client to prepare a comprehensive study report about the economic burden of COVID-19. For a different project, we also extracted data pertaining to economic burden of COVID-19 (including direct medical costs, direct non-medical costs, indirect costs, and healthcare-related utilities) from 28 studies identified by the client.  Therapy area: Infectious diseases; COVID-19

Gastroparesis is a chronic disorder which means delayed stomach emptying without a blockage. Patients with gastroparesis present with symptoms such as nausea, heartburn, vomiting, early satiety, and boating sensation. The condition is associated with loss of quality of life, patient suffering, and economic burden resulting from reduced productivity and absenteeism. Our client was interested to generate evidence surrounding epidemiology, humanistic and economic burden, and efficacy of available treatment options for gastroparesis. We assisted our client in performing data abstraction and curation through two levels of screening of over 1600 potential articles and selected the most relevant papers for data extraction. In a different project, our client wanted to compare two diagnostic modalities used in gastroparesis evaluation, namely GEBT (gastric emptying breath test) and scintigraphy, with respect to both diagnostic parameters and patient-reported outcomes. For this project we performed data abstraction and curation of over 1200 potential articles through two levels of screening and identified the most relevant papers for data extraction.  Therapy area: Gastrointestinal

Chemotherapy-induced nausea and vomiting (CINV) is a common and debilitating side effect of cancer treatment, that is associated with a loss of appetite, leading to reduced oral intake of food and water, which further worsens the patient’s health. While numerous antiemetic agents are available, CINV continues to be an unresolved adverse effect of chemotherapy for many patients. Our client was interested to evaluate the epidemiology, humanistic and economic burden, and efficacy of various available treatment options for CINV. For this project, we screened over 1000 articles through 2 levels of screening, based on the eligibility criteria as shared by the client, and identified the most relevant papers for data extraction. Therapy area: Oncology

Acute kidney injury (AKI) is a sudden decrease in renal function, and is common among hospitalized patients. Patients who develop AKI are at an increased risk of developing chronic kidney injury. ‘Prolonged AKI’ is a less studied variant of AKI, wherein the kidney injury lasts more than 3 days. Our client wanted to understand the economic burden of prolonged AKI, compared to AKI that resolves more quickly. For this project, we screened over 2750 articles through 2 levels of screening and identified 40 most relevant papers that suited the eligibility criteria as shared by the client. We also performed data extraction from these 40 papers, the contents of which was used by the client to develop a targeted literature review report. Therapy area: Renal

Treatment options for advanced, metastatic, and ‘unresectable’ cancer of the exocrine pancreas are limited, and are often associated with poor treatment outcomes in terms of survival and quality of life. Our client wanted to generate evidence pertaining to efficacy and safety of various treatment options, including conventional chemotherapy and immunotherapy, with special emphasis on survival (overall, and progression-free), treatment outcomes (disease control rate, duration of response, overall response rate, and other parameters), and safety (adverse effects, rate of and discontinuation of medication). We performed 2 levels of article screening, and also performed data extraction and quality assessment from the eligible studies for this project using criteria shared by the client. Therapy area: Oncology

Acute myeloid leukemia (AML) is a cancer involving myeloid blood cells in which rapidly proliferating cancerous cells interfere with various normal functions of the body, including normal blood production. As an acute cancer, the condition rapidly progresses, and is fatal within few months if left untreated. AML is associated with huge clinical, humanistic, and economic burden and loss of quality of life among patients and their caregivers. Our client was interested to compare the health economic implications of AML from the perspective of four countries – Canada, Sweden, France, and USA – with respect to health economics, resource use, and impact on health utilities. We performed data extraction from a total of 55 studies pertaining to economic evaluation and resource utilization, which was used by the client to generate a detailed study report. Therapy area: Oncology

Pemphigus is a group of autoimmune disorders affecting the skin and mucous membrane that leads to blistering lesions of the affected region. Severe forms of pemphigus can result in opportunistic infections, which can lead to significant complications including death. Current treatment of pemphigus involves immune suppression through corticosteroids and other drugs, which are associated with their own complications. Our client was interested to develop an overview of the pemphigus market, including epidemiology, clinical, humanistic, and economic burden of the disease, and the merits and demerits of the existing treatment options. For this project, we assisted our client by performing data extraction of around 120 relevant papers shared with us by the client, which was used by the client to develop a document to support market access activity of a new drug being developed for pemphigus treatment. Therapy area: Dermatology

Multiple sclerosis (MS) is a disabling autoimmune disease affecting the brain, spinal cord, and nerves in there is demyelination of nerves leading to physical, mental, and psychiatric manifestations. Depending upon the extent of involvement, there are different forms of MS, such as relapsing-remitting MS, Primary progressive MS, secondary progressive MS, and clinically isolated syndrome. Our client was interested to develop a compilation of evidence surrounding the efficacy and safety of all available treatment options for relapsing-remitting MS. For this project, we performed data abstraction and screened nearly 6000 potentially eligible papers over two rounds to identify relevant papers for data extraction. For a separate project also concerning relapsing MS, we assisted our client by performing data abstraction and curation through two levels of screening of over 2400 potential articles and selected the most relevant papers for data extraction. For another project, we screened around 750 papers through 2 rounds for identifying relevant studies about efficacy of various treatment options to treat patients with active secondary progressive MS. Therapy area: Neurology

Post-operative gastrointestinal dysfunction (POGD), also referred to as post-operative ileus, is a common condition seen immediately after surgery with complex and multifactorial pathology. The condition is associated with increased patient suffering and cost of care. Our client was interested to generate evidence surrounding epidemiology, humanistic and economic burden, and efficacy of available treatment options for POGD. We assisted our client in performing data abstraction and curation through two levels of screening of over 450 potential articles and selected the most relevant papers for data extraction. In a separate project concerning the same condition, we evaluated nearly 1000 papers for eligibility as per criteria shared by the client. Therapy area: Gastrointestinal

Advanced endometrial cancer is generally associated with poor prognosis due to lack of effective treatment options which can prolong survival and achieve significant disease control. Our client was interested to compile information pertaining to the epidemiological burden of advanced endometrial cancer, treatment guidelines for the condition, the efficacy and safety profile of available treatment options for the condition, and the real-world treatment patterns for the cancer. For this project, we performed data extraction from 23 records identified by the client as containing essential information for preparing a comprehensive report. We also critically assessed the methodological quality of 53 papers identified by the client using the appropriate tool. The information that we shared with the client was used to generate a report that would support preparation of a narrative value of a two-drug combination that was being developed for launch in few global markets. Therapy area: Oncology

Chronic insomnia is associated with several physical and mental consequences, which are further responsible for loss of productivity, absenteeism, and healthcare costs. While several drugs belonging to different pharmacological classes are available for management of the condition, all of these are associated with safety concerns. Our client was interested to generate evidence surrounding efficacy and safety of all available treatment option for chronic insomnia, which would be used to support market access activities surrounding a novel drug under development for the condition. For this project, we assisted our client with data abstraction and curation through which we identified the most relevant papers for data extraction, using the criteria shared with us by the client. Therapy area: Neurology

Plaque psoriasis is a chronic, inflammatory, multi-system disease characterised by flaky, itchy, scaly skin and associated with numerous systemic complications. Effective medications for this condition include conventional drugs, and biologics, which are both more efficacious as well as more expensive. Our client was in the process of commercializing a new biologic for this condition, and wanted to generate evidence pertaining to the efficacy and safety of the existing treatment options for this condition by means of a systematic literature review and network meta-analysis. For this project, we assisted our client with data curation through two rounds of screening of all possibly relevant papers shared with us by the client, and identified the most relevant papers for data extraction and quality assessment, which was used by the client for HTA submission purposes. Therapy area: Dermatology

Varicella (chicken pox) is a vaccine-preventable infectious condition caused due to infection by varicella zoster virus. Even though varicella symptoms are mild, systemic complications are often described with relation to varicella. Our client wanted to prepare a comprehensive compilation of complications due to varicella, with a special emphasis on duration, rate of occurrence, and symptoms. For this project, we assisted the client with data curation through which 130 eligible records were identified from an initial pool of over 2000 records. We also performed data extraction, and quality assessment of the included records, and also prepared a comprehensive study report of the entire systematic literature review. Therapy area: infectious diseases

Selection of proper device for delivering inhalational drug for treating chronic obstructive pulmonary disease (COPD) is essential to ensure optimal treatment outcomes. Device selection, ease of use, familiarity, and availability are known to affect the disease progression, and even when a drug with proven efficacy is used with improper device, the disease is known to worsen. Our client wanted to update a previously prepared TLR surrounding the value of pressurised metered dose inhalers (pMDIs) in COPD and include patients with asthma as well. We updated the search strategy, screened around hits for the most relevant articles over two rounds, and extracted data from over 250 eligible papers, which helped the client to prepare a project report. Therapy area: Respiratory

Long-acting medications often tend to have poor medication adherence rates, especially if the route of administration is not oral, because of poor patient satisfaction and treatment experience. The resulting poor medication adherence can lead to poor treatment outcomes and worsening of the disease. Our client was interested to explore the role of factors such as route of administration, dosing frequency, patient convenience, and patient satisfaction on adherence to certain long-acting medications on specific indications such as hyperlipidemia, osteoporosis, psoriasis, alcohol dependence, and schizophrenia. We screened around 3800 abstracts for identifying the most relevant sources of information, based on the eligibility criteria provided to us by the client. Therapy area: Metabolic, Orthopedics, Dermatology, Psychiatry, Substance abuse

Glycogen storage disease (GSD) is a group genetic conditions in which the body cannot break down and/ or store glycogen properly, because of deficiency of various enzymes involved in glycogen metabolism. There are many variants of GSD, depending on the deficient enzyme. Treatment and prognosis depend on the type of GSD; usually dietary modification forms a predominant component of management. We have worked on different projects concerning GSD. In one instance, our client wanted to explore the incidence, prevalence, clinical manifestations, diagnostic tools, quality of life, patient reported outcomes, utility values in GSD type III (Cori’s disease) patients, by means of a targeted literature review. We developed a search strategy using PubMed, Embase and Medline (via Ovid), and extracted relevant information from 27 relevant articles as per the eligibility criteria shared by the client. In a different project, our client wanted to generate evidence surrounding the humanistic burden of GSD type II (Pompe disease), along with the clinical effectiveness and pharmacoeconomic considerations of enzyme replacement therapy for Pompe disease, which would be used for HTA submissions for NICE. For this project, we identified the most relevant papers for data extraction through two rounds of screening of nearly 2000 papers, using the criteria shared with us by the client. Therapy area: Metabolic

Non-small cell lung cancer (NSCLC) is often associated with a poor treatment outcome and high mortality. However, the presence of specific mutations in NSCLC cells has enabled the development of drugs targeting these mutations, and as a result of this, the treatment outcomes have started to improve in certain subsets of NSCLC patients. Our client was interested to develop a detailed SLR of efficacy and safety of available treatment options that target advanced NSCLC variants which carry mutations in the BRAF gene, including conventional non-targeted therapy as well as targeted therapy, from the Canadian perspective. For this project, we performed data abstraction and curation through screening of around 1100 papers through 2 levels of screening, and identified 11 eligible papers from which we extracted relevant data, which was used by our client to prepare a detailed SLR report to support market access activities of their combination product of two novel drugs for the condition. Therapy area: Oncology

Delayed graft function (DGF) is a severe form of acute kidney injury resulting from an ischemia and reperfusion injury. It is a common complication following renal transplantation from a deceased donor. DGF is associated with a significant clinical and economic burden, and is a significant determinant of long-term success after renal transplantation. Our client was interested to systematically review the available literature concerning the clinical, humanistic, and economic burden of DGF following renal transplantation, specially in the last 15 years. For this study, we extracted data from 91 articles based on guidelines and data extraction grid shared with us by the client, the findings of which was used by the client to generate a detailed study report. Therapy area: Transplantation medicine, Renal

Chronic kidney disease (CKD), also called chronic kidney failure, describes the gradual loss of kidney function. Chronic kidney disease can progress to end-stage kidney failure, which is fatal without artificial filtering (dialysis) or a kidney transplant. We have successfully completed different projects involving data synthesis concerning various aspects of CKD. In one instance, our client wanted to conduct a targeted literature review of burden of disease, epidemiology, treatment patterns, guidelines, and current trial designs and data on competitors on published SLRs and meta-analyses (MAs). A search strategy was developed using EMBASE Search Strategy (via OvidSP), Medline Search Strategy (via OvidSP), and subsequently identified the most relevant papers from around 3,800 articles over 2 rounds screening. In a different project, our client wanted to develop a systematic literature review on the general attributes of CKD, with special focus on the overall quality of life of CKD patients and the cost-effectiveness of the existing treatment modalities. We assisted by abstracting relevant information from 87 studies. Therapy area: Renal

Systematic reviews (SRs) and Meta-analyses (MAs) are considered to be the most rigorous forms of evidence, because they synthesize evidence from randomized controlled trials (RCTs) after following a robust search strategy and data curation which need to be recorded. When RCTs which have directly compared two interventions are not available, a ‘network meta-analysis (NMA)’ or ‘indirect treatment comparison (ITC)’ is performed. Our client wanted to assess the methodological quality of 26 NMAs/ ITCs in the therapy of psoriasis, using the AMSTAR-2 tool. Our team of reviewers individually assessed each paper, in duplicate, and prepared a report about the quality of each article. The inter-rater reliability was ‘near-perfect’, with Cohen’s kappa being 0.95, and mediation required to resolve only 11/416 items. Therapy area: Dermatology

Type 1 diabetes typically affects younger population, is generally due to destruction of insulin-producing beta cells in the pancreas through an autoimmune or other process, and is treated using exogenous insulin. Our client wanted to explore the in-depth natural history of type 1 diabetes, including epidemiological aspects (incidence, prevalence, mortality), progression, complications (microvascular, macrovascular, and other complications), and comorbidities, from all types of primary studies from across the globe. For this mammoth project, we performed data abstraction and curation through two levels of screening of over 14,000 articles and identified the most relevant articles to be used for data extraction and quality assessment. Therapy area: Diabetology, Metabolic

Post-traumatic stress disorder (PTSD) is a mental health condition that is triggered by stressful events. When the symptoms of PTSD (including anxiety, sensory flashbacks, emotional numbness, avoidance etc) last for over 1 month after trauma and are associated with socio-occupational environment, the condition is considered pathological. Our client wanted to explore the prevalence of PTSD in the USA, along with exploring the type of trauma and risk factors predisposing to PTSD. Particularly, the USA ve was needed for the client to assist decision-making support. We performed two levels of article screening from an initial pool of over 2,500 hits to narrow down the most suitable articles for data extraction based on the inclusion and exclusion criteria shared by the client. Therapy area: Psychiatry

Treatment options for advanced, metastatic, and ‘unresectable’ cancer of the exocrine pancreas are limited, and are often associated with poor treatment outcomes in terms of survival and quality of life. Our client wanted to generate evidence pertaining to efficacy and safety of various treatment options, including conventional chemotherapy and immunotherapy, with special emphasis on survival (overall, and progression-free), treatment outcomes (disease control rate, duration of response, overall response rate, and other parameters), and safety (adverse effects, rate of and discontinuation of medication). We performed 2 levels of screening, data extraction, and quality assessment for this project using criteria shared by the client, and the data shared by us was used for preparing a study report by the client. Therapy area: Oncology

Diffuse large B-cell lymphoma (DLBCL) is the most frequent form of non-Hodgkin lymphoma among adults, and is an aggressive malignancy with different subtypes. Treatment is often through combination of chemotherapy with immunotherapy. Relapsed/ refractory version of DLBCL has poor prognosis, and limited treatment options. Our client was interested to explore evidence from published literature pertaining to safety and efficacy of various treatment options for relapsed/ refractory DLBCL. From an initial pool of over 11,000 articles allotted to us by the client, we performed title/ abstract screening and full text screening at break-neck speed, and identified all eligible articles for data extraction. The data extracted by us was used by the client to prepare a comprehensive study report. Therapy area: Oncology/ Haematology

Atopic dermatitis is dermatitis arising in the background of allergy. Immunosuppression is an approved management option for adults and young adults suffering from moderate-to-severe atopic dermatitis. We have worked on different projects involving data curation, abstraction, data extraction and quality assessment of papers about atopic dermatitis affecting patients of different population and age groups, with different outcomes of interest. In one project, our client wanted to generate evidence surrounding efficacy and safety of different treatment options, including a monoclonal antibody acting as immunosuppressive therapy, for moderate-to-severe atopic dermatitis affecting adult patients. From an initial list of articles shared with us by the client, we identified 56 articles which fit the inclusion criteria developed by the client, after 2 rounds of screening. We also performed data extraction and quality assessment of the included papers. In another project, we assessed approximately 3800 studies over 2 rounds screening and identified 23 articles from which we also extracted data pertaining to the efficacy, safety, and patient-reported outcomes of a specific monoclonal antibody compared with conventional treatments for moderate-to-severe atopic dermatitis among paediatric age group. In a different project, we screened over 3100 papers over 2 rounds and identified 47 relevant studies from which we performed data extraction and quality assessment pertaining to the effectiveness of various systemic immunosuppressive therapies for managing atopic dermatitis. The data that we extracted helped our client to prepare two systematic reviews on the topic. Therapy area: Dermatology

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent form of polycystic disease of kidney, in which cysts form in kidneys and other organs in the body as well. This inherited disorder is difficult to treat, and can be potentially lethal. Our client wanted to consolidate comprehensive information pertaining to the epidemiology and natural history of autosomal dominant polycystic kidney disease (ADPKD) among all age groups, with specific focus on incidence, prevalence, mortality, progression and disease severity, cyst growth, end-stage renal disease, duration of disease, changes in biomarker levels, and comorbidities, with a special correlation on the mutation type. We drafted and refined the inclusion/ exclusion criteria for the systematic literature review, prepared and updated the search strategy, with appropriate inputs from the client. Subsequently, we ran the search strategy, which resulted in over 2,000 initial hits in PubMed and EMBASE, which narrowed down to around 150 eligible articles after 2 rounds of screening for data extraction. The extracted data after undergoing satisfactory quality checks from the client, and the quality assessment data as per the tool suggested by the client, were shared with the client well-within the agreed timelines. Therapy area: Renal

Parkinson’s disease (PD) is an incurable, chronic neurological disorder of largely unknown etiology, characterized by degeneration of dopaminergic neurons and the subsequent loss of dopamine throughout the brain. Advanced PD (APD) represents a progressed form of PD, characterized by symptoms that are refractory to best medical therapy. Treatment options for such patients with APD consist mainly of device-aided interventions such as deep brain stimulation (DBS), levodopa/carbidopa intestinal gel (LCIG), and continuous subcutaneous apomorphine infusion (CSAI). Our client wanted to generate evidence on the efficacy, safety, tolerability, and quality of life of these three device-aided interventions among patients with advanced PD. For this project, we screened approximately 2500 studies over two rounds of screening, and identified 29 articles which contained the relevant information. We also extracted information in the format shared by the client from these 29 articles, which was used by the client to generate a comprehensive study report. Therapy area: Neurology

Gastric cancer is the third most common cause of cancer-related death across the world. Treatment of gastric cancer generally involves surgery followed by chemoradiation therapy or chemotherapy. Our client wanted to evaluate the safety and efficacy of commonly used chemotherapeutic medications for gastric cancer management. In order to assist our client to develop a systematic review on this topic we screened around 4300 studies over 2 rounds of screening, and identified 45 studies which satisfied all eligibility criteria as required by the client. We also extracted data from these 45 papers, which helped the client to generate a detailed study report. Therapy area: Oncology

Colorectal cancer is a malignant tumor arising from the inner wall of the large intestine or rectum. Its treatment primarily depends on the location, size, and extent of cancer spread, as well as the health of the patient. Though surgery is the preferred treatment method, treatment of patients with nonresectable and resectable colorectal cancer at an advanced stage is challenging and necessitates the initiation of chemotherapy. Advances in medical oncology have resulted in the development of targeted drugs for management of such cases, using signaling inhibitors and monoclonal antibodies. Our client wanted to develop a systematic literature review on the efficacy and safety of monoclonal antibodies in colorectal cancer management. For this project, we screened over 2000 relevant papers through 2 rounds of screening and identified 15 papers which satisfied all the eligibility criteria as laid down by the client. We also extracted data from these 15 papers, which was used by the client to generate a detailed study report. Therapy area: Oncology

Disease-modifying antirheumatic drugs (DMARDs) are a group of drugs often used for the treatment of rheumatoid arthritis (RA) as they suppress overactive immune and/or inflammatory systems of the body. The choice of DMARD is dependent on a number of factors, such as the stage and severity of the joint disease, possible side effects, desired outcomes and patient preference. Our client was interested to prepare a detailed literature review to update the available body of evidence on the use of DMARDs in RA. For this project, we extracted relevant data from 45 papers as per data extraction grid shared with us by the client. Therapy area: Rheumatology

Asthma is a chronic lung disease that inflames and narrows the airways in the lungs and affects a significant proportion of individuals across the world. Our client wanted to examine the current prevalence and available treatment for this condition. We screened over 5500 studies over 2 rounds of screening, and identified 75 studies which satisfied all eligibility criteria as laid down by the client. We also extracted data from these 75 papers following the data extraction grid shared with us by the client. Our work was used by the client to draft a comprehensive systematic literature review on this topic. Therapy area: Respiratory

Overactive bladder is a condition characterized by a sudden urge to urinate (urge incontinence) and may even lead to the involuntary loss of urine (urinary incontinence). This condition is associated with significant loss of quality of life and adversely affects the social life of patients. Treatment of this condition requires identification and treatment of the cause. Our client wanted to develop a systematic literature review on patient-reported outcomes in overactive bladder. The primary focus was to understand the general perception of this condition and to determine the clinical efficacy of available treatment regimes. We assisted the client with relevant data extraction from 5 studies. Therapy area: Renal

DPP-4 (dipeptidyl peptidase 4) inhibitors are a class of oral antidiabetic agents commonly used for the treatment of type 2 diabetes mellitus (T2DM). Inhibition of DPP4 prevents incretin breakdown, leading to improved glycemic control. Our client wanted to develop a systematic literature review on the safety and clinical efficacy of DPP4 inhibitors in the management of T2DM. For this project, we screened nearly 4000 papers over 2 rounds of screening, and identified 86 eligible papers which satisfied all eligibility criteria set by the client. We abstracted these 86 papers and extracted all relevant data as per study requirement, and the information was provided to the client in a comprehensive format as a shell report. Therapy area: Metabolic, Diabetology

Age-related macular degeneration (AMD) is an acquired degeneration of the retina that causes significant central visual impairment through a combination of non-neovascular and neovascular derangement. Apart from risk factor modification and nutritional supplementation, intravitreal injections of anti-VEGF agents or laser therapy are also used for the treatment of AMD. Our client wanted to determine the prevalence and safety-efficacy profile of the available treatment regimens for AMD. For this projected, we screened nearly 3100 papers through 2 rounds of screening, and identified 47 studies which matched the eligibility criteria as set forth by the client. We also performed data extraction from these 47 studies. The data was used by the client to develop a systematic literature review. Therapy area: Ophthalmology

End-stage kidney or renal disease (ESRD) is the last stage of chronic kidney disease (CKD) leading to permanent kidney damage. Specific treatment for renal failure is determined based on the extent of the disease, overall health, and medical history of the patient. Erythropoiesis-stimulating agents (ESAs) are used for the treatment of ESRD as it maintains hemoglobin at the lowest level and minimizes transfusions. Our client wanted to conduct a network meta-analysis to evaluate the global estimate of comparative treatment effectiveness of ESAs in the management of ESRD. For this project, we screened over 6600 papers over multiple screening rounds, and identified 94 papers which matched the eligibility criteria as set forth by the client. We also performed data extraction from these 94 papers, and the information was provided to the client in a comprehensive format as a shell report. Therapy area: Renal

Graft-versus-host disease (GVHD) is major complication of allogeneic stem cell transplant used as a treatment for leukemia or lymphoma. GVDH can be life threatening. Our client wanted to develop a systematic literature review on the general attributes of GVDH, focusing primarily on the prevalence and the quality of life of the patients. We extracted relevant information from 110 studies to meet the objective.

Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer accounting for approximately 85% of all lung cancers. Mostly surgery, radiofrequency ablation, radiation therapy, chemotherapy, immunotherapy are used to treat NSCLC. The client wanted to determine the clinical effectiveness of a monoclonal antibody for the immunotherapy (both mono and in combination) of advanced NSCLC. In order to assist our client to develop a systematic review on this topic we screened approximately 1473 studies for 1st pass, 482 studies for 2nd and subsequently extracted data from 194 studies. The review was further updated next year with 1760 1st pass screenings, out of which 185 studies got into 2nd pass phase. Ninety two studies were extracted to update the SLR.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by obstructed airflow from the lungs. There are several recommendations for the management of COPD. Early diagnosis, lifestyle changes and treatment with appropriate medication can slow the progress of this condition. In order to support the global reimbursement of add-on treatment in COPD, a clinical research organization wanted to obtain the relevant economic evidence on COPD. We provided assistance by extracting data on the prior economic models, cost of illness and healthcare resource utilization from approximately 66 studies. The data abstracted was used by the client to generate a systematic literature review on the said topic.

Cytomegalovirus (CMV) is a common virus belonging to the order Herpesvirales and is globally widespread. The unique feature of this virus is that it can remain latent for long period and cause reinfection when the host is immuno-compromised. CMV is a concern for solid organ transplant (SOT) and stem cell transplant (SCT) recipients and can be life threatening. A clinical research organization wanted to develop a systematic literature review on the clinical effectiveness of anti‐CMV agents in the treatment of CMV infected individuals who have undergone solid organ transplantation (SOT) or stem cell transplantation (SCT). We provided assistance by abstracting relevant information from 85 studies.

Chronic kidney disease (CKD) is a condition characterized by gradual loss of kidney function over time. CKD is prevalent among the elderly population and associated with an increased risk of cardiovascular disease and chronic renal failure. It is a global health burden with a high economic cost to health systems. Our client wanted to develop a systematic literature review on the general attributes of CKD, with special focus on the overall quality of life of CKD patients and the cost-effectiveness of the existing treatment modalities. We assisted by abstracting relevant information from 87 studies.

Metastatic breast cancer is unlikely to be cured, but there have been meaningful improvements in survival due to the availability of more effective systemic therapies, including endocrine therapy in the treatment of hormone-sensitive disease. Breast cancer can be further broken down into three subgroups and can be directed according to there treatment choices: 1) the estrogen receptor (ER) expression, 2) the human epidermal growth factor receptor 2 (HER2 [with or without ER expression]), and 3) triple-negative. Patients with ER-positive metastatic breast cancer often respond to endocrine therapy alone or in combination with targeted agents, which can reduce tumour burden and symptoms with generally fewer side effects and toxicities than chemotherapy. Our client wanted to determine the safety and efficacy of existing chemotherapy for breast cancer. In order to assist our client to develop a systematic review on this topic, we screened 1000 studies for the 1st pass and 200 studies for the 2nd pass.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality both in the United States and worldwide. The usual treatments for patients with NSCLC, such as advanced lung adenocarcinoma, are unspecific and aggressive and include lung resection, radiotherapy and chemotherapy. Recently, treatment with monoclonal antibodies and biological inhibitors has emerged as an effective alternative, generating effective results with few side effects. Our client wanted to evaluate efficacy and safety of a monoclonal antibody in combination with radiotherapy in patients with advanced NSCLC. We extracted relevant information from 100 studies to meet the objective.

Rotator cuff tears (RCT) are one of the most frequent shoulder diseases and their incidence increases with advancing age. The tendons of your rotator cuff can tear much like a piece of leather. Sometimes, the tendon is only slightly damaged or irritated. Sometimes, the tendon has a complete tear, which means that the tendon has torn away from the bone. Tears of the rotator cuff tendons may cause shoulder pain and can limit shoulder function. Our client wanted to determine the effectiveness of available treatment on Rotator cuff repair. We extracted relevant information from 40 studies to meet the objective.

MARKET ACCESS AND VALUE STORY DEVELOPMENT

Lower urinary tract symptoms (LUTS) affects both men and women, and is a sign of urinary tract obstruction due to various causes. Uroflowmetry and bladder diary are two modalities used in the evaluation of moderate to severe LUTS. Our client was interested to develop a model to forecast the number of patients with LUTS in the USA over the next five years, which would be used to predict the number of users of uroflowmetry and bladder diary over the time period. We developed a tool to cater to these requirements, and using the same, we developed a detailed report summarising the disease burden of LUTS in the USA, market size (present and future), pricing and reimbursement market analysis, and competitor landscape for both uroflowmetry and bladder diary, with a prediction in the number of urologists who may adopt these technologies in the next 5 years. This report was used by our client to prepare market access and pricing-reimbursement strategies.

We assisted our client to develop certain key performance indicators (KPIs) which would help the client to objectively assess and quantify the quality of care provided to patients undergoing certain orthopaedic surgeries. Using the KPIs developed by us, the client would ‘score’ the quality of care by the hospital, and objectively assess the lacunae in order to rectify them. For this project, we developed the KPIs, and also provided the client with a framework to capture data for calculating the KPIs. The KPIs developed by us took into consideration both hospital-related parameters (such as duration of hospital stay, infection post-surgery, etc) as well as patient-related outcomes (such as pain, patient satisfaction, activity limitation, etc). Subsequently, we also analysed the KPIs and generated a comprehensive report which was used by the client for benchmarking the services provided by hospitals which practiced value-based healthcare delivery.

One of our clients wanted to understand the potential to expand access & reimbursement in “Second Tier” markets in India for a mature oncology biologic drug (not immuno-oncology), which is endorsed by international guidelines for 1L use in select cancers. We helped the client in explaining about the level of utilization and reimbursement of biologics in general in the specific markets (not necessarily in oncology), incl. compliance to international guidelines, recent and future landscape changes (including HC policy) that might have an impact on the oncology treatment landscape and specific market access and reimbursement challenges and opportunities relevant for oncology (tendering, level of formularies, budget caps) in India. The findings were shared in the form of a brief report.

Primary liver cancer encompasses Hepatocellular carcinoma (most common primary malignancy of the liver), Cholangiocarcinoma (<10%), and some other rare histologic types. Liver cancer is the 5th most common cancer and the 2nd most frequent cause of cancer-related deaths globally. Current treatment options for HCC are majorly dependent upon the tumor size and include surgical resection, liver transplantation, thermal ablation and chemoembolization. Our client wished to enter this therapeutic domain with an innovative product that uses LTSL (lysolipid thermally sensitive liposome) technology to encapsulate Doxorubicin, a proven and commonly used cancer drug. With the product, that was being evaluated in a global phase 3 clinical trial for the treatment of primary liver cancer, the client wanted to seek further clarity and understanding of the HTA scenario in China – considered to be as one of the most important markets for there product. We helped them by liasoning with China HTA experts and creating HTA landscape assessment report along with oncology specific information. We also provided case studies of products, which got successful market access in China in last decade.

Multiple myeloma is a common hematologic malignancy that has been on rise in Asian countries. Our team aided a pharmaceutical client in generating evidence to demonstrate and support the value of a drug (a selective proteasome inhibitor) for the treatment of multiple myeloma in certain Asian nations. To strengthen the value story, we gathered relevant information through extensive literature search. Approximately 2384 studies were screened for 1st pass, 278 studies were screened for 2nd pass and data was abstracted from 56 studies. Additionally, we developed the value story of the pharmaceutical product of interest based on the data that characterized natural history of disease in the particular Asian locations, burden of illness in those regions, common patterns of care, unmet or under-addressed medical need and benefit-risk profile of the desired pharmaceutical agent

HEOR AND MODELLING PROJECTS

Novel treatment modalities are being developed for treating pancreatic cancer, which has as such a poor prognosis. One such novel modality involved a combination of a chemotherapy drug with a novel drug delivery system through a specially designed catheter. Our client was interested to understand the budget impact and impact on reimbursement of different pricing strategies for the combination, which was granted orphan drug status by the USFDA. We developed a detailed budget impact modelling analysis dissecting the value proposition, reasoning, and risks associated with different price corridor for the combination, for targeting the US market. For doing this, we considered multiple perspectives (insurer, manufacturer, and hospital) and determined the best possible pricing strategy for the manufacturer with best ICER, based on evidence from previous studies, competitor pricing, and current and future reimbursement scenario in the US.

Stigmas associated with HIV in Saudi Arabia have resulted in an increased clinical, humanistic, and economic burden on the country’s healthcare resources. Interventions such as prevention of mother to child transmission (PMTCT) and HIV self-testing (HIVST) might address some of these stigmas and increase diagnosis and treatment of HIV. Client developed a health economic model (Markov model) to estimate the cost-effectiveness of stigma-addressing interventions to improve diagnosis and treatment of HIV from a societal perspective in a KSA setting, using data from various external sources. The stigmas related to having unprotected sex, testing for HIV infection as a member of a risk group, and seeking treatment if infected, were included in the model. It was found out in the research that both PMTCT and HIVST are costing saving stigma-addressing  interventions for PLHIV in KSA. We helped the client in manuscript preparation for the purpose of publication.

The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is high in the Middle East; however, there are no approved therapies currently available for these conditions. The client developed a health economic model (Markov model) to estimate the current and future clinical, economic and humanistic burden of NAFLD/ NASH in KSA, UAE, and Kuwait, from a societal perspective. Model input data was obtained from population projections from previous studies and UN data. Transition probabilities were calculated after extracting data from similar studies in the past using a graph digitization software. Country-specific costs incurred in the treatment of NAFLD (including medication, medical management, and healthcare procedures) and utility inputs were obtained from local experts. The costs, QALYs and LYs associated with each health state were calculated for all three countries. It was found out that NAFLD/ NASH is associated with substantial clinical, economic, and humanistic burden in the KSA, UAE and Kuwait. We helped the client in creating manuscript from the model report provided to us.

We helped our client to conduct the targeted literature review/secondary literature search to capture information related to Treatment Resistant Depression (TRD) for GCC region (KSA, UAE & Kuwait) and Emerging Markets (Egypt, Algeria, Lebanon & Turkey). We further helped them to build a universal economic model from scratch to assess the over all economic burden (considering direct and indirect cost) of TRD from payers’ and societal perspective and assisted in developing questionnaire for expert interviews to address the gaps identified in the literature search and to populate/validate the model/(s). The model was adapted by populating it with local data specific for each country. The outcome findings were consolidated in the form of white paper and manuscript.

While hospitals remain the most common place of death in many western countries, specialised palliative care (SPC) at home is an alternative option to improve the quality of life in their final days of life. This manuscript is a full economic evaluation (Cost-utility analysis) of an accelerated transition to home for incurable cancer patients in need of palliative care. The analysis is performed from a societal perspective within a randomised controlled trial – the Danish Palliative Care Trial (DOMUS). The researchers looked outcome in the form of incremental cost-effectiveness ratio (ICER) and found out that accelerated specialised palliative care and psychological treatment yields better QALYs than usual care with a large increase in costs. Based on usual willingness-to-pay thresholds, the intervention is not found to be cost-effective relative to usual care. We helped the client in manuscript editing and making it publication ready.

Venous thromboembolism (VTE) is a disease that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). Treatment primarily aims at preventing pulmonary embolism (PE), reduce morbidity, and minimize the risk of post-thrombotic syndrome. So far the mainstay of medical therapy has been anticoagulation. A pharmaceutical company wanted to compare the cost-effectiveness of two anticoagulant drugs used for the treatment and prevention of VTE. The source document and the manuscript outline were provided to us and we assisted our client with drafting the manuscript. The abstract of the manuscript was presented at a conference.

In India, the average cost of cancer treatment ranges from Rs. 2.5 L to Rs. 20 L for six months leading the families into huge economic burden. On the demand of one of our clients,, the information was gathered on the sources of funding for cancer; the services availability in hospitals and clinics; government and non-government schemes for cancer; the process of incentivizing the healthcare providers; the role of drug manufacturer, wholesalers, distributors and providers in drug costing; and reimbursement strategy for cancer treatment in India. It also reports on the complications Indians are facing during cancer treatment.

REAL WORLD EVIDENCE/ORIGINAL RESEARCH

Anticoagulation is an essential component in the management of patients having non-valvular atrial fibrillation (NVAF). While vitamin K antagonists such as warfarin have been traditionally used for this purpose, newer oral anticoagulants have created interest among clinicians since they do not have pharmacologic disadvantages that are seen with warfarin and are associated with better treatment outcomes. Our client wanted to explore the patient’s perspective of treatment with warfarin versus a newer anticoagulant in a real-world setting, and had executed a prospective study involving over 900 patients from 5 countries in the South East Asian region. For this project, we actively participated in an investigators’ meet to understand the manuscript requirement, and drafted the research manuscript based on the corporate study report shared by the client. The project resulted in two high-quality manuscripts, one of which is already published in an indexed journal, and the second undergoing review.

Transfusion-transmitted infections (TTIs) are one of the biggest fears to blood transfusion safety. Nucleic acid testing (NAT) in blood donor screening has been implemented in many countries to reduce the risk of TTIs. Our client’s objective of this observational study was to assess the ability of NAT to detect hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) from donor blood samples declared seronegative. Every donor blood sample was screened for HBsAg, anti-HCVnti-HIV-1, anti-HIV-2 and p24 antigen by electrochemiluminescence assay. All initial serology non-reactive samples were subjected to NAT discriminatory assay for HBV, HCV and HIV. It was found out that the routine utilization of MP-NAT testing for HBV, HCV and HIV-1 has the potential to improve the efficacy of screening for protecting blood recipient from TTIs. It enables detection of these viruses, which were undetected by serological test and thus helping in providing safe blood to the patients. We assisted the client in preparing the manuscript for the purpose of publication.

Down’s syndrome is the most common type of chromosomal abnormality found in neonates. It is associated with characteristic abnormal facial features and mental retardation. However, clinical diagnosis is not sufficient to confirm the disease. Classical karyotyping has long been used as diagnostic tool for confirming Down’s syndrome. Our client conducted a study to confirm the cytogenetic composition of individuals suspected with Down’s syndrome after the preliminary clinical diagnosis in Basra, Iraq. We helped the client in manuscript preparation, which is due for publication. Study provided the basic information required to forecast the various complications associated with Down’s syndrome.

Gastric cancer is one of the leading causes of cancer-related deaths across the world and in the Middle East. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression has been observed in gastric cancers. Trastuzumab, a recombinant monoclonal antibody targeting HER2 protein, is now being used for treatment of metastatic gastric cancer. Our client wanted to study the frequency and association of HER2 overexpression with age, gender, histopathological subtype and grade of differentiation in patients with gastric adenocarcinoma. It was a cross-sectional single-centre study. Demographic (age, gender), histopathological (histological subtype, grade of differentiation) and immunohistochemical (HER2 overexpression status) data from 100 consenting adult patients (male: 56) with histopathologically confirmed gastric adenocarcinoma from samples obtained through endoscopy or surgery was collected. We helped the client in preparing the manuscript. It was found that HER2 over-expression was 6% in the population; statistically significant correlation was found with histological grade. Manuscript is still under peer-review.

Co-morbidities are known to have a strong negative association on Overall Survival (OS) of chronic diseases. Charlson Co-morbidity Index (CCI) is one of the known tools to measure the impact of co-morbidities on disease outcomes including leukemias. The researchers aimed to study the effect of co-morbid conditions on the OS among CML patients on tyrosine kinase inhibitors (TKIs) using CCI. It was a retrospective study conducted among patients with CML, treated at Basra Oncology and Hematology Center (Iraq), between year 2006 and 2016. The CCI was calculated using patients’ information taken from hospital records. Patients were divided into two groups – Group 1 (CCI1) included patients with low co-morbidity index of 2 and 3; and Group 2 (CCI2) included patients with high co-morbidity index of 4 and more. Overall survival (OS) probabilities were calculated using Kaplan-Meier curves. It was found out that there was no significant correlation between CCI and OS among CML patients. Diabetes mellitus was the most commonly found co-morbidity among CML patients. We helped the researchers in preparation of manuscript, which is due for publication.

Adequate information about cancer incidence is used to estimate the size of problem, which is crucial for managing and preventing cancer. The client undertook the study to report the incidence and pattern of various types of cancers and their distribution across demographics in Basra, Iraq in the year 2017.  Cancer cases recorded during 2017 at the Basra Cancer Control Centre and Department of Pathology and Forensic Medicine were included in the study along with the cases registered at Basra Oncology and Haematology Centre, Children Basra Hospital and other private laboratories. We analysed the patients’ records including age, gender, region of residence and type of cancer. Percent of incidence for different geographical region was also reported. Distribution of incidence across age groups was reported as percentages. The mean age with standard deviations were reported for patients of different genders and age groups. Incident rate per 100,000 population was calculated for different types of cancer. The findings of the research were put in the form of original manuscript, that has been sent for publication.

Vitamin D deficiency has often been linked to chronic low back pain (CLBP). In many patients, vitamin D deficiency remains undiagnosed therefore untreated leading to persistent, musculoskeletal pain as observed in CLBP. So far no prospective studies have focused on the prevalence of vitamin D deficiency in Indian patients with CLBP. The client wanted to determine the prevalence of vitamin D deficiency in Indian patients and its role in CLBP. Data were obtained from a controlled, open label, single arm clinical trial that assessed the effectiveness of vitamin D supplementation in patients with CLBP. The study was conducted in an outpatient pain clinic of a tertiary care hospital. The findings were reported in accordance with the STROBE (Strengthening the Reporting of Observational studies in Epidemiology) guidelines. Pain and functional disability was determined. Chi-square test and independent t-test was used for the categorical and continuous variables, respectively. Multivariate logistic regression model, univariate analysis of variance (ANOVA) and post hoc Bonferroni test was also used for statistical analysis. The study revealed increased prevalence of vitamin D deficiency among Indian patients with CLBP and indicated the importance of determining the vitamin D status for effective management of CLBP.

Diabetes affects a major proportion of the Indian population. Single anti-diabetic agents are not always effective in controlling this condition. Our client wanted to determine the combined effectiveness of two anti-hyperglycemic agents with complementary mechanisms of action in managing diabetes. An open, prospective, multicenter, single-arm, non-interventional study was conducted across several sites in India. The study was registered under the ClinicalTrials.gov and the Clinical Trial Registry of India. Postprandial glucose, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were measured to determine the clinical effectiveness of the drugs. This study found that the combination of the two anti-hyperglycemic agents was well tolerated, safe and efficacious in Indian patients and could be considered a treatment option for diabetes management.

Hyperglycemia over a prolonged period can damage peripheral nerves and result in increased risk of hand and foot ulcers even resulting in amputations. Such peripheral nerve dysfunction is referred to as diabetic peripheral neuropathy (DPN), a major complication of type 2 diabetes mellitus. While several studies have focused on the prevalence of DPN among the Western population, there is limited data on the prevalence of this condition among the Asian populations, specifically the north Indian population. Our clients not only wanted to assess DPN prevalence in general but also compare the prevalence among populations with established diabetes mellitus and newly detected diabetes mellitus. They also wanted to identify the associated risk factors and possible sex-specific variations. A cross-sectional epidemiological study was conducted at a tertiary care hospital. Student’s t-test, Mann–Whitney U-test or χ2-test, multivariate logistic regression and Kaplan–Meier survival curves were used as a part of the statistical analysis.  The study indicated a high prevalence of DPN among the type 2 diabetes mellitus patients and indicated the importance of early diagnosis and timely screening to prevent DPN progression.

Topical non-steroidal anti-inflammatory drugs (NSAIDs) are a preferred over topical steroids to control inflammation post cataract surgery and a preservative-free variation is considered the most effective. While the clinical effectiveness of the preservative-free NSAID in reducing cystoid macular edema (CME) and macular thickening in patients with cataract surgery is well established across many countries, its safety and efficacy was not studied in Indian patients. The client wanted to evaluate the safety, tolerability and efficacy of the preservative-free NSAID in controlling inflammation in Indian patients who were subjected to cataract surgery. A retrospective, open-labeled, single-arm study was conducted and data was obtained from the records of 96 cataract patients. The results confirmed that the preservative-free NSAID successfully reduced ocular inflammation and was well-tolerated in patients after cataract surgery.

Early Nutritional Support is considered important for ICU management. Previous observational studies have indicated adverse clinical outcomes as a consequence of cumulative calorie debt. Our client hypothesized that early and goal directed enteral nutrition (EN) support to meet the calorie debt could lead to better outcomes. A retrospective observational study was conducted at a multidisciplinary ICU in a tertiary health care facility in India. The data obtained indicated that early initiation and goal directed EN could improve clinical outcome and thus aid in effective ICU management.

Diabetic nephropathy can lead to end stage renal disease (ESRD). Patients with chronic kidney diseases are put on low protein and very low protein diets to improve associated metabolic disorders and uremic symptoms. However, it is important to ensure that the diet fulfills the essential amino acid and energy requirements of the patients.  Our client wanted to determine the efficacy and safety of low protein diet supplemented with keto-analogues of essential amino acids and its superiority over low protein diet without such supplementation. A randomized control trial was conducted at a reputed hospital in Mumbai and a total of 48 patients with diabetic nephropathy were included in this study. The demographic features, post-treatment survival probability etc. were studied. The results suggested the clinical effectiveness of supplemented low protein diet in delaying kidney complications that leads to ESRD. Additionally, the supplemented diet was found to be safe, improve metabolic conditions, and met the nutritional requirement of the patients

Treatment with chimeric mAb often results in the formation of human anti-chimeric antibodies (HACA) that may worsen the condition in axial spondyloarthritis (AS) and rheumatoid arthritis (RA) patients. In this case, our client’s KOL wanted to investigate the effect of infliximab therapy on both AS and RA patients. We did the data analysis and manuscript writing for the client. It was found that HACA was formed in AS patients treated with infliximab, but not in RA patients following same treatment. HACA-positive AS patients treated with chimeric mAb showed a higher post-treatment disease activity as measured by BASDAI and were associated with lesser post-treatment reduction in BASDAI than HACA-negative patients.

CASE SERIES

Autoimmune inner-ear disease (AIED) is a rare autoimmune disorder characterized by progressive hearing loss. Of the several medical therapies proposed for the treatment of AIED, corticosteroid therapy is considered the most effective. Commonly tumor necrosis factor-α inhibitors are administered in combination with corticosteroids for favorable outcomes. The client examined the use of a popular anti-TNF drug in an AIED patient who developed inflammatory polyarthritis (IPA) and was non-responsive to therapy with steroids. The findings confirmed that the anti-TNF agent was successful in managing IPA in the patient with AIED.

Hidradenitis suppurativa (HS), also known as acne inversa, is a rare and long-term skin inflammatory condition diagnosed by small and painful swollen lumps, typically affecting the armpits, the groin, area between the buttocks, and under the breast. The unresponsive routine multiple treatment modalities necessitated a more efficacious treatment for HS. On demand of our clients, the effect of a novel TNF-α inhibitor was studied on two adult patients who were severely affected by HS (Hurley stage III). These two cases were the first of its kind demonstrating the success of this particular TNF-α inhibitor treatment on patients of Indian origin suffering from HS.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a delayed type of systemic hypersensitivity reaction caused by the intake of anti-convulsants, allopurinol, sulfasalazine, NSAIDs and other drugs. It is characterized by maculopapular rashes, fever and eosinophilia affecting the systemic features. This syndrome is severe and fatal than acute drug reaction as it affects internal organs as well. Intake of certain antibiotics, especially the β-lactams such as amoxicillin, may trigger the reaction in the patients of DRESS syndrome. Our client needed a case study for their KOL on a patient who was suffering from DRESS syndrome induced by sulfasalazine and aggravated by ceftriaxone. A prompt withdrawal of sulfasalazine along with intake of systemic corticosteroids and N-acetyl cysteine was found to be useful for a such life-threatening condition.

REVIEWS

Milk intolerance and milk allergy are two different conditions that are often used interchangeably, albeit erroneously. Milk intolerance arises due to deficiency of lactase enzyme, whereas milk allergy is an immunologically mediated condition. Our client wanted a comprehensive narrative review surrounding these two topics, which also touched upon alternatives to cow’s milk, recommendations from reputed bodies regarding use of these alternatives, and the role of modified infant formulas for infants who need milk supplementation but are having milk intolerance and/ or milk allergy. At the end of the review, we found out that though most guidelines recommend milk alternatives such as extensively hydrolyzed milk formula and amino-acid based formula, they suffer from palatability and cost. On the other hand, modified goat’s milk-based formula likely has nutritional profile and growth outcomes among infants that is comparable with cow’s milk. Therapy area: Nutrition and Dietetics

Threatened miscarriage and recurrent miscarriage are two frequent complications of pregnancy, which have been associated with lower levels of progesterone in circulation. Our client wanted a thorough review about the role of different types of progesterones in the management of these two conditions, with a special emphasis on dydrogesterone. Our literature review found out that dydrogesterone, a retroprogesterone that is produced from a natural source, has favourable pharmacokinetic profile, is well tolerated and has a favourable safety profile in all approved indications. It is safe in pregnancy, and is not associated with any adverse maternal or foetal outcomes attributable to teratogenicity. The efficacy, safety, and tolerability profiles of dydrogesterone have been extensively investigated, with favourable results in numerous large-scale RCTs and meta-analyses. Therapy area: Obstetrics and Gynaecology

Bone turnover markers (BTMs) are key tools in monitoring the effect of anti-resorptive and anabolic therapies against bone pathologies. These tools assist in the management of osteoporosis therapy and predict the associated risks such as, the elevated bone turnover rate could indicate the bone pathologies. International Federation of Clinical Chemistry and International Osteoporosis Foundation have proposed serum C-telopeptide cross-links of type I collagen (CTX-1) and procollagen type 1 amino-terminal propeptide (P1NP) to be used as reference markers for bone resorption and bone formation, respectively. The BTM outcomes could be affected by the uncontrollable factors such as age, gender, pregnancy, menstruation, excess or under mobility, recent fracture, co-morbidities, and medications. We did a thorough literature search to bring the review on the above mentioned topic. We found out that the assessment of BTMs is crucial in elderly patients when adherence with and persistence to the therapy is essential to increase the efficacy of drugs. The advancement of BTMs in clinical and research settings of bone metabolic diseases treated with anti-resorptive and anabolic therapies were described in this review. Therapy area: Rheumatology

India ranks as one of the highest contributors to the global diabetes mellitus (DM) pandemic, with 65 million people i.e. 17% of global 382 million diabetics, residing in India. Diabetes imposes serious threat on overall health status of an individual and can be a risk in itself for multiple chronic and life-threatening diseases such as myocardial infarction, stroke, metabolic syndrome etc. Despite the growing concern regarding DM and its socioeconomic burden, diabetes control in India is far behind what is ideally expected. The mean hemoglobin A1c of diagnosed population is 9.0% – at least 2.0% higher than what is suggested by international bodies. The main objective of this article was to understand the scenario of diabetes in India with respect to its prevalence rate and future disease burden. Our client further aimed to determine the status of diabetes care and management in terms of available facilities, point of care, cost of treatment, various points of intervention and involvement of the non-governmental organizations. They further assessed the awareness level, screening and treatment initiatives for DM within the country with a focus on programs conducted by government bodies and finally reviewed the financial aspect in terms of source of funding and proportion of patients who can afford the treatment. We helped in creating this very interesting white paper for the purpose of publication, out of the information provided to us in the form of power point presentation. Therapy area: Metabolic, Diabetology

Vitamin D deficiency is a common occurrence and has been linked to several medical conditions including rickets in children to osteoporosis in adults. It also contributes to diabetes, metabolic disorders and cardiovascular disease. Our client wanted to review the pathophysiology of vitamin D deficiency and the associated clinical complications. A detailed review indicated the requirement for novel guidelines on Vitamin D supplementation to achieve better treatment outcomes, improve morbidity and patient health. Therapy area: Metabolic

Toxic reactive oxygen species (ROS), such as hydrogen peroxide, organic hydro peroxides, nitric oxide, superoxide and hydroxyl radicals etc. are constantly produced under physiological conditions and results in oxidative stress. The resultant imbalance in pro-oxidant/antioxidant homeostasis is responsible for the pathogenesis of different diseases. Our client wanted to obtain clinical evidence from global studies on the critical role of ROS in deteriorating human health and the importance of superoxide dismutase (SOD) in ameliorating the ROS toxicity. Electronic databases (Medline, Pubmed) were searched to identify relevant studies (peer reviewed case studies, observational studies, case control and cohort studies). Extensive data suggested the major role of ROS in the causation of several diseases. It also indicated that in order to maintain defense against ROS, SOD as an exogenous source would be necessary for anti-oxidative defenses.

Diabetic individuals are at increased risk of peripheral arterial disease and neuropathy. Long-term diabetes can cause nerve damage and poor blood flow leading to diabetic foot (DF). It is a major complication that increases the risk of infection, gangrene and amputation in affected individuals. Our client wanted to review the recent advances and evidences that could improve DF management. Medline and PubMed were searched for relevant information (peer reviewed case studies, observational studies, case control and cohort studies) on DF as a major complication of diabetes. Data obtained indicated major gaps in novel approaches for DF prevention. It was concluded that appropriate awareness regarding diabetes related foot complications, importance of footwear and  regular checkups can help to reduce diabetes related DF. Therapy area: Metabolic, Diabetology

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age. Our client wanted to summarize the underlying causes and common symptoms of PCOS and suggest suitable guidelines for effective management. It was evident that successful treatment of PCOS required proper diagnosis. Therapy mostly depended on the symptoms, age and future pregnancy plans. It was concluded that with accurate diagnosis, appropriate lifestyle interventions, and suitable PCOS treatment (birth control pills to regulate menstruation and insulin-sensitizing or androgen-blocking medications), this medical condition and the associated overwhelming health problems can be controlled. Therapy area: Endocrinology

Telangiectatic osteosarcoma (TO) is an uncommon variant of an intramedullary high grade osteosarcoma that accounts for 2.5-12% of all osteosarcomas. There is limited understanding regarding the incidence, clinical presentation, treatment, and prognosis of this medical condition. The client wanted to systematically study the available literature to obtain detailed information on this high grade osteosarcoma. Literature review revealed poor prognosis of TO patients in earlier studies, however, recent use of neoadjuvant chemotherapy with surgery was reported to improve survival rates of the patients. The finding of this study corroborates the importance of early diagnosis and optimal treatment for improved outcomes. Therapy area: Oncology

The hypoglycemic efficacy of dipeptidyl peptidase-4 inhibitor has been demonstrated as monotherapy or in combination of other anti-hyperglycemic drugs. The SAVOR-TIMI 53 trial have raised the concerns about the increased risk of hospitalization due to heart failure following this particular dipeptidyl peptidase-4 inhibitor administration. As per the demand of our clients, all the relevant research articles along with reviews and other data was systematically reviewed.  This systematic study showed that increase in hospitalizations due to heart failure have not been demonstrated by other trials as well as by real-world data analyses from insurance claims data involving a huge number of patients. The vast available evidences favour the clinical usage and safety of this dipeptidyl peptidase-4 inhibitor in various clinical conditions. Therapy area: Metabolic, Diabetology

Biosimilar is a biologic drug that is structurally and functionally similar to an original drug molecule of biological origin that has already been authorized for use. Generation of evidences for comparing a biosimilar with original biomolecule using direct head-to-head randomized controlled trials can be expensive, time-consuming and laborious. The client wanted a review about the indirect treatment comparison (ITC) for biosimilar that would provide useful evidence for judiciously selecting the best choice of treatment. A well-designed and appropriately conducted ITCs, being increasingly used for biosimilar approval in the EU, can be a valid alternative and means for efficacy and safety evidence generation.

PHYSICIAN'S PERCEPTION MAPPING AND CLINICAL PRACTICE GUIDELINES

Diabetes is a serious health burden and is on the rise across the world. India is no exception with a large population being affected with this condition and newer therapeutic regimes are required for better control. Our client wanted to conduct a survey to understand the view of Indian physicians and endocrinologists regarding the available therapeutic considerations for type 2 diabetes treatment. A questionnaire focusing on issues pertaining to lifestyle intervention prior to initiation of medication was distributed among the physicians working at several primary secondary and tertiary care centers across India. Based on the data from the questionnaires, it was concluded that for newly diagnosed type 2 diabetes, lifestyle intervention was most preferred before pharmacological therapy. Additionally, most physicians preferred metformin as the OHA of initial choice. Drugs of second choice included one of the α-glucosidase inhibitors and DPP4 inhibitor, which were preferred over sulfonylureas.

Combined Hormonal Contraceptives (CHCs) belongs to a group of hormonal contraceptives. CHCs have been successfully used to reduce undesired pregnancies. With this clinical guideline the client wanted to promote awareness among Indian doctors regarding contraception methods and provide an update on the effectiveness and safety of CHC. We obtained clinical evidence from global studies, which was subsequently reviewed by the FOGSI expert committee before finalization of the guidelines. The final guideline addressed issues such as: 1) the unmet need for CHCs, 2) their usage (as contraceptive as well as non-contraceptive), 3) associated side effects, and 4) the importance of structured patient counseling. The guidelines also stressed on the CHC-associated safety concerns including contraception in special situations and provided information on patient counseling tips as well as ways to tailor CHC usage as per the patients’ need.

This guideline was considered the FOGSI Position Statement on the use of Progestogens. Combined Hormonal Contraceptives: Counselling and Use in Clinical Practice.

Venous thromboembolism (VTE) is a global health concern with substantial morbidity and mortality. It is often asymptomatic and under-diagnosed, leading to long-term complications and reduced survival.  VTE has also been identified as an immediate threat to patients undergoing major orthopedic procedures such as total hip arthroplasty (THA) and total knee arthroplasty (TKA). National Orthopedic Advisory Committee meeting was conducted to gain understanding of the clinical relevance of the International VTE prevention guidelines for orthopedic patients in India and to derive expert consensus to enhance optimal implementation of thromboprophylaxis after major orthopedic surgery for Indian population. We helped the client to have guided discussion for better VTE prevention after TKR and THR in Indian patients such as: 1) Thromboprophylactic agents, 2) Minimal duration of thromboprophylaxis, 3) Anticoagulation protocol with neuraxial anesthesia and indwelling epidural catheters, and 4) Bleeding management guidance. The guideline also focused on expert opinion on VTE prevention in patients with renal impairment, bilateral TKR / Revision surgery, mobilization and patient convenience, tolerability and adherence to therapy.

This particular anti-TNF-α factor, is considered effective not only in improving clinical symptoms of psoriasis but also in terms of quality of life. Our client wanted the current evidence from the systematic reviews, post-hoc analyses, registries and real-world data that would represent the associated benefit-risk of this anti-TNF-α factor and other biologics such as anti-T cell agents for psoriasis patients. It was found to be cost-effective and efficacious with no increased incidence of adverse events with escalated dosing. The proven post-marketing safety and efficacy phase, and ease of administration over infliximab are the additional benefits of  the molecule.